WorldWideScience

Sample records for primary mechanism responsible

  1. Oscillatory fluid flow influences primary cilia and microtubule mechanics.

    Science.gov (United States)

    Espinha, Lina C; Hoey, David A; Fernandes, Paulo R; Rodrigues, Hélder C; Jacobs, Christopher R

    2014-07-01

    Many tissues are sensitive to mechanical stimuli; however, the mechanotransduction mechanism used by cells remains unknown in many cases. The primary cilium is a solitary, immotile microtubule-based extension present on nearly every mammalian cell which extends from the basal body. The cilium is a mechanosensitive organelle and has been shown to transduce fluid flow-induced shear stress in tissues, such as the kidney and bone. The majority of microtubules assemble from the mother centriole (basal body), contributing significantly to the anchoring of the primary cilium. Several studies have attempted to quantify the number of microtubules emanating from the basal body and the results vary depending on the cell type. It has also been shown that cellular response to shear stress depends on microtubular integrity. This study hypothesizes that changing the microtubule attachment of primary cilia in response to a mechanical stimulus could change primary cilia mechanics and, possibly, mechanosensitivity. Oscillatory fluid flow was applied to two different cell types and the microtubule attachment to the ciliary base was quantified. For the first time, an increase in microtubules around primary cilia both with time and shear rate in response to oscillatory fluid flow stimulation was demonstrated. Moreover, it is presented that the primary cilium is required for this loading-induced cellular response. This study has demonstrated a new role for the cilium in regulating alterations in the cytoplasmic microtubule network in response to mechanical stimulation, and therefore provides a new insight into how cilia may regulate its mechanics and thus the cells mechanosensitivity. Copyright © 2014 Wiley Periodicals, Inc.

  2. Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptor

    Directory of Open Access Journals (Sweden)

    Hulse Richard P

    2012-06-01

    Full Text Available Abstract Background Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation. Results Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI and the complete Freund’s adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype (WT mice. 7-days after

  3. 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.

  4. Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

    Science.gov (United States)

    Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

    2011-01-01

    Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

  5. Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

    Science.gov (United States)

    Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

    2012-01-01

    Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Abnormal language-related oscillatory responses in primary progressive aphasia

    Directory of Open Access Journals (Sweden)

    A. Kielar

    Full Text Available Patients with Primary Progressive Aphasia (PPA may react to linguistic stimuli differently than healthy controls, reflecting degeneration of language networks and engagement of compensatory mechanisms. We used magnetoencephalography (MEG to evaluate oscillatory neural responses in sentence comprehension, in patients with PPA and age-matched controls. Participants viewed sentences containing semantically and syntactically anomalous words that evoke distinct oscillatory responses. For age-matched controls, semantic anomalies elicited left-lateralized 8–30 Hz power decreases distributed along ventral brain regions, whereas syntactic anomalies elicited bilateral power decreases in both ventral and dorsal regions. In comparison to controls, patients with PPA showed altered patterns of induced oscillations, characterized by delayed latencies and attenuated amplitude, which were correlated with linguistic impairment measured offline. The recruitment of right hemisphere temporo-parietal areas (also found in controls was correlated with preserved semantic processing abilities, indicating that preserved neural activity in these regions was able to support successful semantic processing. In contrast, syntactic processing was more consistently impaired in PPA, regardless of neural activity patterns, suggesting that this domain of language is particularly vulnerable to the neuronal loss. In addition, we found that delayed peak latencies of oscillatory responses were associated with lower accuracy for detecting semantic anomalies, suggesting that language deficits observed in PPA may be linked to delayed or slowed information processing. Keywords: MEG oscillations, Primary progressive aphasia (PPA, Sentence comprehension

  7. 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

  8. Primary atmospheric oxidation mechanism for toluene.

    Science.gov (United States)

    Baltaretu, Cristian O; Lichtman, Eben I; Hadler, Amelia B; Elrod, Matthew J

    2009-01-08

    The products of the primary OH-initiated oxidation of toluene were investigated using the turbulent flow chemical ionization mass spectrometry technique at temperatures ranging from 228 to 298 K. A major dienedial-producing pathway was detected for the first time for toluene oxidation, and glyoxal and methylglyoxal were found to be minor primary oxidation products. The results suggest that secondary oxidation processes involving dienedial and epoxide primary products are likely responsible for previous observations of glyoxal and methylglyoxal products from toluene oxidation. Because the dienedial-producing pathway is a null cycle for tropospheric ozone production and glyoxal and methylglyoxal are important secondary organic aerosol precursors, these new findings have important implications for the modeling of toluene oxidation in the atmosphere.

  9. 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.

  10. 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.

  11. 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

  12. Using realist evaluation to assess primary healthcare teams' responses to intimate partner violence in Spain.

    Science.gov (United States)

    Goicolea, Isabel; Hurtig, Anna-Karin; San Sebastian, Miguel; Marchal, Bruno; Vives-Cases, Carmen

    2015-01-01

    Few evaluations have assessed the factors triggering an adequate health care response to intimate partner violence. This article aimed to: 1) describe a realist evaluation carried out in Spain to ascertain why, how and under what circumstances primary health care teams respond to intimate partner violence, and 2) discuss the strengths and challenges of its application. We carried out a series of case studies in four steps. First, we developed an initial programme theory (PT1), based on interviews with managers. Second, we refined PT1 into PT2 by testing it in a primary healthcare team that was actively responding to violence. Third, we tested the refined PT2 by incorporating three other cases located in the same region. Qualitative and quantitative data were collected and thick descriptions were produced and analysed using a retroduction approach. Fourth, we analysed a total of 15 cases, and identified combinations of contextual factors and mechanisms that triggered an adequate response to violence by using qualitative comparative analysis. There were several key mechanisms -the teams' self-efficacy, perceived preparation, women-centred care-, and contextual factors -an enabling team environment and managerial style, the presence of motivated professionals, the use of the protocol and accumulated experience in primary health care- that should be considered to develop adequate primary health-care responses to violence. The full application of this realist evaluation was demanding, but also well suited to explore a complex intervention reflecting the situation in natural settings. Copyright © 2015 SESPAS. Published by Elsevier Espana. All rights reserved.

  13. Research progress on neural mechanisms of primary insomnia by MRI

    Directory of Open Access Journals (Sweden)

    Man WANG

    2018-04-01

    Full Text Available In recent years, more and more researches focused on the neural mechanism of primary insomnia (PI, especially with the development and application of MRI, and researches of brain structure and function related with primary insomnia were more and more in-depth. According to the hyperarousal hypothesis, there are abnormal structure, function and metabolism under certain brain regions of the cortex and subcortex of primary insomnia patients, including amygdala, hippocampus, cingulate gyrus, insular lobe, frontal lobe and parietal lobe. This paper reviewed the research progress of neural mechanisms of primary insomnia by using MRI. DOI: 10.3969/j.issn.1672-6731.2018.03.003

  14. Neurons in red nucleus and primary motor cortex exhibit similar responses to mechanical perturbations applied to the upper-limb during posture

    Directory of Open Access Journals (Sweden)

    Troy Michael Herter

    2015-04-01

    Full Text Available Primary motor cortex (M1 and red nucleus (RN are brain regions involved in limb motor control. Both structures are highly interconnected with the cerebellum and project directly to the spinal cord, although the contribution of RN is smaller than M1. It remains uncertain whether RN and M1 serve similar or distinct roles during posture and movement. Many neurons in M1 respond rapidly to mechanical disturbances of the limb, but it remains unclear whether RN neurons also respond to such limb perturbations. We have compared discharges of single neurons in RN (n = 49 and M1 (n = 109 of one monkey during a postural perturbation task. Neural responses to whole-limb perturbations were examined by transiently applying (300 ms flexor or extensor torques to the shoulder and/or elbow while the monkeys attempted to maintain a static hand posture. Relative to baseline discharges before perturbation onset, perturbations evoked rapid (<100 ms changes of neural discharges in many RN (28 of 49, 57% and M1 (43 of 109, 39% neurons. In addition to exhibiting a greater proportion of perturbation-related neurons, RN neurons also tended to exhibit higher peak discharge frequencies in response to perturbations than M1 neurons. Importantly, neurons in both structures exhibited similar response latencies and tuning properties (preferred torque directions and tuning widths in joint-torque space. Proximal arm muscles also displayed similar tuning properties in joint-torque space. These results suggest that RN is more sensitive than M1 to mechanical perturbations applied during postural control but both structures may play a similar role in feedback control of posture.

  15. Primary and Secondary Variants of Psychopathy in a Volunteer Sample Are Associated With Different Neurocognitive Mechanisms.

    Science.gov (United States)

    Sethi, Arjun; McCrory, Eamon; Puetz, Vanessa; Hoffmann, Ferdinand; Knodt, Annchen R; Radtke, Spenser R; Brigidi, Bartholomew D; Hariri, Ahmad R; Viding, Essi

    2018-04-12

    Recent work has indicated that there at least two distinct subtypes of psychopathy. Primary psychopathy is characterized by low anxiety and thought to result from a genetic predisposition, whereas secondary psychopathy is characterized by high anxiety and thought to develop in response to environmental adversity. Primary psychopathy is robustly associated with reduced neural activation to others' emotions and, in particular, distress. However, it has been proposed that the secondary presentation has different neurocognitive correlates. Primary (n = 50), secondary (n = 100), and comparison (n = 82) groups were drawn from a large volunteer sample (N = 1444) using a quartile-split approach across psychopathic trait (affective-interpersonal) and anxiety measures. Participants performed a widely utilized emotional face processing task during functional magnetic resonance imaging. The primary group showed reduced amygdala and insula activity in response to fear. The secondary group did not differ from the comparison group in these regions. Instead, the secondary group showed reduced activity compared with the comparison group in other areas, including the superior temporal sulcus/inferior parietal lobe, thalamus, pallidum, and substantia nigra. Both psychopathy groups also showed reduced activity in response to fear in the anterior cingulate cortex. During anger processing, the secondary group exhibited reduced activity in the anterior cingulate cortex compared with the primary group. Distinct neural correlates of fear processing characterize individuals with primary and secondary psychopathy. The reduced neural response to fear that characterizes individuals with the primary variant of psychopathic traits is not observed in individuals with the secondary presentation. The neurocognitive mechanisms underpinning secondary psychopathy warrant further systematic investigation. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. Electromagnet Response Time Tests on Primary CRDM of a Prototype Gen-IV SFR

    International Nuclear Information System (INIS)

    Lee, Jae-Han; Koo, Gyeong-Hoi

    2015-01-01

    This paper identifies the electromagnetic response characteristics of the electromagnet of a primary control rod drive mechanism (CRDM) used for the reactor scram function. The test measures the electromagnet response time required to release an armature from a stator controlled by a loss of an electromagnetic force on an armature after shorting a power supply to an electromagnet coil. These tests are carried out while changing the electromagnet core material, an assist spring, and an armature holding current. The main factors influencing the test parameters on the response are found to be the armature holding current for holding the armature loads, and the material type of the electromagnet cores. The minimum response time is 0.13 seconds in the case of using SS410 material as an armature, while the S10C material as an armature has a response time of 0.21 seconds. Electromagnet response time characteristics from the test results will be evaluated by comparing the precise moving data of an electromagnet armature through the use of a high-speed camera and a potentiometer in the future

  1. Microstructure, mechanical properties, and biological response to functionally graded HA coatings

    International Nuclear Information System (INIS)

    Rabiei, Afsaneh; Blalock, Travis; Thomas, Brent; Cuomo, Jerry; Yang, Y.; Ong, Joo

    2007-01-01

    Hydroxyapatite (HA) [Ca 10 (PO 4 ) 6 (OH) 2 ] is the primary mineral content, representing 43% by weight, of bone. Applying a thin layer of HA, to the surface of a metal implant, can promote osseointegration and increase the mechanical stability of the implant. In this study, a biocompatible coating comprising an HA film with functionally graded crystallinity is being deposited on a heated substrate in an Ion Beam Assisted Deposition (IBAD) system. The microstructure of the film was studied using Transmission Electron Microscopy techniques. Finally, initial cell adhesion and cell differentiation on the coating was evaluated using ATCC CRL 1486 human embryonic palatal mesenchymal cell, an osteoblast precursor cell line. The results have shown superior mechanical properties and biological response to the functionally graded HA film

  2. Fracture mechanics evaluation for at typical PWR primary coolant pipe

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, T. [Kansai Electric Power Company, Osaka (Japan); Shimizu, S.; Ogata, Y. [Mitsubishi Heavy Industries, Ltd., Kobe (Japan)

    1997-04-01

    For the primary coolant piping of PWRs in Japan, cast duplex stainless steel which is excellent in terms of strength, corrosion resistance, and weldability has conventionally been used. The cast duplex stainless steel contains the ferrite phase in the austenite matrix and thermal aging after long term service is known to change its material characteristics. It is considered appropriate to apply the methodology of elastic plastic fracture mechanics for an evaluation of the integrity of the primary coolant piping after thermal aging. Therefore we evaluated the integrity of the primary coolant piping for an initial PWR plant in Japan by means of elastic plastic fracture mechanics. The evaluation results show that the crack will not grow into an unstable fracture and the integrity of the piping will be secured, even when such through wall crack length is assumed to equal the fatigue crack growth length for a service period of up to 60 years.

  3. Fracture mechanics evaluation for at typical PWR primary coolant pipe

    International Nuclear Information System (INIS)

    Tanaka, T.; Shimizu, S.; Ogata, Y.

    1997-01-01

    For the primary coolant piping of PWRs in Japan, cast duplex stainless steel which is excellent in terms of strength, corrosion resistance, and weldability has conventionally been used. The cast duplex stainless steel contains the ferrite phase in the austenite matrix and thermal aging after long term service is known to change its material characteristics. It is considered appropriate to apply the methodology of elastic plastic fracture mechanics for an evaluation of the integrity of the primary coolant piping after thermal aging. Therefore we evaluated the integrity of the primary coolant piping for an initial PWR plant in Japan by means of elastic plastic fracture mechanics. The evaluation results show that the crack will not grow into an unstable fracture and the integrity of the piping will be secured, even when such through wall crack length is assumed to equal the fatigue crack growth length for a service period of up to 60 years

  4. Engineering the Mechanical Properties of Polymer Networks with Precise Doping of Primary Defects.

    Science.gov (United States)

    Chan, Doreen; Ding, Yichuan; Dauskardt, Reinhold H; Appel, Eric A

    2017-12-06

    Polymer networks are extensively utilized across numerous applications ranging from commodity superabsorbent polymers and coatings to high-performance microelectronics and biomaterials. For many applications, desirable properties are known; however, achieving them has been challenging. Additionally, the accurate prediction of elastic modulus has been a long-standing difficulty owing to the presence of loops. By tuning the prepolymer formulation through precise doping of monomers, specific primary network defects can be programmed into an elastomeric scaffold, without alteration of their resulting chemistry. The addition of these monomers that respond mechanically as primary defects is used both to understand their impact on the resulting mechanical properties of the materials and as a method to engineer the mechanical properties. Indeed, these materials exhibit identical bulk and surface chemistry, yet vastly different mechanical properties. Further, we have adapted the real elastic network theory (RENT) to the case of primary defects in the absence of loops, thus providing new insights into the mechanism for material strength and failure in polymer networks arising from primary network defects, and to accurately predict the elastic modulus of the polymer system. The versatility of the approach we describe and the fundamental knowledge gained from this study can lead to new advancements in the development of novel materials with precisely defined and predictable chemical, physical, and mechanical properties.

  5. Primary Frequency Response with Aggregated DERs: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Guggilam, Swaroop S.; Dhople, Sairaj V.; Zhao, Changhong; Dall' Anese, Emiliano; Chen, Yu Christine

    2017-03-03

    Power networks have to withstand a variety of disturbances that affect system frequency, and the problem is compounded with the increasing integration of intermittent renewable generation. Following a large-signal generation or load disturbance, system frequency is arrested leveraging primary frequency control provided by governor action in synchronous generators. In this work, we propose a framework for distributed energy resources (DERs) deployed in distribution networks to provide (supplemental) primary frequency response. Particularly, we demonstrate how power-frequency droop slopes for individual DERs can be designed so that the distribution feeder presents a guaranteed frequency-regulation characteristic at the feeder head. Furthermore, the droop slopes are engineered such that injections of individual DERs conform to a well-defined fairness objective that does not penalize them for their location on the distribution feeder. Time-domain simulations for an illustrative network composed of a combined transmission network and distribution network with frequency-responsive DERs are provided to validate the approach.

  6. Primary lymph node responses to mosquito bites.

    Science.gov (United States)

    Mellink, J J; Vos, B J

    1977-03-29

    Post-auricular lymph node responses and changes in fresh weight of thymus and spleen of hamsters and mice at 4 and 8 days after primary exposure of both ears to 20 bites by the mosquito Aedes aegypti were studied quantitatively. In both hosts lymph node changes characteristic of the development of cell-mediated immune responses and those which are believed to lead to antibody production occurred, with the emphasis on the latter phenomena. No reactions of thymus and spleen were observed. The responses recorded are considered to be immunologically specific. In hamsters, but not in mice, the responses related to humoral sensitization coincided in time to a large extent with those of the cell-mediated immune processes. The stronger humoral responses in mice were probably in the first place the result of the relatively higher dosages applied.

  7. Mechanical Design of the HER Synchrotron Light Monitor Primary Mirror

    Energy Technology Data Exchange (ETDEWEB)

    Daly, Edward F.; /SLAC; Fisher, Alan S.; Kurita, Nadine R.; Langton, J.; /SLAC

    2011-09-14

    This paper describes the mechanical design of the primary mirror that images the visible portion of the synchrotron radiation (SR) extracted from the High Energy Ring (HER) of the PEP-II B-Factory. During off-axis operation, the water-cooled GlidCop mirror is subjected to a heat flux in excess of 2000 W/cm2. When on-axis imaging occurs, the heat flux due to scattered SR, resistive wall losses and Higher-Order-Mode (HOM) heating is estimated at 1 W/cm2. The imaging surface is plated with Electroless Nickel to improve its optical characteristics. The design requirements for the primary mirror are listed and discussed. Calculated mechanical distortions and stresses experienced by the mirror during on-axis and off-axis operation will be presented.

  8. Epigenetic Mechanisms Regulating Adaptive Responses to Targeted Kinase Inhibitors in Cancer.

    Science.gov (United States)

    Angus, Steven P; Zawistowski, Jon S; Johnson, Gary L

    2018-01-06

    Although targeted inhibition of oncogenic kinase drivers has achieved remarkable patient responses in many cancers, the development of resistance has remained a significant challenge. Numerous mechanisms have been identified, including the acquisition of gatekeeper mutations, activating pathway mutations, and copy number loss or gain of the driver or alternate nodes. These changes have prompted the development of kinase inhibitors with increased selectivity, use of second-line therapeutics to overcome primary resistance, and combination treatment to forestall resistance. In addition to genomic resistance mechanisms, adaptive transcriptional and signaling responses seen in tumors are gaining appreciation as alterations that lead to a phenotypic state change-often observed as an epithelial-to-mesenchymal shift or reversion to a cancer stem cell-like phenotype underpinned by remodeling of the epigenetic landscape. This epigenomic modulation driving cell state change is multifaceted and includes modulation of repressive and activating histone modifications, DNA methylation, enhancer remodeling, and noncoding RNA species. Consequently, the combination of kinase inhibitors with drugs targeting components of the transcriptional machinery and histone-modifying enzymes has shown promise in preclinical and clinical studies. Here, we review mechanisms of resistance to kinase inhibition in cancer, with special emphasis on the rewired kinome and transcriptional signaling networks and the potential vulnerabilities that may be exploited to overcome these adaptive signaling changes.

  9. Elastin governs the mechanical response of medial collateral ligament under shear and transverse tensile loading.

    Science.gov (United States)

    Henninger, Heath B; Valdez, William R; Scott, Sara A; Weiss, Jeffrey A

    2015-10-01

    Elastin is a highly extensible structural protein network that provides near-elastic resistance to deformation in biological tissues. In ligament, elastin is localized between and along the collagen fibers and fascicles. When ligament is stretched along the primary collagen axis, elastin supports a relatively high percentage of load. We hypothesized that elastin may also provide significant load support under elongation transverse to the primary collagen axis and shear along the collagen axis. Quasi-static transverse tensile and shear material tests were performed to quantify the mechanical contributions of elastin during deformation of porcine medial collateral ligament. Dose response studies were conducted to determine the level of elastase enzymatic degradation required to produce a maximal change in the mechanical response. Maximal changes in peak stress occurred after 3h of treatment with 2U/ml porcine pancreatic elastase. Elastin degradation resulted in a 60-70% reduction in peak stress and a 2-3× reduction in modulus for both test protocols. These results demonstrate that elastin provides significant resistance to elongation transverse to the collagen axis and shear along the collagen axis while only constituting 4% of the tissue dry weight. The magnitudes of the elastin contribution to peak transverse and shear stress were approximately 0.03 MPa, as compared to 2 MPa for axial tensile tests, suggesting that elastin provides a highly anisotropic contribution to the mechanical response of ligament and is the dominant structural protein resisting transverse and shear deformation of the tissue. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy

    International Nuclear Information System (INIS)

    Dabestani, A.; Child, J.S.; Henze, E.; Perloff, J.K.; Schon, H.; Figueroa, W.G.; Schelbert, H.R.; Thessomboon, S.

    1984-01-01

    M-mode and 2-dimensional echocardiography and gated equilibrium blood pool imaging (rest and exercise) were used in 10 patients with primary hemochromatosis to characterize the spectrum of pathophysiologic abnormalities of the cardiac ventricles and to determine the response to chronic therapeutic phlebotomy. Dilated and restrictive cardiomyopathic patterns were identified in 1 patient each, but our data do not permit conclusions on when in the natural history a given pattern becomes overt. On entry into study, 3 patients had normal ventricles and 7 had ventricular abnormalities on echocardiography and blood pool angiography. In 2 of the latter patients, biventricular dysfunction and increased left ventricular (LV) mass normalized after phlebotomy; 1 patient achieved a normal LV response to exercise. Of the 4 patients with isolated abnormal LV ejection fraction responses to exercise, the EF normalized in 2 after phlebotomy. In 1 patient, isolated right ventricular enlargement and dysfunction (echocardiographic and radionuclide imaging) normalized after phlebotomy. Thus, primary hemochromatosis can effect LV and RV size and function; clinically occult cardiac involvement can be identified by echocardiography and equilibrium blood pool imaging; therapeutic phlebotomy can ameliorate or reverse the deleterious effects of excess cardiac iron deposition which appears to exert its harm, at least in part, by a mechanism other than irreversible connective tissue replacement

  11. Kinetics and mechanism of oxidation of aliphatic primary alcohols by ...

    Indian Academy of Sciences (India)

    Unknown

    Kinetics and mechanism of oxidation of aliphatic primary alcohols by quinolinium bromochromate. SONU SARASWAT, VINITA SHARMA and K K BANERJI*. Department of Chemistry, JNV University, Jodhpur 342 005, India e-mail: banerjikk@rediffmail.com. MS received 4 December 2001; revised 2 November 2002.

  12. Developing a response to family violence in primary health care: the New Zealand experience.

    Science.gov (United States)

    Gear, Claire; Koziol-McLain, Jane; Wilson, Denise; Clark, Faye

    2016-08-20

    Despite primary health care being recognised as an ideal setting to effectively respond to those experiencing family violence, responses are not widely integrated as part of routine health care. A lack of evidence testing models and approaches for health sector integration, alongside challenges of transferability and sustainability, means the best approach in responding to family violence is still unknown. The Primary Health Care Family Violence Responsiveness Evaluation Tool was developed as a guide to implement a formal systems-led response to family violence within New Zealand primary health care settings. Given the difficulties integrating effective, sustainable responses to family violence, we share the experience of primary health care sites that embarked on developing a response to family violence, presenting the enablers, barriers and resources required to maintain, progress and sustain family violence response development. In this qualitative descriptive study data were collected from two sources. Firstly semi-structured focus group interviews were conducted during 24-month follow-up evaluation visits of primary health care sites to capture the enablers, barriers and resources required to maintain, progress and sustain a response to family violence. Secondly the outcomes of a group activity to identify response development barriers and implementation strategies were recorded during a network meeting of primary health care professionals interested in family violence prevention and intervention; findings were triangulated across the two data sources. Four sites, representing three PHOs and four general practices participated in the focus group interviews; 35 delegates from across New Zealand attended the network meeting representing a wider perspective on family violence response development within primary health care. Enablers and barriers to developing a family violence response were identified across four themes: 'Getting started', 'Building effective

  13. Mechanical touch responses of Arabidopsis TCH1-3 mutant roots on inclined hard-agar surface

    Science.gov (United States)

    Zha, Guodong; Wang, Bochu; Liu, Junyu; Yan, Jie; Zhu, Liqing; Yang, Xingyan

    2016-01-01

    The gravity-induced mechanical touch stimulus can affect plant root architecture. Mechanical touch responses of plant roots are an important aspect of plant root growth and development. Previous studies have reported that Arabidopsis TCH1-3 genes are involved in mechano-related events, how-ever, the physiological functions of TCH1-3 genes in Arabidopsis root mechanoresponses remain unclear. In the present study, we applied an inclined hard agar plate method to produce mechanical touch stimulus, and provided evidence that altered mechanical environment could influence root growth. Furthermore, tch1-3 Arabidopsis mutants were investigated on inclined agar surfaces to explore the functions of TCH1-3 genes on Arabidopsis root mechanoresponses. The results showed that two tch2 mutants, cml24-2 and cml24-4, exhibited significantly reduced root length, biased skewing, and decreased density of lateral root. In addition, primary root length and density of lateral root of tch3 (cml12-2) was significantly decreased on inclined agar surfaces. This study indicates that the tch2 and tch3 mutants are hypersensitive to mechanical touch stimulus, and TCH2 (CML24-2 and CML24-4) and TCH3 (CML12-2) genes may participate in the mechanical touch response of Arabidopsis roots.

  14. 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

  15. Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences.

    Science.gov (United States)

    Franzen-Röhl, Elisabeth; Schepis, Danika; Atterfelt, Fredrik; Franck, Kristina; Wikström, Arne; Liljeqvist, Jan-Åke; Bergström, Tomas; Aurelius, Elisabeth; Kärre, Klas; Berg, Louise; Gaines, Hans

    2017-05-01

    During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. HSV-specific interleukin(Il)-4 and Il-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Regulation of primary cytotoxic T lymphocyte responses generated during mixed leukocyte culture with H-2d identical Qa-1-disparate cells

    International Nuclear Information System (INIS)

    Huston, D.P.; Tavana, G.; Rich, R.R.; Gressens, S.E.

    1986-01-01

    Cytotoxic lymphocyte (CTL) responses are not usually generated during primary mixed leukocyte culture (MLC) with H-2 identical cells. Thus NZB mice are unusual in that their spleen cells do mount CTL responses during primary MLC with H-2d identical stimulator cells; the predominant target antigen for these NZB responses is Qa-1b. Considering the numerous immunoregulatory defects in NZB mice, we postulated that these NZB anti-Qa-1 primary CTL responses were due to an abnormality in T suppressor cell activity. Cellular interactions capable of suppressing NZB anti-Qa-1 primary CTL responses were investigated by using one-way and two-way MLC with spleen cells from NZB mice and other H-2d strains. Although H-2d identical one-way MLC with the use of NZB responders resulted in substantial CTL responses, only minimal CTL responses were detected from two-way MLC with the use of NZB spleen cells plus nonirradiated spleen cells from other H-2d mice. Thus the presence of non-NZB spleen cells in the two-way H-2d identical MLC prevented the generation of NZB CTL. Noncytotoxic mechanisms were implicated in the suppression of the NZB CTL responses during two-way MLC, because only minimal CTL activity was generated when NZB spleen cells were cultured with semiallogeneic, H-2d identical (e.g., NZB X BALB) F1 spleen cells. The observed suppression could be abrogated with as little as 100 rad gamma-irradiation to the non-NZB spleen cells. The phenotype of these highly radiosensitive spleen cells was Thy-1+, Lyt-1+, Lyt-2-, L3T4+. The functional presence of these cells in the spleens of semiallogeneic, H-2d identical F1 mice indicated that their deficiency in NZB mice was a recessive trait. These data suggest that NZB mice lack an L3T4+ cell present in the spleens of normal mice that is capable of suppressing primary anti-Qa-1 CTL responses

  17. Development of new design mechanical seal tester for Primary Loop Recirculation Pump (PLR Pump)

    International Nuclear Information System (INIS)

    Fukushima, Naoki; Koshiba, Koremutsu

    1995-01-01

    The mechanical seal for a Primary Loop Recirculation Pump (PLR Pump) is an important part of a BWR plant. This study describes a new mechanical seal tester developed to certify mechanical seal performance before installation in a PLR Pump on site. (author)

  18. 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...

  19. Canada’s response to refugees at the primary health care level

    Directory of Open Access Journals (Sweden)

    Kevin Pottie

    2018-03-01

    Full Text Available Responsive primary health care systems and services must be at once complex and nimble. Policy makers may wish to believe that existing health systems effectively care for all populations equally, including refugees. However, we know that refugees may require a health equity approach: an approach where all levels of government, all types of health practitioners, and even the public sector, participate to ensure access to effective primary health care. This article outlines some of Canada’s healthcare responses for refugee populations. We provide field examples and guidelines that demonstrate responses, as well as ongoing inconsistencies and limitations. Refugee-receiving countries such as Australia, the US and Canada all have stories of success in resettlement and health systems. This article will focus on Canada.

  20. Characterization of the CD8+ T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

    International Nuclear Information System (INIS)

    Lukens, Michael V.; Claassen, Erwin A.W.; Graaff, Patricia M.A. de; Dijk, Mariska E.A. van; Hoogerhout, Peter; Toebes, Mireille; Schumacher, Ton N.; Most, Robbert G. van der; Kimpen, Jan L.L.; Bleek, Grada M. van

    2006-01-01

    The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4 + and CD8 + T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8 + T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes were recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8 + T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice

  1. Primary Structure and Mechanical Properties of AlSi2 Alloy Continuous Ingots

    Directory of Open Access Journals (Sweden)

    Wróbel T.

    2017-06-01

    Full Text Available The paper presents the research results of horizontal continuous casting of ingots of aluminium alloy containing 2% wt. silicon (AlSi2. Together with the casting velocity (velocity of ingot movement we considered the influence of electromagnetic stirring in the area of the continuous casting mould on refinement of the ingot’s primary structure and their selected mechanical properties, i.e. tensile strength, yield strength, hardness and elongation. The effect of primary structure refinement and mechanical properties obtained by electromagnetic stirring was compared with refinement obtained by using traditional inoculation, which consists in introducing additives, i.e. Ti, B and Sr, to the metal bath. On the basis of the obtained results we confirmed that inoculation done by electromagnetic stirring in the range of the continuous casting mould guarantees improved mechanical properties and also decreases the negative influence of casting velocity, thus increasing the structure of AlSi2 continuous ingots.

  2. A Simple Network Architecture Accounts for Diverse Reward Time Responses in Primary Visual Cortex.

    Science.gov (United States)

    Huertas, Marco A; Hussain Shuler, Marshall G; Shouval, Harel Z

    2015-09-16

    Many actions performed by animals and humans depend on an ability to learn, estimate, and produce temporal intervals of behavioral relevance. Exemplifying such learning of cued expectancies is the observation of reward-timing activity in the primary visual cortex (V1) of rodents, wherein neural responses to visual cues come to predict the time of future reward as behaviorally experienced in the past. These reward-timing responses exhibit significant heterogeneity in at least three qualitatively distinct classes: sustained increase or sustained decrease in firing rate until the time of expected reward, and a class of cells that reach a peak in firing at the expected delay. We elaborate upon our existing model by including inhibitory and excitatory units while imposing simple connectivity rules to demonstrate what role these inhibitory elements and the simple architectures play in sculpting the response dynamics of the network. We find that simply adding inhibition is not sufficient for obtaining the different distinct response classes, and that a broad distribution of inhibitory projections is necessary for obtaining peak-type responses. Furthermore, although changes in connection strength that modulate the effects of inhibition onto excitatory units have a strong impact on the firing rate profile of these peaked responses, the network exhibits robustness in its overall ability to predict the expected time of reward. Finally, we demonstrate how the magnitude of expected reward can be encoded at the expected delay in the network and how peaked responses express this reward expectancy. Heterogeneity in single-neuron responses is a common feature of neuronal systems, although sometimes, in theoretical approaches, it is treated as a nuisance and seldom considered as conveying a different aspect of a signal. In this study, we focus on the heterogeneous responses in the primary visual cortex of rodents trained with a predictable delayed reward time. We describe under what

  3. 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

  4. Conceptual Design on Primary Control Rod Drive Mechanism of a Prototype Gen-IV SFR

    International Nuclear Information System (INIS)

    Lee, Jae Han; Koo, Gyeong Hoi

    2013-01-01

    This paper describes the key concept of the drive mechanism, and suggests a required motor power and reducer gears to meet the functional design requirements, and a seismic response analysis of CRDM housing is performed to check its structural integrity. An AC servo motor is selected as a CRA driving power because it uses permanent magnets and is brushless type while DC motor needs a brush and a coil rotates. The control shim motor size is constrained by a housing diameter of 250mm. The driving system has several design requirements. To calculate the motor power, the drive shaft torque is needed. One part of the drive shaft has a lead screw, driving by a ball-nut. The ball screw driver torque (Tr) is calculated by some equations as follow; A servo motor with a nominal power of 100W, a nominal torque of 0.32 N-m (max. 0.48N-m) is selected considering a safety margin. Its diameter is about 50mm. The fast drive-in motor needs a strong power to insert enforcedly the stuck CRA into core within a required time. The motor sizes are calculated by the same procedure. The diameters are in the range of 80mm to 110mm by the insertion time (10 ∼ 24 seconds). The prototype Gen-IV SFR (sodium-cooled Fast Reactor) is of 150MWe capacity. The reactor has six primary control rod assemblies(CRAs). The primary control rod is used for power control, burn-up compensation and reactor shutdown in response to demands from the plant control or protection systems. The control rod drive mechanism (CRDM) consists of the drive motor assembly, the driveline, and its housing. The driveline consists of three concentric members of a drive shaft, a tension tube, and a position indicator rod, and it connects the drive motor assembly to the CRA. Main issue is that these many driving parts shall be enclosed within a limited housing diameter because the available pitch of CRDMs is limited by 300mm

  5. Conceptual Design on Primary Control Rod Drive Mechanism of a Prototype Gen-IV SFR

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Han; Koo, Gyeong Hoi [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    This paper describes the key concept of the drive mechanism, and suggests a required motor power and reducer gears to meet the functional design requirements, and a seismic response analysis of CRDM housing is performed to check its structural integrity. An AC servo motor is selected as a CRA driving power because it uses permanent magnets and is brushless type while DC motor needs a brush and a coil rotates. The control shim motor size is constrained by a housing diameter of 250mm. The driving system has several design requirements. To calculate the motor power, the drive shaft torque is needed. One part of the drive shaft has a lead screw, driving by a ball-nut. The ball screw driver torque (Tr) is calculated by some equations as follow; A servo motor with a nominal power of 100W, a nominal torque of 0.32 N-m (max. 0.48N-m) is selected considering a safety margin. Its diameter is about 50mm. The fast drive-in motor needs a strong power to insert enforcedly the stuck CRA into core within a required time. The motor sizes are calculated by the same procedure. The diameters are in the range of 80mm to 110mm by the insertion time (10 ∼ 24 seconds). The prototype Gen-IV SFR (sodium-cooled Fast Reactor) is of 150MWe capacity. The reactor has six primary control rod assemblies(CRAs). The primary control rod is used for power control, burn-up compensation and reactor shutdown in response to demands from the plant control or protection systems. The control rod drive mechanism (CRDM) consists of the drive motor assembly, the driveline, and its housing. The driveline consists of three concentric members of a drive shaft, a tension tube, and a position indicator rod, and it connects the drive motor assembly to the CRA. Main issue is that these many driving parts shall be enclosed within a limited housing diameter because the available pitch of CRDMs is limited by 300mm.

  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. Characterization of cellular immune response and innate immune signaling in human and nonhuman primate primary mononuclear cells exposed to Burkholderia mallei.

    Science.gov (United States)

    Alam, Shahabuddin; Amemiya, Kei; Bernhards, Robert C; Ulrich, Robert G; Waag, David M; Saikh, Kamal U

    2015-01-01

    Burkholderia pseudomallei infection causes melioidosis and is often characterized by severe sepsis. Although rare in humans, Burkholderia mallei has caused infections in laboratory workers, and the early innate cellular response to B. mallei in human and nonhuman primates has not been characterized. In this study, we examined the primary cellular immune response to B. mallei in PBMC cultures of non-human primates (NHPs), Chlorocebus aethiops (African Green Monkeys), Macaca fascicularis (Cynomolgus macaque), and Macaca mulatta (Rhesus macaque) and humans. Our results demonstrated that B. mallei elicited strong primary pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, and IL-6) equivalent to the levels of B. pseudomallei in primary PBMC cultures of NHPs and humans. When we examined IL-1β and other cytokine responses by comparison to Escherichia coli LPS, African Green Monkeys appears to be most responsive to B. mallei than Cynomolgus or Rhesus. Characterization of the immune signaling mechanism for cellular response was conducted by using a ligand induced cell-based reporter assay, and our results demonstrated that MyD88 mediated signaling contributed to the B. mallei and B. pseudomallei induced pro-inflammatory responses. Notably, the induced reporter activity with B. mallei, B. pseudomallei, or purified LPS from these pathogens was inhibited and cytokine production was attenuated by a MyD88 inhibitor. Together, these results show that in the scenario of severe hyper-inflammatory responses to B. mallei infection, MyD88 targeted therapeutic intervention may be a successful strategy for therapy. Published by Elsevier Ltd.

  8. Engine Tune-Up Service. Unit 3: Primary Circuit. Student Guide. Automotive Mechanics Curriculum.

    Science.gov (United States)

    Bacon, E. Miles

    This student guide is for Unit 3, Primary Circuit, in the Engine Tune-Up Service portion of the Automotive Mechanics Curriculum. It deals with how to test the primary ignition circuit. A companion review exercise book and posttests are available separately as CE 031 212-213. An introduction tells how this unit fits into the total tune-up service,…

  9. Relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma)

    International Nuclear Information System (INIS)

    Higashi, Kotaro; Takase, Shuko; Ohguchi, Manabu; Seki, Hiroyasu; Okimura, Tetsuro; Miyamura, Toshio; Yamamoto, Itaru; Rikimaru, Shigeho.

    1992-01-01

    This investigation was undertaken to evaluate the relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma), Ga-67 uptake of tumor was estimated on 16 patients with untreated primary lung cancer (squamous cell carcinoma). Ga-67 uptake was then compared with the response to radiation therapy (tumor reduction ratio). There was statistically significant inverse correlation between Ga-67 uptake and response to radiation therapy (r=-0.701, p<0.01). The fewer the Ga-67 accumulation in the tumor, the more effective radiotherapy in reducing tumor size. In conclusion, Ga-67 scintigraphy appears to be able to predict the response of primary lung cancer (squamous cell carcinoma) to radiation therapy. (author)

  10. 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.

  11. The mechanism for the primary biological effects of ionizing radiation

    International Nuclear Information System (INIS)

    Byakov, Vsevolod M; Stepanov, Sergei V

    2006-01-01

    The primary biological response of living organisms to the passage of fast charged particles is traditionally believed to be dominated by the chemical reactions of the radical products from the radiolysis of cellular water (OH, H, e aq - , O 2 - , H 2 O 2 ) and by the bioradicals that they produce (and which can also result from the direct electronic activation of biomolecules). This understanding has provided insight into how ionizing radiations affect biological systems and, most importantly, what radioprotection and radiosensibilizing effects are produced by chemical compounds introduced into an organism. However, a number of key radiobiological facts remain unexplained by the current theory, stimulating a search for other biologically active factors that may be triggered by radiation. This review examines a fact that is usually ignored in discussing the biological impact of ionizing radiation: the local increase in acidity in the water solution along the track of a charged particle. The acidity in the track is very different from its value for cellular water in a living organism. Biological processes are well-known to be highly sensitive to changes in the environmental acidity. It seems that the biological impact of ionizing radiations is dominated not by the water radiolysis products (mostly radicals) listed above but particles of a different nature, hydroxonium ions H 3 O + , where the term hydroxonium refer to protonated water molecules. This modification of the mechanism of primary radiobiological effects is in good agreement with experimental data. In particular, the extremal dependence of the relative biological efficiency (RBE) of radiations on their ionizing energy losses is accounted for in quantitative terms, as is the increase in the RBE in the relativistic energy range. (reviews of topical problems)

  12. 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

  13. Mechanism of the N-Hydroxylation of Primary and Secondary Amines by Cytochrome P450

    DEFF Research Database (Denmark)

    Seger, Signe T.; Rydberg, Patrik; Olsen, Lars

    2015-01-01

    Cytochrome P450 enzymes (CYPs) metabolize alkyl- and arylamines, generating several different products. For the primary and secondary amines, some of these reactions result in hydroxylated amines, which may be toxic. Thus, when designing new drugs containing amine groups, it is important to be able...... to predict if a given compound will be a substrate for CYPs, in order to avoid toxic metabolites, and hence to understand the mechanism that is utilized by CYPs. Two possible mechanisms, for the N-hydroxylation of primary and secondary amines mediated by CYPs, are studied by density functional theory (DFT...

  14. Cellular responses in primary epidermal cultures from oncorhynchus mykiss following the combined exposure of ionising radiation and a heavy metal

    International Nuclear Information System (INIS)

    Lyng, F.M.; Ni Shuilleabhain, S.; Davoren, M.

    2004-01-01

    Mechanisms of toxicant action on biological systems are difficult to identify when more than one contaminant is involved due to potential synergistic and antagonistic effects. There is a general paucity of research into the effect of radiation exposure in tandem with common environmental contaminants due to the inherent difficulties involved. In vitro cell cultures are particularly suited to the study of toxic mechanisms due to their proximity to toxic modes of action and the absence of the multiple defence mechanisms present in intact organisms. Primary cell cultures are particularly beneficial in this area of research as they still maintain many of their tissue specific functions. The objective of this study was to distinguish different mechanisms of cell death (growth arrest, apoptosis, primary and secondary necrosis and proliferation), following combination exposure to ionising radiation and a heavy metal (ZnCl 2 ). The model system employed was a primary cell culture of rainbow trout (Oncorhynchus mykiss) epidermal tissue which has been previously used to study the effects of various environmental agents in this laboratory. Apoptosis and necrosis were quantified morphologically while proliferation was assessed immuno-cyto-chemically using an anti PCNA (proliferating cell nuclear antigen) antibody. While radiation doses up to and including 10 Gy had no effect on growth, exposure to ZnCl 2 produced a significant dose dependent reduction in growth (10, 50, 75, 100 and 200 ppm ZnCl 2 ). Preliminary results indicate no significant effect on growth following a combined exposure of 5 Gy + 50 ppm ZnCl 2 . These results may have important implications for understanding the mechanisms underlying cellular responses to multiple contaminant exposures. (author)

  15. 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)

  16. 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.

  17. 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.

  18. 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.

  19. Study on the primary mechanism of uranium biosorption by rhodotorula glutinis

    International Nuclear Information System (INIS)

    Bai Jing; Zhang Li'na; Fan Fangli; Lin Maosheng; Ding Huajie; Qin Zhi

    2008-01-01

    In this paper, the primary mechanism of uranium biosorption by Rhodotorula glutinis was studied using SEM and FTIR. Obvious changes were observed in the biomass SEM picture before and after uranium adsorption, and the peak of UO 2 at wave number of 904 cm -1 was detected by FTIR, indicated that uranium was really absorbed to Rhodotorula glutinis. (authors)

  20. Investigation of the conservatism associated with different combinations between primary and secondary piping responses

    International Nuclear Information System (INIS)

    Wang, Y.K.; Subudhi, M.; Bezler, P.

    1983-01-01

    This report includes the findings of an investigation of the conservatism associated with different combinations between the primary and secondary stress components for piping systems under dynamic loading, such as in an earthquake event. The primary stresses are induced by piping response to its mass inertia effects. The secondary stresses are induced by relative displacements of piping supports. The study involves an independnent time history analysis of several typical piping models to predict a best estimate of the actual dynamic and pseudo-static pipe responses to an earthquake. These piping systems are also analyzed using the response spectrum method to obtain the maximum primary stress components. Secondary stresses are next calculated by performing a set of static analyses which provide the worst stress condition. The two components are then combined by both SRSS and absolute sum methods as the results are compared with time history solutions. It is found that the SRSS combination of the primary and secondary stress components yield acceptable results provided the secondary stress component is calculated in the most unfavorable phasing relationship among displacements of piping supports

  1. Primary School Pupils' Response to Audio-Visual Learning Process in Port-Harcourt

    Science.gov (United States)

    Olube, Friday K.

    2015-01-01

    The purpose of this study is to examine primary school children's response on the use of audio-visual learning processes--a case study of Chokhmah International Academy, Port-Harcourt (owned by Salvation Ministries). It looked at the elements that enhance pupils' response to educational television programmes and their hindrances to these…

  2. Genetic mechanisms leading to primary amenorrhea in balanced X-autosome translocations.

    Science.gov (United States)

    Moysés-Oliveira, Mariana; Guilherme, Roberta Dos Santos; Dantas, Anelisa Gollo; Ueta, Renata; Perez, Ana Beatriz; Haidar, Mauro; Canonaco, Rosane; Meloni, Vera Ayres; Kosyakova, Nadezda; Liehr, Thomas; Carvalheira, Gianna Maria; Melaragno, Maria Isabel

    2015-05-01

    To map the X-chromosome and autosome breakpoints in women with balanced X-autosome translocations and primary amenorrhea, searching candidate genomic loci for female infertility. Retrospective and case-control study. University-based research laboratory. Three women with balanced X-autosome translocation and primary amenorrhea. Conventional cytogenetic methods, genomic array, array painting, fluorescence in situ hybridization, and quantitative reverse transcription-polymerase chain reaction. Karyotype, copy number variation, breakpoint mapping, and gene expression levels. All patients presented with breakpoints in the Xq13q21 region. In two patients, the X-chromosome breakpoint disrupted coding sequences (KIAA2022 and ZDHHC15 genes). Although both gene disruptions caused absence of transcription in peripheral blood, there is no evidence that supports the involvement of these genes with ovarian function. The ZDHHC15 gene belongs to a conserved syntenic region that encompasses the FGF16 gene, which plays a role in female germ line development. The break in the FGF16 syntenic block may have disrupted the interaction between the FGF16 promoter and its cis-regulatory element. In the third patient, although both breakpoints are intergenic, a gene that plays a role in the DAX1 pathway (FHL2 gene) flanks distally the autosome breakpoint. The FHL2 gene may be subject to position effect due to the attachment of an autosome segment in Xq21 region. The etiology of primary amenorrhea in balanced X-autosome translocation patients may underlie more complex mechanisms than interruption of specific X-linked candidate genes, such as position effect. The fine mapping of the rearrangement breakpoints may be a tool for identifying genetic pathogenic mechanisms for primary amenorrhea. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. The responses of three nigerian indigenous goat breeds to primary ...

    African Journals Online (AJOL)

    Responses of three Nigerian breeds of goat; Red Sokoto (RS), West African Dwarf (WAD) and Sahel White (SW) were investigated following primary and secondary experimental infections ... On day 42 post infection, (n=12) goats, (4 per breed) of the infected animals were humanely euthanized and worm count determined.

  4. Helicobacter pylori Type IV Secretion System and Its Adhesin Subunit, CagL, Mediate Potent Inflammatory Responses in Primary Human Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Mona Tafreshi

    2018-02-01

    Full Text Available The Gram-negative bacterium, Helicobacter pylori, causes chronic gastritis, peptic ulcers, and gastric cancer in humans. Although the gastric epithelium is the primary site of H. pylori colonization, H. pylori can gain access to deeper tissues. Concurring with this notion, H. pylori has been found in the vicinity of endothelial cells in gastric submucosa. Endothelial cells play crucial roles in innate immune response, wound healing and tumorigenesis. This study examines the molecular mechanisms by which H. pylori interacts with and triggers inflammatory responses in endothelial cells. We observed that H. pylori infection of primary human endothelial cells stimulated secretion of the key inflammatory cytokines, interleukin-6 (IL-6 and interleukin-8 (IL-8. In particular, IL-8, a potent chemokine and angiogenic factor, was secreted by H. pylori-infected endothelial cells to levels ~10- to 20-fold higher than that typically observed in H. pylori-infected gastric epithelial cells. These inflammatory responses were triggered by the H. pylori type IV secretion system (T4SS and the T4SS-associated adhesin CagL, but not the translocation substrate CagA. Moreover, in contrast to integrin α5β1 playing an essential role in IL-8 induction by H. pylori upon infection of gastric epithelial cells, both integrin α5β1 and integrin αvβ3 were dispensable for IL-8 induction in H. pylori-infected endothelial cells. However, epidermal growth factor receptor (EGFR is crucial for mediating the potent H. pylori-induced IL-8 response in endothelial cells. This study reveals a novel mechanism by which the H. pylori T4SS and its adhesin subunit, CagL, may contribute to H. pylori pathogenesis by stimulating the endothelial innate immune responses, while highlighting EGFR as a potential therapeutic target for controlling H. pylori-induced inflammation.

  5. 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...

  6. Responses of primary producers to mouth closure in the temporarily ...

    African Journals Online (AJOL)

    Low river inflow conditions during 2009/2010 resulted in the mouth of the Great Brak Estuary remaining closed for almost two years. The low water level in Wolwedans Dam resulted in no annual environmental flow releases being made, causing mouth closure. The response of primary producers to this prolonged period of ...

  7. 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.

  8. Primary immunodeficiencies: a pictorial immunology primer for radiologists

    International Nuclear Information System (INIS)

    Manson, D.E.; Sikka, S.; Reid, B.; Roifman, C.

    2000-01-01

    The immune response constitutes a complex array of interconnecting pathways and mechanisms that result in a sophisticated series of communicative reactions designed to protect against foreign substances. Recent advances in immunologic investigations have begun to unlock many of the previous mysteries underlying the body's defense mechanisms. The complexities of organ transplantation, the isolation of organisms that selectively impair the immune system, and the widespread use of sophisticated anti-neoplastic therapies have necessitated a more comprehensive understanding of underlying immune mechanisms by all physicians. This review presents a simplified view of the development of the immune response. We present strategic examples of primary (i.e., congenital) disorders of immune function to create a framework to understand the major mechanisms that constitute the various ''arms'' of the immune system. It is sometimes easier to understand complex mechanisms when one sees how disease processes interfere with these mechanisms. We have excluded many of the more detailed and complicated mechanisms involved in the immune response in an effort to maintain simplicity

  9. Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response

    Directory of Open Access Journals (Sweden)

    Hemantkumar Chavan

    2017-01-01

    Full Text Available Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.

  10. 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.

  11. 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.

  12. 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

  13. Mechanical and IL-1β Responsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4

    Directory of Open Access Journals (Sweden)

    Xu Yang

    2016-03-01

    Full Text Available Mechanical stress plays an important role in the initiation and progression of osteoarthritis. Studies show that excessive mechanical stress can directly damage the cartilage extracellular matrix and shift the balance in chondrocytes to favor catabolic activity over anabolism. However, the underlying mechanism remains unknown. MicroRNAs (miRNAs are emerging as important regulators in osteoarthritis pathogenesis. We have found that mechanical loading up-regulated microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte differentiation. Here, we explored the role of the mechanical responsive microRNA miR-365 in pathogenesis of osteoarthritis (OA. We found that miR-365 was up-regulated by cyclic loading and IL-1β stimulation in articular chondrocytes through a mechanism that involved the transcription factor NF-κB. miR-365 expressed significant higher level in rat anterior cruciate ligament (ACL surgery induced OA cartilage as well as human OA cartilage from primary OA patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes increases gene expression of matrix degrading enzyme matrix metallopeptidase 13 (MMP13 and collagen type X (Col X. The increase in miR-365 expression in OA cartilage and in response to IL-1 may contribute to the abnormal gene expression pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1β induced MMP13 and Col X gene expression. We further showed histone deacetylase 4 (HDAC4 is a direct target of miR-365, which mediates mechanical stress and inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of mechanical stress and pro-inflammatory responses, which contributes cartilage catabolism. Manipulation of the expression of miR-365 in articular chondrocytes by miR-365 inhibitor may be a potent therapeutic target for the prevention and treatment of osteoarthritis.

  14. 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.

  15. 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...

  16. Responsibility for Financial Management in Primary Schools: Evidence from an English Local Authority

    Science.gov (United States)

    Fitzgerald, Sarah; Drake, Julie

    2013-01-01

    Financial management in primary schools has changed in the UK with the introduction of the Schools Financial Value Standard (SFVS). There is increasing delegation of financial responsibility to the management team in the school, increasing the role of the head teacher and the governing body as part of overall responsibility for the strategic…

  17. The role of the primary care team in the rapid response system.

    Science.gov (United States)

    O'Horo, John C; Sevilla Berrios, Ronaldo A; Elmer, Jennifer L; Velagapudi, Venu; Caples, Sean M; Kashyap, Rahul; Jensen, Jeffrey B

    2015-04-01

    The purpose of the study is to evaluate the impact of primary service involvement on rapid response team (RRT) evaluations. The study is a combination of retrospective chart review and prospective survey-based evaluation. Data included when and where the activations occurred and the patient's code status, primary service, and ultimate disposition. These data were correlated with survey data from each event. A prospective survey evaluated the primary team's involvement in decision making and the overall subjective quality of the interaction with primary service through a visual analog scale. We analyzed 4408 RRTs retrospectively and an additional 135 prospectively. The primary team's involvement by telephone or in person was associated with significantly more transfers to higher care levels in retrospective (P team involvement, with more frequent changes seen in the retrospective analysis (P = .01). Subjective ratings of communication by the RRT leader were significantly higher when the primary service was involved (P team involvement influences RRT activation processes of care. The RRT role should be an adjunct to, but not a substitute for, an engaged and present primary care team. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The responsibility continuum: never primary, coresident and caregiver--heterogeneity in the African-American grandmother experience.

    Science.gov (United States)

    Lee, Rosalyn D; Ensminger, Margaret E; LaVeist, Thomas A

    2005-01-01

    This article examines diversity among 542 African-American grandmothers from the Woodlawn Longitudinal Study. Women were categorized on the basis of their household composition, degree of care provided to grandchildren, and status of primary caregiver to grandchildren during lifetime. Overall, 67.7% of the sample engaged in parenting and exchange behaviors at high or moderate levels. Twenty-seven percent of the sample coresided with and provided care to grandchildren, 28% did not coreside but had been primary caregivers in the past, and 45% did not coreside and had never been primarily responsible for a grandchild. Heterogeneity was found among seven grandmother types on economic measures, life events, and grandchild characteristics. Grandmothers with earlier primary responsibility and those currently in homes of three or more generations were associated with poor outcomes. Policy and practice can be informed by additional research on status, context, and timing of assumption of responsibilities for grandchildren.

  19. 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

  20. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes.

    Science.gov (United States)

    Deren, Matthew E; Yang, Xu; Guan, Yingjie; Chen, Qian

    2016-02-04

    Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88) siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation) of ATDC5 cells in three-dimensional (3D) culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II), hypertrophic chondrocyte marker Type X collagen (Col X), and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2). The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes.

  1. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes

    Directory of Open Access Journals (Sweden)

    Matthew E. Deren

    2016-02-01

    Full Text Available Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88 siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation of ATDC5 cells in three-dimensional (3D culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II, hypertrophic chondrocyte marker Type X collagen (Col X, and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2. The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes.

  2. 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.

  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. 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...

  5. Suppression of in vitro primary immune response by L1210 cells and their culture supernatant: evidence for cytotoxic effects

    International Nuclear Information System (INIS)

    Huget, R.P.; Flad, H.D.; Opitz, H.G.

    1977-01-01

    L1210 cells and their culture supernatants were found to inhibit the generation of PFC in the in vitro primary immune response of spleen cells to SRBC. As few as 1 percent of L1210 cells and 1 percent of culture fluid were inhibitory. Inhibition of DNA or protein synthesis of L1210 cells did not abolish their immunosuppressive activity, excluding exhaustion of culture medium as a possible mechanism of inhibition of PFC. Heating of the supernatant completely abrogated the suppressive effect and resulted in a marked increase of PFC. Daily evaluation of cell viability in the cultures revealed that, in the presence of L1210 and supernatants, the fraction of surviving cells is markedly reduced. We conclude that a direct cytotoxic effect on splenic lymphocytes and macrophages is the predominant immunosuppressive mechanism of L1210 cells and their culture supernatants

  6. A realist evaluation of social prescribing: an exploration into the context and mechanisms underpinning a pathway linking primary care with the voluntary sector.

    Science.gov (United States)

    Bertotti, Marcello; Frostick, Caroline; Hutt, Patrick; Sohanpal, Ratna; Carnes, Dawn

    2018-05-01

    This article adopts a realist approach to evaluate a social prescribing pilot in the areas of Hackney and City in London (United Kingdom). It unpacks the contextual factors and mechanisms that influenced the development of this pilot for the benefits of GPs, commissioners and practitioners, and reflects on the realist approach to evaluation as a tool for the evaluation of health interventions. Primary care faces considerable challenges including the increase in long-term conditions, GP consultation rates, and widening health inequalities. With its emphasis on linking primary care to non-clinical community services via a social prescribing coordinator (SPC), some models of social prescribing could contribute to reduce the burden on primary care, tackle health inequalities and encourage people to make greater use of non-clinical forms of support. This realist analysis was based on qualitative interviews with users, commissioners, a GP survey, focus groups and learning events to explore stakeholders' experience. To enable a detailed analysis, we adapted the realist approach by subdividing the social prescribing pathway into stages, each with contextual factors, mechanisms and outcomes. SPCs were pivotal to the effective functioning of the social prescribing service and responsible for the activation and initial beneficial impact on users. Although social prescribing shows significant potential for the benefit of patients and primary care, several challenges need to be considered and overcome, including 'buy in' from some GPs, branding, and funding for the third sector in a context where social care cuts are severely affecting the delivery of health care. With its emphasis on context and mechanisms, the realist evaluation approach is useful in understanding how to identify and improve health interventions, and analyse in greater detail the contribution of different stakeholders. As the SPC is central to social prescribing, more needs to be done to understand their role

  7. Primary physical mechanism of different magnetic fields action on roots of some plants

    Directory of Open Access Journals (Sweden)

    N. V. Sheykina

    2017-12-01

    Full Text Available Background: Though the magnetic field action on biological object is proved now by many experiments it cannot be explained. The counterarguments are the small value of magnetic induction, that is effective for static magnetic field and the small value of ions free path length for ion cyclotron resonance presence.   Objectives of the article were to generalize all the results that had been obtained before in static, alternative and combined magnetic fields and to explain all results by one and the same primary physical mechanism. Materials and methods that were used to obtain experimental results were based on the using of well reproducible magnetic conditions. For this purpose 3 lays µ-metal shield and superconductive shield with warm volume were used. The artificial magnetic field was created in the shield. The objects of the investigation were roots of cress, maize and pea. Their gravitropic reaction was studied. Results and discussion: All experimental results were compared with the theories and calculations maid before and following from the three mechanisms proposed below.  It was shown that there were three physical primary mechanisms that could lead to effect of low frequency alternative and combined magnetic fields and permanent magnetic field on gravitropic reaction in plants. All of them depended on the relative location of roots, gravity and components of permanent and alternative magnetic fields between themselves. The first mechanism is based on the classic model of the rotation of ions in the plane that is perpendicular to the magnetic field direction or precession of magnetic moments round the direction of magnetic field vector. The second mechanism is connected with the piezoelectric properties of starch grain (porous piezoelectricity. This property of starch may create the change in the moving of starch grains in alternative and combined magnetic fields, and even in static one. The third mechanism is caused by the phase

  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. 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...

  10. Comparative overview of primary sedimentation-based mechanical stage in some Romanian wastewater treatment systems

    Science.gov (United States)

    Zaharia, C.

    2017-08-01

    Nowadays, wastewater (WW) treatment facilities are considered significant exposure pathways for solid particles, and also significant concerns of any quality conscious manufacturer. Most solid particles have some forms of organic coating either used as active material or to suspend and/or stabilize different present solid materials, having increase in toxicity that must be reduced, or sometimes even totally eliminated, especially if effluent is either discharged directly to surface water, or distributed through industrial water supplies. Representatives providing innovative technologies, comprehensive supports and expertise in wastewater and sludge treatment field are known, each one using modern treatment technology and facilities. Mechanical treatment is indispensable in primary treatment steps of both municipal and industrial WW applications, its main goal being separation of floating, settling and suspended materials (especially into a primary sedimentation-based treatment step). The aim of this work is to present comparatively the performance in solids removal of conventional mechanical WW treatment stages, especially those based on primary sedimentation, or sedimentation-like operations applied for Romanian urban WW treatment plants (serving two towns with ca 18,000 inhabitants), industrial WW treatment plants (deserving industries of vegetal food processing and organic chemicals’ manufacturing) and additional information on valorisation of separated solid material and improvement possibilities.

  11. 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.

  12. Incidence of emergency contacts (red responses to Norwegian emergency primary healthcare services in 2007 – a prospective observational study

    Directory of Open Access Journals (Sweden)

    Hansen Elisabeth

    2009-07-01

    Full Text Available Abstract Background The municipalities are responsible for the emergency primary health care services in Norway. These services include casualty clinics, primary doctors on-call and local emergency medical communication centres (LEMC. The National centre for emergency primary health care has initiated an enterprise called "The Watchtowers", comprising emergency primary health care districts, to provide routine information (patients' way of contact, level of urgency and first action taken by the out-of-hours services over several years based on a minimal dataset. This will enable monitoring, evaluation and comparison of the respective activities in the emergency primary health care services. The aim of this study was to assess incidence of emergency contacts (potential life-threatening situations, red responses to the emergency primary health care service. Methods A representative sample of Norwegian emergency primary health care districts, "The Watchtowers" recorded all contacts and first action taken during the year of 2007. All the variables were continuously registered in a data program by the attending nurses and sent by email to the National Centre for Emergency Primary Health Care at a monthly basis. Results During 2007 the Watchtowers registered 85 288 contacts, of which 1 946 (2.3% were defined as emergency contacts (red responses, corresponding to a rate of 9 per 1 000 inhabitants per year. 65% of the instances were initiated by patient, next of kin or health personnel by calling local emergency medical communication centres or meeting directly at the casualty clinics. In 48% of the red responses, the first action taken was a call-out of doctor and ambulance. On a national basis we can estimate approximately 42 500 red responses per year in the EPH in Norway. Conclusion The emergency primary health care services constitute an important part of the emergency system in Norway. Patients call the LEMC or meet directly at casualty clinics

  13. Cytotoxic mechanisms of hydrosulfide anion and cyanide anion in primary rat hepatocyte cultures

    International Nuclear Information System (INIS)

    Thompson, Rodney W.; Valentine, Holly L.; Valentine, William M.

    2003-01-01

    Hydrogen sulfide and hydrogen cyanide are known to compromise mitochondrial respiration through inhibition of cytochrome c oxidase and this is generally considered to be their primary mechanism of toxicity. Experimental studies and the efficiency of current treatment protocols suggest that H 2 S may exert adverse physiological effects through additional mechanisms. To evaluate the role of alternative mechanisms in H 2 S toxicity, the relative contributions of electron transport inhibition, uncoupling of mitochondrial respiration, and opening of the mitochondrial permeability transition pore (MPTP) to hydrosulfide and cyanide anion cytotoxicity in primary hepatocyte cultures were examined. Supplementation of hepatocytes with the glycolytic substrate, fructose, rescued hepatocytes from cyanide anion induced toxicity, whereas fructose supplementation increased hydrosulfide anion toxicity suggesting that hydrosulfide anion may compromise glycolysis in hepatocytes. Although inhibitors of the MPTP opening were protective for hydrosulfide anion, they had no effect on cyanide anion toxicity, consistent with an involvement of the permeability transition pore in hydrosulfide anion toxicity but not cyanide anion toxicity. Exposure of isolated rat liver mitochondria to hydrosulfide did not result in large amplitude swelling suggesting that if H 2 S induces the permeability transition it does so indirectly through a mechanism requiring other cellular components. Hydrosulfide anion did not appear to be an uncoupler of mitochondrial respiration in hepatocytes based upon the inability of oligomycin and fructose to protect hepatocytes from hydrosulfide anion toxicity. These findings support mechanisms additional to inhibition of cytochrome c oxidase in hydrogen sulfide toxicity. Further investigations are required to assess the role of the permeability transition in H 2 S toxicity, determine whether similar affects occur in other cell types or in vivo and evaluate whether this may

  14. 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.

  15. 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

  16. 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

  17. Metabolic responses of primary and transformed cells to intracellular Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Nadine Gillmaier

    Full Text Available The metabolic response of host cells, in particular of primary mammalian cells, to bacterial infections is poorly understood. Here, we compare the carbon metabolism of primary mouse macrophages and of established J774A.1 cells upon Listeria monocytogenes infection using (13C-labelled glucose or glutamine as carbon tracers. The (13C-profiles of protein-derived amino acids from labelled host cells and intracellular L. monocytogenes identified active metabolic pathways in the different cell types. In the primary cells, infection with live L. monocytogenes increased glycolytic activity and enhanced flux of pyruvate into the TCA cycle via pyruvate dehydrogenase and pyruvate carboxylase, while in J774A.1 cells the already high glycolytic and glutaminolytic activities hardly changed upon infection. The carbon metabolism of intracellular L. monocytogenes was similar in both host cells. Taken together, the data suggest that efficient listerial replication in the cytosol of the host cells mainly depends on the glycolytic activity of the hosts.

  18. Mechanical Properties of Post Irradiation Primary Cooling Piping of Bandung Research Reactor

    International Nuclear Information System (INIS)

    Histori; Renaningsih S; Sri Nitiswati; Ari Triyadi

    2003-01-01

    Testing on primary coolant piping of research reactor Bandung have been done. Primary coolant piping were made from Al 6061-T6. The goal of this activity is to investigate the mechanical properties changes caused by aging process after 33 years in irradiated. Type of testing i.e visual examination, thickness measurement, tensile and hardness test were done. The test data shown that there was a deposit at the inside surface of pipe, thickness decreased about 0.2 mm, tensile strength is 293 MPa, yield strength is 262 MPa, while the hardness is about 83 HRE (mean value). The test data than compared with ASTM standard. As the conclusion tensile and yield strength of pipe still fulfill the ASTM requirements, except the hardness is unsignificantly less/decreased. (author)

  19. Adding Postal Follow-Up to a Web-Based Survey of Primary Care and Gastroenterology Clinic Physician Chiefs Improved Response Rates but not Response Quality or Representativeness.

    Science.gov (United States)

    Partin, Melissa R; Powell, Adam A; Burgess, Diana J; Haggstrom, David A; Gravely, Amy A; Halek, Krysten; Bangerter, Ann; Shaukat, Aasma; Nelson, David B

    2015-09-01

    This study assessed whether postal follow-up to a web-based physician survey improves response rates, response quality, and representativeness. We recruited primary care and gastroenterology chiefs at 125 Veterans Affairs medical facilities to complete a 10-min web-based survey on colorectal cancer screening and diagnostic practices in 2010. We compared response rates, response errors, and representativeness in the primary care and gastroenterology samples before and after adding postal follow-up. Adding postal follow-up increased response rates by 20-25 percentage points; markedly greater increases than predicted from a third e-mail reminder. In the gastroenterology sample, the mean number of response errors made by web responders (0.25) was significantly smaller than the mean number made by postal responders (2.18), and web responders provided significantly longer responses to open-ended questions. There were no significant differences in these outcomes in the primary care sample. Adequate representativeness was achieved before postal follow-up in both samples, as indicated by the lack of significant differences between web responders and the recruitment population on facility characteristics. We conclude adding postal follow-up to this web-based physician leader survey improved response rates but not response quality or representativeness. © The Author(s) 2013.

  20. Stressors and Stressor Response Levels of Hong Kong Primary School Music Teachers

    Science.gov (United States)

    Wong, Marina Wai-yee; Chik, Maria Pik-yuk; Chan, Edmund Sze Shing

    2018-01-01

    Responses from 309 randomly sampled Hong Kong primary school music teachers to the shortened version of the Chinese Teacher Stress Questionnaire were subjected to a descriptive percentage analysis, one-way ANOVA and independent t test. Obtained results identify five key stressors: "changing education policy of the government";…

  1. Obesity in primary care: a qualitative synthesis of patient and practitioner perspectives on roles and responsibilities.

    Science.gov (United States)

    Henderson, Emily

    2015-04-01

    Obesity is a top-priority global health issue; however, a clear way to address obesity in primary care is not yet in view. To conduct a meta-ethnography of patient and primary care practitioner perspectives of roles and responsibilities in how to address obesity in the UK, to inform evidence-based services that are acceptable to, and appropriate for, patients and practitioners. Qualitative synthesis applying meta-ethnographic methods according to the Noblit and Hare monograph. Database searches in MEDLINE(®), Social Sciences Citation Index(®), CINAHL, and Health Management Information Consortium were limited to 1997-2012 to examine recent perspectives. Full articles of practitioner and/or patient perspectives on obesity services in primary care were reviewed, and included semi-structured or unstructured interviews and focus groups, and participant observations. Nine studies were synthesised with perspectives from patients (n = 105) and practitioners (n = 144). Practitioners believe that patients are responsible for obesity, and that primary care should not help, or is poorly equipped to do so. Patients 'take responsibility' by 'blaming' themselves, but feel that practitioners should demonstrate more leadership. The empowerment of patients to access health services is reliant on the empowerment of practitioners to take an unambiguous position. Primary care has the potential either to perpetuate or counter obesity-related stigma. There needs to be a firm decision as to what role primary care will take in the prevention and treatment of obesity. To remain ambiguous runs the risk of losing patients' confidence and adding to a growing sense of futility. © British Journal of General Practice 2015.

  2. 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.

  3. The short-term stress response - Mother nature's mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity.

    Science.gov (United States)

    Dhabhar, Firdaus S

    2018-03-26

    Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Effects of segregation of primary alloying elements on the creep response in magnesium alloys

    DEFF Research Database (Denmark)

    Huang, Y.D.; Dieringa, H.; Hort, N.

    2008-01-01

    The segregation of primary alloying elements deteriorates the high temperature creep resistance of magnesium alloys. Annealing at high temperatures alleviating their segregations can improve the creep resistance. Present investigation on the effect of segregation of primary alloying elements...... on the creep response may provide some useful information about how to improve the creep resistance of magnesium alloys in the future. (c) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved....

  5. 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...

  6. 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.

  7. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

    Directory of Open Access Journals (Sweden)

    Elise Landais

    2016-01-01

    Full Text Available Broadly neutralizing antibodies (bnAbs are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(- genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

  8. 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....

  9. 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

  10. Association between gene expression profile of the primary tumor and chemotherapy response of metastatic breast cancer

    NARCIS (Netherlands)

    Savci-Heijink, Cemile Dilara; Halfwerk, Hans; Koster, Jan; van de Vijver, Marc Joan

    2017-01-01

    Background: To better predict the likelihood of response to chemotherapy, we have conducted a study comparing the gene expression patterns of primary tumours with their corresponding response to systemic chemotherapy in the metastatic setting. Methods: mRNA expression profiles of breast carcinomas

  11. Mechanical and corrosion properties of Ni-Cr-Fe Alloy 600 related to primary side SCC

    International Nuclear Information System (INIS)

    Begley, J.A.; Jacko, R.J.; Gold, R.E.

    1987-01-01

    The two-fold objective of the program is to provide the mechanical property data required for the development of a strain rate damage model for environmentally assisted cracking of Inconel 600 and to evaluate critical damage model parameters in primary water environments by conducting a series of stress corrosion tests. The test program includes mechanical property tests at 20 0 C, 316 0 C and strain rate tests to determine critical strain rate SCC parameters in primary water environments. Data are presented from slow strain rate tensile tests, stress relaxation tests and creep tests. A short discussion of the Gerber-Garud Strain Rate Damage Model is included to provide the background rationale for the test program. Utilitarian aspects of the Strain Rate Damage Model and the test program data are presented. Analysis of accelerated stress corrosion testing at high temperatures, and the contribution of thermally activated inelastic deformation to apparent activation energies for stress corrosion cracking is emphasized

  12. 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.

  13. Asymmetric Responses of Primary Productivity to Altered Precipitation Simulated by Land Surface Models across Three Long-term Grassland Sites

    Science.gov (United States)

    Wu, D.; Ciais, P.; Viovy, N.; Knapp, A.; Wilcox, K.; Bahn, M.; Smith, M. D.; Ito, A.; Arneth, A.; Harper, A. B.; Ukkola, A.; Paschalis, A.; Poulter, B.; Peng, C.; Reick, C. H.; Hayes, D. J.; Ricciuto, D. M.; Reinthaler, D.; Chen, G.; Tian, H.; Helene, G.; Zscheischler, J.; Mao, J.; Ingrisch, J.; Nabel, J.; Pongratz, J.; Boysen, L.; Kautz, M.; Schmitt, M.; Krohn, M.; Zeng, N.; Meir, P.; Zhang, Q.; Zhu, Q.; Hasibeder, R.; Vicca, S.; Sippel, S.; Dangal, S. R. S.; Fatichi, S.; Sitch, S.; Shi, X.; Wang, Y.; Luo, Y.; Liu, Y.; Piao, S.

    2017-12-01

    Changes in precipitation variability including the occurrence of extreme events strongly influence plant growth in grasslands. Field measurements of aboveground net primary production (ANPP) in temperate grasslands suggest a positive asymmetric response with wet years resulting in ANPP gains larger than ANPP declines in dry years. Whether land surface models used for historical simulations and future projections of the coupled carbon-water system in grasslands are capable to simulate such non-symmetrical ANPP responses remains an important open research question. In this study, we evaluate the simulated responses of grassland primary productivity to altered precipitation with fourteen land surface models at the three sites of Colorado Shortgrass Steppe (SGS), Konza prairie (KNZ) and Stubai Valley meadow (STU) along a rainfall gradient from dry to wet. Our results suggest that: (i) Gross primary production (GPP), NPP, ANPP and belowground NPP (BNPP) show nonlinear response curves (concave-down) in all the models, but with different curvatures and mean values. In contrast across the sites, primary production increases and then saturates along increasing precipitation with a flattening at the wetter site. (ii) Slopes of spatial relationships between modeled primary production and precipitation are steeper than the temporal slopes (obtained from inter-annual variations). (iii) Asymmetric responses under nominal precipitation range with modeled inter-annual primary production show large uncertainties, and model-ensemble median generally suggests negative asymmetry (greater declines in dry years than increases in wet years) across the three sites. (iv) Primary production at the drier site is predicted to more sensitive to precipitation compared to wetter site, and median sensitivity consistently indicates greater negative impacts of reduced precipitation than positive effects of increased precipitation under extreme conditions. This study implies that most models

  14. 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.

  15. 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.

  16. Modulation of Neuronal Responses by Exogenous Attention in Macaque Primary Visual Cortex.

    Science.gov (United States)

    Wang, Feng; Chen, Minggui; Yan, Yin; Zhaoping, Li; Li, Wu

    2015-09-30

    Visual perception is influenced by attention deployed voluntarily or triggered involuntarily by salient stimuli. Modulation of visual cortical processing by voluntary or endogenous attention has been extensively studied, but much less is known about how involuntary or exogenous attention affects responses of visual cortical neurons. Using implanted microelectrode arrays, we examined the effects of exogenous attention on neuronal responses in the primary visual cortex (V1) of awake monkeys. A bright annular cue was flashed either around the receptive fields of recorded neurons or in the opposite visual field to capture attention. A subsequent grating stimulus probed the cue-induced effects. In a fixation task, when the cue-to-probe stimulus onset asynchrony (SOA) was visual fields weakened or diminished both the physiological and behavioral cueing effects. Our findings indicate that exogenous attention significantly modulates V1 responses and that the modulation strength depends on both novelty and task relevance of the stimulus. Significance statement: Visual attention can be involuntarily captured by a sudden appearance of a conspicuous object, allowing rapid reactions to unexpected events of significance. The current study discovered a correlate of this effect in monkey primary visual cortex. An abrupt, salient, flash enhanced neuronal responses, and shortened the animal's reaction time, to a subsequent visual probe stimulus at the same location. However, the enhancement of the neural responses diminished after repeated exposures to this flash if the animal was not required to react to the probe. Moreover, a second, simultaneous, flash at another location weakened the neuronal and behavioral effects of the first one. These findings revealed, beyond the observations reported so far, the effects of exogenous attention in the brain. Copyright © 2015 the authors 0270-6474/15/3513419-11$15.00/0.

  17. 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.

  18. The impact of human immunodeficiency virus (HIV) service scale-up on mechanisms of accountability in Zambian primary health centres: a case-based health systems analysis.

    Science.gov (United States)

    Topp, Stephanie M; Black, Jim; Morrow, Martha; Chipukuma, Julien M; Van Damme, Wim

    2015-02-18

    Questions about the impact of large donor-funded HIV interventions on low- and middle-income countries' health systems have been the subject of a number of expert commentaries, but comparatively few empirical research studies. Aimed at addressing a particular evidence gap vis-à-vis the influence of HIV service scale-up on micro-level health systems, this article examines the impact of HIV scale-up on mechanisms of accountability in Zambian primary health facilities. Guided by the Mechanisms of Effect framework and Brinkerhoff's work on accountability, we conducted an in-depth multi-case study to examine how HIV services influenced mechanisms of administrative and social accountability in four Zambian primary health centres. Sites were selected for established (over 3 yrs) antiretroviral therapy (ART) services and urban, peri-urban and rural characteristics. Case data included provider interviews (60); patient interviews (180); direct observation of facility operations (2 wks/centre) and key informant interviews (14). Resource-intensive investment in HIV services contributed to some early gains in administrative answerability within the four ART departments, helping to establish the material capabilities necessary to deliver and monitor service delivery. Simultaneous investment in external supervision and professional development helped to promote transparency around individual and team performance and also strengthened positive work norms in the ART departments. In the wider health centres, however, mechanisms of administrative accountability remained weak, hindered by poor data collection and under capacitated leadership. Substantive gains in social accountability were also elusive as HIV scale-up did little to address deeply rooted information and power asymmetries in the wider facilities. Short terms gains in primary-level service accountability may arise from investment in health system hardware. However, sustained improvements in service quality and

  19. Conceptual design and related R and D on ITER mechanical based primary pumping system

    International Nuclear Information System (INIS)

    Tanzawa, Sadamitsu; Hiroki, Seiji; Abe, Tetsuya; Shimizu, Katsusuke; Inoue, Masahiko; Watanabe, Mitsunori; Iguchi, Masashi; Sugimoto, Tomoko; Inohara, Takashi; Nakamura, Jun-ichi

    2008-12-01

    The primary vacuum pumping system of the International Thermonuclear Experimental Reactor (ITER) exhausts a helium (He) ash resulting from the DT-burn with excess DT fueling gas, as well as performing a variety of functions such as pump-down, leak testing and wall conditioning. A mechanical based vacuum pumping system has some merits of a continuous pumping, a much lower tritium inventory, a lower operational cost and easy maintenance, comparing with a cryopump system, although demerits of an indispensable magnetic shield and insufficient performance for hydrogen (H 2 ) pumping is are well recognized. To overcome the demerits, we newly fabricated and tested a helical grooved pump (HGP) unit suitable for H 2 pumping at the ITER divertor pressure of 0.1-10 Pa. Through this R and D, we successfully established many design and manufacturing databases of large HGP units for the lightweight gas pumping. Based on the databases, we conceptually designed the ITER vacuum pumping system mainly comprising the HGP with an optimal pump unit layout and a magnetic shield. We also designed conceptually the reduced cost (RC)-ITER pumping system, where a compound molecular pump combining turbine bladed rotors and helical grooved ones was mainly used. The ITER mechanical based primary pumping system proposed has eventually been a back-up solution, whereas a cryopump based one was formally selected to the ITER for construction. The mechanical pumps are increasingly used in many areas with well sophisticated performance, so we believe that fusion reactors of subsequent prototype ones will select the mechanical based pumping system due to primarily a high operational reliability and a cost melt. (author)

  20. 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.

  1. 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.

  2. Mechanical disruption of tumors by iron particles and magnetic field application results in increased anti-tumor immune responses.

    Directory of Open Access Journals (Sweden)

    Myriam N Bouchlaka

    Full Text Available The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread. This treatment was associated with increased activation of DCs in the draining lymph nodes and recruitment of both DCs and CD8(+T cells to the tumor. The particles remained within the tumor and no toxicities were observed. The immune induction observed was significantly greater compared to cryoablation. Further anti-tumor effects were observed when MRF/magnet therapy was combined with systemic low dose immunotherapy. Thus, mechanical disruption of the primary tumor with MRF/magnetic field application represents a novel means to induce systemic immune activation in cancer.

  3. Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis

    DEFF Research Database (Denmark)

    Hvass, Henriette Cordes; Riber, Ulla; Jensen, Tim Kåre

    2012-01-01

    not boosted by the re-inoculation, since identical intestinal IgA responses developed in response to the inoculation in both the susceptible CC pigs and the protected RE pigs. A memory recall cell-mediated immune response developed in RE pigs which was significantly stronger compared to the primary response...... responses are likely mediators of protective immunity against L. intracellularis, with CD8+ effector cells and CD4+CD8+ double positive memory T cells as main contributors to the antigen-specific IFN-γ production....

  4. Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity

    NARCIS (Netherlands)

    Hof, W.F.P.M.; Summeren, van A.; Lommen, A.; Coonen, M.L.J.; Brauers, K.; Herwijnen, van M.; Wodzig, W.K.W.H.; Kleinjans, J.C.S.

    2014-01-01

    The liver is responsible for drug metabolism and drug-induced hepatotoxicity is the most frequent reason for drug withdrawal, indicating that better pre-clinical toxicity tests are needed. In order to bypass animal models for toxicity screening, we exposed primary mouse hepatocytes for exploring the

  5. Mechanisms of acetaminophen-induced cell death in primary human hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yuchao; McGill, Mitchell R.; Dorko, Kenneth [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2014-09-15

    Acetaminophen (APAP) overdose is the most prevalent cause of drug-induced liver injury in western countries. Numerous studies have been conducted to investigate the mechanisms of injury after APAP overdose in various animal models; however, the importance of these mechanisms for humans remains unclear. Here we investigated APAP hepatotoxicity using freshly isolated primary human hepatocytes (PHH) from either donor livers or liver resections. PHH were exposed to 5 mM, 10 mM or 20 mM APAP over a period of 48 h and multiple parameters were assessed. APAP dose-dependently induced significant hepatocyte necrosis starting from 24 h, which correlated with the clinical onset of human liver injury after APAP overdose. Interestingly, cellular glutathione was depleted rapidly during the first 3 h. APAP also resulted in early formation of APAP-protein adducts (measured in whole cell lysate and in mitochondria) and mitochondrial dysfunction, indicated by the loss of mitochondrial membrane potential after 12 h. Furthermore, APAP time-dependently triggered c-Jun N-terminal kinase (JNK) activation in the cytosol and translocation of phospho-JNK to the mitochondria. Both co-treatment and post-treatment (3 h) with the JNK inhibitor SP600125 reduced JNK activation and significantly attenuated cell death at 24 h and 48 h after APAP. The clinical antidote N-acetylcysteine offered almost complete protection even if administered 6 h after APAP and a partial protection when given at 15 h. Conclusion: These data highlight important mechanistic events in APAP toxicity in PHH and indicate a critical role of JNK in the progression of injury after APAP in humans. The JNK pathway may represent a therapeutic target in the clinic. - Highlights: • APAP reproducibly causes cell death in freshly isolated primary human hepatocytes. • APAP induces adduct formation, JNK activation and mitochondrial dysfunction in PHH. • Mitochondrial adducts and JNK translocation are delayed in PHH compared to

  6. Primary blast-induced traumatic brain injury: lessons from lithotripsy

    Science.gov (United States)

    Nakagawa, A.; Ohtani, K.; Armonda, R.; Tomita, H.; Sakuma, A.; Mugikura, S.; Takayama, K.; Kushimoto, S.; Tominaga, T.

    2017-11-01

    Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics

  7. 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

  8. 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...

  9. 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.

  10. 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

  11. Extraction mechanism of Sc(III) from sulphuric acid solution by primary amine N1923

    International Nuclear Information System (INIS)

    Le Shaoming; Li Deqian; Ni Jiazan

    1987-01-01

    The extraction mechanism of Sc(III) from sulphuric acid solution by primary amine N 1923 (RNH 2 ) has been investigated by means of slope, isomolar continuous variation and saturation methods. The effect of temperature on the extraction of Sc(III) is observed. The extraction equilibrium constant and thermodynamic functions (ΔH, ΔS and ΔG) are obtained. The IR and NMR of extracted compound are measured

  12. 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)

  13. Modeling of primary water stress corrosion cracking at control rod drive mechanism nozzles of pressurized water reactors

    International Nuclear Information System (INIS)

    Aly, Omar Fernandes

    2006-01-01

    One of the main failure mechanisms that cause risks to pressurized water reactors is the primary water stress corrosion cracking (PWSCC) occurring in alloys. It can occurs, besides another places, at the control reactor displacement mechanism nozzles. It is caused by the joint effect of tensile stress, temperature, susceptible metallurgical microstructure and environmental conditions of the primary water. These cracks can cause accidents that reduce nuclear safety by blocking the rod's displacement and may cause leakage of primary water, reducing the reactor's life. In this work it is proposed a study of the existing models and a modeling proposal to primary water stress corrosion cracking in these nozzles in a nickel based Alloy 600. It is been superposed electrochemical and fracture mechanics models, and validated using experimental and literature data. The experimental data were obtained at CDTN-Brazilian Nuclear Technology Development Center, in a recent installed slow strain rate testing equipment. In the literature it is found a diagram that indicates a thermodynamic condition for the occurrence of some PWSCC sub modes in Alloy 600: it was used potential x pH diagrams (Pourbaix diagrams), for Alloy 600 in high temperature primary water (300 deg C till 350 deg C). Over it, were located the PWSCC sub modes, using experimental data. It was added a third parameter called 'stress corrosion strength fraction'. However, it is possible to superpose to this diagram, other parameters expressing PWSCC initiation or growth kinetics from other models. Here is the proposition of the original contribution of this work: from an original experimental condition of potential versus pH, it was superposed, an empiric-comparative, a semi-empiric-probabilistic, an initiation time, and a strain rate damage models, to quantify respectively the PWSCC susceptibility, the failure time, and in the two lasts, the initiation time of stress corrosion cracking. It was modeling from our

  14. Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?

    Directory of Open Access Journals (Sweden)

    Marwa Elamin

    2017-11-01

    Full Text Available The ketogenic diet’s (KD anticonvulsant effects have been well-documented for nearly a century, including in randomized controlled trials. Some patients become seizure-free and some remain so after diet cessation. Many recent studies have explored its expanded therapeutic potential in diverse neurological disorders, yet no mechanism(s of action have been established. The diet’s high fat, low carbohydrate composition reduces glucose utilization and promotes the production of ketone bodies. Ketone bodies are a more efficient energy source than glucose and improve mitochondrial function and biogenesis. Cellular energy production depends on the metabolic coenzyme nicotinamide adenine dinucleotide (NAD, a marker for mitochondrial and cellular health. Furthermore, NAD activates downstream signaling pathways (such as the sirtuin enzymes associated with major benefits such as longevity and reduced inflammation; thus, increasing NAD is a coveted therapeutic endpoint. Based on differential NAD+ utilization during glucose- vs. ketone body-based acetyl-CoA generation for entry into the tricarboxylic cycle, we propose that a KD will increase the NAD+/NADH ratio. When rats were fed ad libitum KD, significant increases in hippocampal NAD+/NADH ratio and blood ketone bodies were detected already at 2 days and remained elevated at 3 weeks, indicating an early and persistent metabolic shift. Based on diverse published literature and these initial data we suggest that increased NAD during ketolytic metabolism may be a primary mechanism behind the beneficial effects of this metabolic therapy in a variety of brain disorders and in promoting health and longevity.

  15. Parameters affecting mechanical and thermal responses in bone drilling: A review.

    Science.gov (United States)

    Lee, JuEun; Chavez, Craig L; Park, Joorok

    2018-04-11

    Surgical bone drilling is performed variously to correct bone fractures, install prosthetics, or for therapeutic treatment. The primary concern in bone drilling is to extract donor bone sections and create receiving holes without damaging the bone tissue either mechanically or thermally. We review current results from experimental and theoretical studies to investigate the parameters related to such effects. This leads to a comprehensive understanding of the mechanical and thermal aspects of bone drilling to reduce their unwanted complications. This review examines the important bone-drilling parameters of bone structure, drill-bit geometry, operating conditions, and material evacuation, and considers the current techniques used in bone drilling. We then analyze the associated mechanical and thermal effects and their contributions to bone-drilling performance. In this review, we identify a favorable range for each parameter to reduce unwanted complications due to mechanical or thermal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Participation and factors associated with late or non-response to an online survey in primary care.

    Science.gov (United States)

    Aerny-Perreten, Nicole; Domínguez-Berjón, Ma Felicitas; Esteban-Vasallo, María D; García-Riolobos, Carmen

    2015-08-01

    Online surveys have several advantages, but a low response rate is common and it is uncertain how results are affected. Response inducement techniques can be used to overcome this problem. The objectives of this study were to describe the percentage of change in the response rate after reminders and to analyse the characteristics associated with non-response and late response based on the survey results, as well as by applying archival and extrapolation techniques. In the Autonomous Community of Madrid, an online questionnaire about cancer prevention was sent to a random sample of primary care health professionals (3586 physicians and nurses). Two reminders were sent later. The percentage of change in response rates after reminders, global and by demographic and health care characteristics of participants; and factors associated with non-response and late response were analysed using response rates and odds ratios (ORs). After the reminders, the response rate increased from 22.6% to 32.9% and to 39.4%. Non-response was associated with age [OR: 3.14; confidence interval (CI) 95%: 2.23-4.42 for aged >60 years], gender and functional area. Further, a higher response rate after reminders was observed in professionals with heavier workloads (OR: 1.46; CI 95%: 1.08-1.97) and in those who stated a lower relevance of cancer prevention in primary care. After electronic reminders, the response rate increased, especially among professionals with the highest workloads and a minor interest in the survey topic. However, possible bias associated with non-response remains and the factors behind this should be examined in future research. © 2015 John Wiley & Sons, Ltd.

  18. 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.

  19. A Case Study on Primary, Secondary and University Students' Environmentally Responsible Behaviors in Turkey

    Science.gov (United States)

    Kahyaoglu, Mustafa

    2013-01-01

    The purpose of the study is to prove the environmentally responsible behaviors of primary, secondary and university students in Turkey. The students', who attended the study as participants, environmentally political behaviors, consumer/economical behaviors, direct behaviors toward protecting the environment and individual and public persuasion…

  20. Investigating Nigerian Primary School Teachers' Preparedness to Adopt Personal Response System in ESL Classroom

    Science.gov (United States)

    Agbatogun, Alaba Olaoluwakotansibe

    2012-01-01

    This study investigated the extent to which computer literacy dimensions (computer general knowledge, documents and documentations, communication and surfing as well as data inquiry), computer use and academic qualification as independent variables predicted primary school teachers' attitude towards the integration of Personal Response System in…

  1. 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.

  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 Listeria monocytogenes cells on the primary immunologic response in irradiated mice

    International Nuclear Information System (INIS)

    Borowski, J.; Jokoniuk, P.

    1977-01-01

    The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

  4. 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

  5. Primary health care attributes and responses to intimate partner violence in Spain.

    Science.gov (United States)

    Goicolea, Isabel; Mosquera, Paola; Briones-Vozmediano, Erica; Otero-García, Laura; García-Quinto, Marta; Vives-Cases, Carmen

    This study provides an overview of the perceptions of primary care professionals on how the current primary health care (PHC) attributes in Spain could influence health-related responses to intimate partner violence (IPV). A qualitative study was conducted using semi-structured interviews with 160 health professionals working in 16 PHC centres in Spain. Data were analysed using a qualitative content analysis. Four categories emerged from the interview analysis: those committed to the PHC approach, but with difficulties implementing it; community work relying on voluntarism; multidisciplinary team work or professionals who work together?; and continuity of care hindered by heavy work load. Participants felt that person-centred care as well as other attributes of the PHC approach facilitated detecting IPV and a better response to the problem. However, they also pointed out that the current management of the health system (workload, weak supervision and little feedback, misdistribution of human and material resources, etc.) does not facilitate the sustainability of such an approach. There is a gap between the theoretical attributes of PHC and the "reality" of how these attributes are managed in everyday work, and how this influences IPV care. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. 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.

  7. 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.

  8. A microculture method for the generation of primary immune responses in vitro.

    Science.gov (United States)

    Pike, B L

    1975-11-01

    A microculture method for the generation and study of the primary immune response of murine spleen cells to defined antigens in vitro is described. Many of the variable parameters which occur in culture systems have been studied in an attempt to define the optimal culture conditions for this system. Cultures of 10(6) CBA spleen cells consistently produced an immune response of 300-600 hapten-specific plaque-forming cells after 3 days of incubation with the T cell-independent antigens DNP-POL and NIP-POL. Cultures were set up in Microtest II tissue culture plates in a volume of 0.2 ml of medium containing 10(-4) M 2-mercaptoethanol. The system described has the advantages of being highly efficient and reproducible and utilises small amounts of cells, medium and antigen. It provides a simple, economic and reliable approach for the systematic study of the immune response in vitro.

  9. 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.

  10. Cobalt-alloy implant debris induce HIF-1α hypoxia associated responses: a mechanism for metal-specific orthopedic implant failure.

    Directory of Open Access Journals (Sweden)

    Lauryn Samelko

    Full Text Available The historical success of orthopedic implants has been recently tempered by unexpected pathologies and early failures of some types of Cobalt-Chromium-Molybdenum alloy containing artificial hip implants. Hypoxia-associated responses to Cobalt-alloy metal debris were suspected as mediating this untoward reactivity at least in part. Hypoxia Inducible Factor-1α is a major transcription factor involved in hypoxia, and is a potent coping mechanism for cells to rapidly respond to changing metabolic demands. We measured signature hypoxia associated responses (i.e. HIF-1α, VEGF and TNF-α to Cobalt-alloy implant debris both in vitro (using a human THP-1 macrophage cell line and primary human monocytes/macrophages and in vivo. HIF-1α in peri-implant tissues of failed metal-on-metal implants were compared to similar tissues from people with metal-on-polymer hip arthroplasties, immunohistochemically. Increasing concentrations of cobalt ions significantly up-regulated HIF-1α with a maximal response at 0.3 mM. Cobalt-alloy particles (1 um-diameter, 10 particles/cell induced significantly elevated HIF-1α, VEGF, TNF-α and ROS expression in human primary macrophages whereas Titanium-alloy particles did not. Elevated expression of HIF-1α was found in peri-implant tissues and synovial fluid of people with failing Metal-on-Metal hips (n = 5 compared to failed Metal-on-Polymer articulating hip arthroplasties (n = 10. This evidence suggests that Cobalt-alloy, more than other metal implant debris (e.g. Titanium alloy, can elicit hypoxia-like responses that if unchecked can lead to unusual peri-implant pathologies, such as lymphocyte infiltration, necrosis and excessive fibrous tissue growths.

  11. Role of Wind Power in Primary Frequency Response of an Interconnection: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y. C.; Gevorgian, V.; Ela, E.; Singhvi, V.; Pourbeik, P.

    2013-09-01

    The electrical frequency of an interconnection must be maintained very close to its nominal level at all times. Large frequency deviations can lead to unintended consequences such as load shedding, instability, and machine damage, among others. Turbine governors of conventional generating units provide primary frequency response (PFR) to ensure that frequency deviations are not significant duringlarge transient events. Increasing penetrations of variable renewable generation, such as wind and solar power, and planned retirements of conventional thermal plants - and thus a reduction in the amount of suppliers with PFR capabilities - causes concerns about a decline of PFR and system inertia in North America. The capability of inverter-coupled wind generation technologies to contribute toPFR and inertia, if appropriately equipped with the necessary control features, can help alleviate concerns. However, these responses differ from those supplied by conventional generation and inertia, and it is not entirely understood how variable renewable generation will affect the system response at different penetration levels. This paper evaluates the impact of wind generation providing PFRand synthetic inertial response on a large interconnection.

  12. 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.

  13. Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue.

    Science.gov (United States)

    Mina, Lida; Soule, Sharon E; Badve, Sunil; Baehner, Fredrick L; Baker, Joffre; Cronin, Maureen; Watson, Drew; Liu, Mei-Lan; Sledge, George W; Shak, Steve; Miller, Kathy D

    2007-06-01

    Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

  14. A Novel Axial Foldable Mechanism for a Segmented Primary Mirror of Space Telescope

    Directory of Open Access Journals (Sweden)

    Dignesh Thesiya

    2015-09-01

    Full Text Available Future space missions will have larger telescopes in order to look deeper into space while improvising on spatial resolution. The primary mirrors for these telescopes will be so large that using a monolithic mirror will be nearly impossible because of the difficulties associated with its fabrication, transportation, and installation on a launch vehicle. The feasibility of launching these huge mirrors is limited because of their small launch fairing diameter. The aerodynamic shape of the fairing requires a small diameter, but the height of the launch vehicle, which is available for designers to utilize, is larger than the fairing diameter. This paper presents the development of an axial deployment mechanism based on the screw jack principle. The mechanism was designed and developed, and a prototype was constructed in order to demonstrate a lab model.

  15. 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....

  16. Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

    Science.gov (United States)

    Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

    1998-01-01

    The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

  17. RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy.

    Science.gov (United States)

    Pritzker, Kenneth; Pritzker, Laura; Generali, Daniele; Bottini, Alberto; Cappelletti, Maria Rosa; Guo, Baoqing; Parissenti, Amadeo; Trudeau, Maureen

    2015-05-01

    As there is now evidence that switching clinical nonresponders early in primary systemic therapy to alternate treatment regimens can enhance survival in some breast cancer patients, the need for a robust intermediate endpoint that can guide treatment response across all tumor subtypes is urgent. Recently, chemotherapy drugs have been shown to induce a decrease in RNA quality in tumor cells from breast cancer biopsies in some patients at midtherapy, and that this has been associated with subsequent achievement of pathological complete response (pCR). The decrease in RNA quality has been shown to be associated with RNA disruption; aberrant RNA bands visualized by RNA electrophoresis have been associated with subsequent tumor cell death. The objectives of these studies are to show that a new assay based on induction of RNA disruption in tumor cells by chemotherapy can stratify at midtherapy, pCR responders from non-pCR responders irrespective of clinical response and to present early evidence that clinically useful RNA disruption can be detected as early as 14 days after initiation of treatment. RNA disruption in tumor cells was quantified by analysis of the RNA electrophoresis banding pattern and expressed as an RNA disruption index (RDI). To develop the RNA disruption assay (RDA), RDI was correlated with clinical outcome (pCR) from the NCIC-CTG MA.22 breast cancer clinical trial (ClinicalTrials.gov NCT00066443). RDA Zones were established by stratifying patients using RDI values into Zone 1, Zone 2, and Zone 3. Zone 3 included seven out of eight pCR responders, whereas Zone 1 contained no pCR responders. An intermediate zone (Zone 2) was established which contained one pCR. Subsequently, to determine early drug response, RNA disruption was examined by RDI after 14 days exposure to trastuzumab, zoledronic acid, or letrozole + cyclophosphamide ± sorafenib therapy. In MA.22, RDA stratified 23 of 85 patients in Zone 1 as pCR nonresponders, 24 patients in Zone 2, an

  18. How the concept of biochemical response influenced the management of primary biliary cholangitis over time

    NARCIS (Netherlands)

    Lammers, W. J.; Leeman, M.; Ponsioen, C. I. J.; Boonstra, K.; van Erpecum, K. J.; Wolfhagen, F. H. J.; Kuyvenhoven, J. Ph; Vrolijk, J. M.; Drenth, J. P. H.; Witteman, E. M.; van Nieuwkerk, C. M. J.; van der Spek, B. W.; Witteman, B. J. M.; Erkelens, G. W.; Verhagen, M. A. M. T.; van Tuyl, S. A. C.; Poen, A. C.; Brouwer, J. T.; ter Borg, F.; Koek, G. H.; van Ditzhuijsen, T. J. M.; Hansen, B. E.; van Buuren, H. R.

    2016-01-01

    Criteria assessing biochemical response to ursodeoxycholic acid (UDCA) are established risk stratification tools in primary biliary cholangitis (PBC). We aimed to evaluate to what extent liver tests influenced patient management during a three decade period, and whether this changed over time. 851

  19. 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.

  20. 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

  1. CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

    International Nuclear Information System (INIS)

    Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young

    2011-01-01

    Highlights: → Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. → JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. → Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. → CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.

  2. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid.

    Science.gov (United States)

    Hirschfield, Gideon M; Mason, Andrew; Luketic, Velimir; Lindor, Keith; Gordon, Stuart C; Mayo, Marlyn; Kowdley, Kris V; Vincent, Catherine; Bodhenheimer, Henry C; Parés, Albert; Trauner, Michael; Marschall, Hanns-Ulrich; Adorini, Luciano; Sciacca, Cathi; Beecher-Jones, Tessa; Castelloe, Erin; Böhm, Olaf; Shapiro, David

    2015-04-01

    We evaluated the efficacy and safety of obeticholic acid (OCA, α-ethylchenodeoxycholic acid) in a randomized controlled trial of patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid therapy. We performed a double-blind study of 165 patients with primary biliary cirrhosis (95% women) and levels of alkaline phosphatase (ALP) 1.5- to 10-fold the upper limit of normal. Patients were randomly assigned to groups given 10 mg, 25 mg, or 50 mg doses of OCA or placebo, once daily for 3 months. Patients maintained their existing dose of ursodeoxycholic acid throughout the study. The primary outcome was change in level of ALP from baseline (day 0) until the end of the study (day 85 or early termination). We also performed an open-label extension of the trial in which 78 patients were enrolled and 61 completed the first year. OCA was superior to placebo in achieving the primary end point. Subjects given OCA had statistically significant relative reductions in mean ALP from baseline to the end of the study (P ursodeoxycholic acid. The incidence and severity of pruritus were lowest among patients who received 10 mg/d OCA. Biochemical responses to OCA were maintained in a 12-month open-label extension trial. ClinicalTrials.gov ID: NCT00550862. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  3. Advancing general practice nursing in Australia: roles and responsibilities of primary healthcare organisations.

    Science.gov (United States)

    Lane, Riki; Halcomb, Elizabeth; McKenna, Lisa; Zwar, Nicholas; Naccarella, Lucio; Davies, Gawaine Powell; Russell, Grant

    2017-05-01

    Objectives Given increased numbers and enhanced responsibilities of Australian general practice nurses, we aimed to delineate appropriate roles for primary health care organisations (PHCOs) to support this workforce. Methods A two-round online Delphi consensus process was undertaken between January and June 2012, informed by literature review and key informant interviews. Participants were purposively selected and included decision makers from government and professional organisations, educators, researchers and clinicians from five Australian states and territories Results Of 56 invited respondents, 35 (62%) and 31 (55%) responded to the first and second invitation respectively. Participants reached consensus on five key roles for PHCOs in optimising nursing in general practice: (1) matching workforce size and skills to population needs; (2) facilitating leadership opportunities; (3) providing education and educational access; (4) facilitating integration of general practice with other primary care services to support interdisciplinary care; and (5) promoting advanced nursing roles. National concerns, such as limited opportunities for postgraduate education and career progression, were deemed best addressed by national nursing organisations, universities and peak bodies. Conclusions Advancement of nursing in general practice requires system-level support from a range of organisations. PHCOs play a significant role in education and leadership development for nurses and linking national nursing organisations with general practices. What is known about the topic? The role of nurses in Australian general practice has grown in the last decade, yet they face limited career pathways and opportunities for career advancement. Some nations have forged interprofessional primary care teams that use nurses' skills to the full extent of their scope of practice. PHCOs have played important roles in the development of general practice nursing in Australia and internationally

  4. 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.

  5. 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

  6. Quasi-static and dynamic compressive deformation of a bulk nanolayered Ag–Cu eutectic alloy: Macroscopic response and dominant deformation mechanisms

    International Nuclear Information System (INIS)

    Kingstedt, O.T.; Eftink, B.; Lambros, J.; Robertson, I.M.

    2014-01-01

    Nanostructured multilayered material systems offer an attractive method of increasing material strength. This work examines the response of a bulk eutectic silver–copper material (Ag 60 Cu 40 , subscripts indicating atomic percent) which has a hierarchical structure of alternating Ag and Cu layers with thicknesses down to 50 nm. The hierarchical structure consists of two primary arrangements of layers, eutectic colonies of parallel layers, most commonly found at the material interior, and “grains” consisting of alternating Ag and Cu layers which emanate from a central region in a radial pattern, most commonly found at the material exterior surface. We show that the hierarchical structure causes a significant increase in the measured strength response when comparing the Ag 60 Cu 40 response to that of the constituent materials in their bulk nanograined or micrograined form. The deformation mechanisms of this material are studied under compressive loading over the quasi-static and dynamic regime (10 −3 –10 3 s −1 ) with strain between 5% and 50%

  7. Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

    Science.gov (United States)

    Kim, Eun-Min; Yu, Hak Sun; Jin, Yan; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

    2017-08-01

    Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (Psinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system. Copyright © 2016. Published by Elsevier B.V.

  8. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition

    NARCIS (Netherlands)

    Kool, Marcel; Jones, David T. W.; Jäger, Natalie; Northcott, Paul A.; Pugh, Trevor J.; Hovestadt, Volker; Piro, Rosario M.; Esparza, L. Adriana; Markant, Shirley L.; Remke, Marc; Milde, Till; Bourdeaut, Franck; Ryzhova, Marina; Sturm, Dominik; Pfaff, Elke; Stark, Sebastian; Hutter, Sonja; Seker-Cin, Huriye; Johann, Pascal; Bender, Sebastian; Schmidt, Christin; Rausch, Tobias; Shih, David; Reimand, Jüri; Sieber, Laura; Wittmann, Andrea; Linke, Linda; Witt, Hendrik; Weber, Ursula D.; Zapatka, Marc; König, Rainer; Beroukhim, Rameen; Bergthold, Guillaume; van Sluis, Peter; Volckmann, Richard; Koster, Jan; Versteeg, Rogier; Schmidt, Sabine; Wolf, Stephan; Lawerenz, Chris; Bartholomae, Cynthia C.; von Kalle, Christof; Unterberg, Andreas; Herold-Mende, Christel; Hofer, Silvia; Kulozik, Andreas E.; von Deimling, Andreas; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Hasselblatt, Martin; Crawford, John R.; Grant, Gerald A.; Jabado, Nada; Perry, Arie; Cowdrey, Cynthia; Croul, Sydney; Zadeh, Gelareh; Korbel, Jan O.; Doz, Francois; Delattre, Olivier; Bader, Gary D.; McCabe, Martin G.; Collins, V. Peter; Kieran, Mark W.; Cho, Yoon-Jae; Pomeroy, Scott L.; Witt, Olaf; Brors, Benedikt; Taylor, Michael D.; Schüller, Ulrich; Korshunov, Andrey; Eils, Roland; Wechsler-Reya, Robert J.; Lichter, Peter; Pfister, Stefan M.

    2014-01-01

    Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large

  9. Feedback control of primary circulation pump of PIUS-Type reactor

    International Nuclear Information System (INIS)

    Fujii, Mikiya; Anoda, Yoshinari; Murata, Hideo; Yonomoto, Taisuke; Kukita, Yutaka; Tasaka, Kanji.

    1991-05-01

    In operating the PIUS-Type reactor, it is required to keep stationary density interfaces between the primary loop hot water and the poison tank cold, borated water by maintaining pressure balance between the primary-loop and the poison-tank. The authors have developed a primary circulation pump speed control system and tested it in small-scale experiments. This control system regulates the pump speed based on measurements of the density lock differential pressure which is proportional to the elevation of the interface in the density lock. This pump speed control facilitated the normal plant operation which included core power changes. However, the elevation of the density interface indicated oscillatory behavior when the pump speed was regulated as a linear function of the density lock differential pressure. The mechanism responsible for such oscillatory behavior was found to be manometric oscillations that could be eliminated by adding a damping term to compensate for the mechanical delay of the primary pump speed. The passive shutdown function of the reactor was retained by setting an upper limit to the pump speed. This was confirmed in a loss-of-feedwater abnormal transient test. (author)

  10. Pulp tissue response to Portland cement associated with different radio pacifying agents on pulpotomy of human primary molars.

    Science.gov (United States)

    Marques, N; Lourenço Neto, N; Fernandes, A P; Rodini, C; Hungaro Duarte, M; Rios, D; Machado, M A; Oliveira, T

    2015-12-01

    The objective of this research was to evaluate the response of Portland cement associated with different radio pacifying agents on pulp treatment of human primary teeth by clinical and radiographic exams and microscopic analysis. Thirty mandibular primary molars were randomly divided into the following groups: Group I - Portland cement; Group II - Portland cement with iodoform (Portland cement + CHI3 ); Group III - Portland cement with zirconium oxide (Portland cement + ZrO2 ); and treated by pulpotomy technique (removal of a portion of the pulp aiming to maintain the vitally of the remaining radicular pulp tissue using a therapeutic dressing). Clinical and radiographic evaluations were recorded at 6, 12 and 24 months follow-up. The teeth at the regular exfoliation period were extracted and processed for histological analysis. Data were tested using statistical analysis with a significance level of 5%. The microscopic findings were descriptively analysed. All treated teeth were clinically and radiographically successful at follow-up appointments. The microscopic analysis revealed positive response to pulp repair with hard tissue barrier formation and pulp calcification in the remaining roots of all available teeth. The findings of this study suggest that primary teeth pulp tissue exhibited satisfactory biological response to Portland cement associated with radio pacifying agents. However, further studies with long-term follow-up are needed to determine the safe clinical indication of this alternative material for pulp therapy of primary teeth. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  11. 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.

  12. Primary heat transport pump mechanical seal replacement strategy for Pickering B

    International Nuclear Information System (INIS)

    Chacinsi, V.

    1995-01-01

    Pickering Nuclear Generating Station is a CANDU PHWR eight unit station located on Lake Ontario. The station is divided into Pickering A (Units 1 to 4) and Pickering B (Units 5 to 8). Pickering B is the focus of this paper. Each unit is rated at 540 MWe. The Primary Heat Transport (PHT) system, which is used to cool the fuel, is divided into four quadrants. Each quadrant has four vertical Byron Jackson PHT main circulation pumps. Three pumps in each quadrant are required for normal operation, leaving one pump in each quadrant as a spare. Each Pickering PHT pump has a Byron Jackson Type SU two stage mechanical seal. The typical pressure breakdown across the seal is 8.7-4.5-1.0 MPa. Certain features of seal operation and the PHT system which influence seal replacement are discussed below. (author)

  13. Rheological and Mechanical Response Modifications for a Self-Leveling Mortar

    Science.gov (United States)

    Katsiadramis, N. J.; Sotiropoulou, A. B.; Pandermarakis, Z. G.

    2010-06-01

    In many cases cement based materials demand a higher flowability and workability and this conventionally can’t be done without loss of its strength, due to the fact that the common practice to increase the workability is the addition of water. But, nowadays using a third generation superplasticizer (SP) we can achieve the desire flowability without loss of its strength. The action of superplastisizers is to spread efficiently the cement grains and so to wetting better the cement grains giving a more homogeneous mixture with higher strength. Nine different mixtures were prepared adding a small percentage of SP (1%). The conditions to get a self levelling mortar, have to do not only with rheological but also with mechanical demands. The bending and compression test gave the achieving mechanical strength whereas their rheological response came through slump flow and v-funnel flow tests. With the help of a small amount of stabilizer we obtain a robust mixture that deserves the desire response at the field too.

  14. 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

  15. Mechanical response of CH3NH3PbI3 nanowires

    Science.gov (United States)

    Ćirić, L.; Ashby, K.; Abadie, T.; Spina, M.; Duchamp, M.; Náfrádi, B.; Kollár, M.; Forró, L.; Horváth, E.

    2018-03-01

    We report a systematic study of the mechanical response of methylammonium lead triiodide CH3NH3PbI3 nanowires by employing bending measurements using atomic force microscope on suspended wires over photo-lithographically patterned channels. Force-deflection curves measured at room temperature give a Young's modulus between 2 and 14 GPa. This broad range of values is attributed to the variations in the microcrystalline texture of halide perovskite nanowires. The mechanical response of a highly crystalline nanowire is linear with force and has a brittle character. The braking modulus of 48 ± 20 MPa corresponds to 100 μm of radius of curvature of the nanowires, rendering them much better structures for flexible devices than spin coated films. The measured moduli decrease rapidly if the NW is exposed to water vapor.

  16. Barriers to primary care responsiveness to poverty as a risk factor for health.

    Science.gov (United States)

    Bloch, Gary; Rozmovits, Linda; Giambrone, Broden

    2011-06-29

    Poverty is widely recognized as a major determinant of poor health, and this link has been extensively studied and verified. Despite the strong evidentiary link, little work has been done to determine what primary care health providers can do to address their patients' income as a risk to their health. This qualitative study explores the barriers to primary care responsiveness to poverty as a health issue in a well-resourced jurisdiction with near-universal health care insurance coverage. One to one interviews were conducted with twelve experts on poverty and health in primary care in Ontario, Canada. Participants included family physicians, specialist physicians, nurse practitioners, community workers, advocates, policy experts and researchers. The interviews were analysed for anticipated and emergent themes. This study reveals provider- and patient-centred structural, attitudinal, and knowledge-based barriers to addressing poverty as a risk to health. While many of its findings reinforce previous work in this area, this study's findings point to a number of areas front line primary care providers could target to address their patients' poverty. These include a lack of provider understanding of the lived reality of poverty, leading to a failure to collect adequate data about patients' social circumstances, and to the development of inappropriate care plans. Participants also pointed to prejudicial attitudes among providers, a failure of primary care disciplines to incorporate approaches to poverty as a standard of care, and a lack of knowledge of concrete steps providers can take to address patients' poverty. While this study reinforces, in a well-resourced jurisdiction such as Ontario, the previously reported existence of significant barriers to addressing income as a health issue within primary care, the findings point to the possibility of front line primary care providers taking direct steps to address the health risks posed by poverty. The consistent

  17. The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection.

    Directory of Open Access Journals (Sweden)

    Ana Filipovic

    Full Text Available Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1×102, 1×104, and 1×106 inclusion forming units (IFUs. Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4+ and CD8+ cells within guinea pigs' submandibular lymph node (SMLN lymphocytes while the higher doses increased the percentages of CD4+ and CD8+ cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4+ and CD8+ cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1×104, and 1×106 IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections.

  18. Role of genetic polymorphisms in NFKB-mediated inflammatory pathways in response to primary chemoradiation therapy for rectal cancer.

    Science.gov (United States)

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-11-01

    To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Dzhugashvili, Maia; Luengo-Gil, Ginés; García, Teresa; González-Conejero, Rocío; Conesa-Zamora, Pablo; Escolar, Pedro Pablo; Calvo, Felipe; Vicente, Vicente; Ayala de la Peña, Francisco

    2014-01-01

    Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment

  20. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    Directory of Open Access Journals (Sweden)

    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  1. Habituation and sensitization in primary headaches

    Science.gov (United States)

    2013-01-01

    The phenomena of habituation and sensitization are considered most useful for studying the neuronal substrates of information processing in the CNS. Both were studied in primary headaches, that are functional disorders of the brain characterized by an abnormal responsivity to any kind of incoming innocuous or painful stimuli and it’s cycling pattern over time (interictal, pre-ictal, ictal). The present review summarizes available data on stimulus responsivity in primary headaches obtained with clinical neurophysiology. In migraine, the majority of electrophysiological studies between attacks have shown that, for a number of different sensory modalities, the brain is characterised by a lack of habituation of evoked responses to repeated stimuli. This abnormal processing of the incoming information reaches its maximum a few days before the beginning of an attack, and normalizes during the attack, at a time when sensitization may also manifest itself. An abnormal rhythmic activity between thalamus and cortex, namely thalamocortical dysrhythmia, may be the pathophysiological mechanism subtending abnormal information processing in migraine. In tension-type headache (TTH), only few signs of deficient habituation were observed only in subgroups of patients. By contrast, using grand-average responses indirect evidence for sensitization has been found in chronic TTH with increased nociceptive specific reflexes and evoked potentials. Generalized increased sensitivity to pain (lower thresholds and increased pain rating) and a dysfunction in supraspinal descending pain control systems may contribute to the development and/or maintenance of central sensitization in chronic TTH. Cluster headache patients are chrarcterized during the bout and on the headache side by a pronounced lack of habituation of the brainstem blink reflex and a general sensitization of pain processing. A better insight into the nature of these ictal/interictal electrophysiological dysfunctions in primary

  2. On aging factors, aging mechanisms and their combinations in the primary circuit of NPPs

    International Nuclear Information System (INIS)

    Varga, T.; Brumovsky, M.

    1993-01-01

    Ageing is the dominating problem of elder nuclear power plant (NPP) components but still can not be neglected even for the newest ones. Ageing may express itself in different ways: irradiated steel parts may become embrittled, chromium alloy steels may decompose, fatigue life may become exhausted so that cracks may be formed and finally, corrosion attack may result in stress corrosion cracking. However, even synthetics and rubber parts may become inelastic, swell, shrink or crack, electric contacts may be oxydised, or isolations may lose their high electric resistance. Therefore, experts in the different components and their materials have collected and published not only plenty of observations, but also a number of more or less systematic approaches. A general picture, however, still seems to be lacking, due to the fact that ageing factors and mechanisms are not defined and used properly, i.e. - ageing factors act because of the service conditions of the components, as well as the characteristics of the materials which provoke ageing mechanisms - ageing mechanisms cause the changing of properties of the materials involved - combinations of single ageing mechanisms, which can be double, triple or multiple, change and accelerate the ageing process - the consequence of ageing mechanisms is the altering of the properties of the material depending on the lifetime. In this paper we shall try to show a systematic approach to a potential ageing analysis concerning the main metallic components of primary circuits of NPP's - connection between ageing factors, ageing mechanisms and their consequences/effects on component behaviour

  3. Unraveling the mechanism responsible for the contrasting tolerance of Synechocystis and Synechococcus to Cr(VI): Enzymatic and non-enzymatic antioxidants

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Alka [Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Ballal, Anand, E-mail: aballal@barc.gov.in [Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 40085 (India)

    2015-07-15

    Highlights: • Cr(VI) accumulation generates higher ROS in Synechocystis than in Synechococcus. • Synechococcus exhibits better photosynthetic activity in response to Cr(VI). • Synechococcus has higher enzymatic/non-enzymatic antioxidants than Synechocystis. • Synechococcus shows better tolerance to other oxidative stresses than Synechocystis. • Differential detoxification of ROS is responsible for the contrasting tolerance to Cr(VI) - Abstract: Two unicellular cyanobacteria, Synechocystis and Synechococcus, showed contrasting tolerance to Cr(VI); with Synechococcus being 12-fold more tolerant than Synechocystis to potassium dichromate. The mechanism responsible for this differential sensitivity to Cr(VI) was explored in this study. Total content of photosynthetic pigments as well as photosynthetic activity decreased at lower concentration of Cr(VI) in Synechocystis as compared to Synechococcus. Experiments with {sup 51}Cr showed Cr to accumulate intracellularly in both the cyanobacteria. At lower concentrations, Cr(VI) caused excessive ROS generation in Synechocystis as compared to that observed in Synechococcus. Intrinsic levels of enzymatic antioxidants, i.e., superoxide dismutase, catalase and 2-Cys-peroxiredoxin were considerably higher in Synechococcus than Synechocystis. Content of total thiols (both protein as well as non-protein) and reduced glutathione (GSH) was also higher in Synechococcus as compared to Synechocystis. This correlated well with higher content of carbonylated proteins observed in Synechocystis than Synechococcus. Additionally, in contrast to Synechocystis, Synechococcus exhibited better tolerance to other oxidative stresses like high intensity light and H{sub 2}O{sub 2}. The data indicate that the disparity in the ability to detoxify ROS could be the primary mechanism responsible for the differential tolerance of these cyanobacteria to Cr(VI)

  4. Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

    Directory of Open Access Journals (Sweden)

    Wassila Ouelaa

    Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

  5. Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination

    DEFF Research Database (Denmark)

    Kongsgaard, Michael; Bassi, Maria Rosaria; Rasmussen, Michael

    2017-01-01

    Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single...... vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong...... cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination...

  6. 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

  7. 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.

  8. 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.

  9. Mechanisms of cross-suppression of TNP-specific plaque forming cell responses by TMA-specific first-order T suppressor factor

    Energy Technology Data Exchange (ETDEWEB)

    Jendrisak, G.S.; Bellone, C.J.

    1986-03-05

    The addition of hybridoma-derived phenyltrimethylammonium (TMA)-specific first-order T suppressor factor (TsF/sub 1/) into cultures containing Brucella abortus coupled with the TMA and trinitrophenol haptens (TMA-BA-TNP) results in the cross-suppression of TNP-specific plaque forming cell (PFC) responses. The suppression mediated by TMA-TsF/sub 1/ is dependent on the presence of T cells and specific antigen (TMA). Subculturing of whole spleen cells with TMA-TsF/sub 1/ and specific soluble antigen (TMA-BSA) is able to induce suppressor T cells which cross-suppress the TNP-specific PFC of spleen cell cultures stimulated with TMA-BA-TNP in an antigen (TMA)-dependent manner at the effector phase of the response. The effector acting T suppressor cells (Tse) are nylon wool nonadherent and appears to require whole spleen cells in responding cultures for suppression, suggesting that the target of the Tse is not the TNP-specific B cell. The authors are presently characterizing the mechanisms of cross-suppression by TMA-TsF/sub 1/ and Tse utilizing the described primary in vitro antibody assay.

  10. Acquired immunodeficiency syndrome-related primary cerebral lymphoma: response to irradiation

    International Nuclear Information System (INIS)

    Khoo, V.S.; Wilson, P.C.; Sexton, M.J.; Liew, K.H.

    2000-01-01

    Acquired immunodeficiency syndrome-related primary cerebral lymphoma (AIDS-PCL) is uncommon. Fourteen cases of presumed AIDS-PCL between 1986 and 1995 were reviewed retrospectively in order to characterize the natural history, and the response to radiotherapy. The median age was 38 years (range 24-65). The median interval between seropositive diagnosis of HIV and AIDS-PCL was 28 months (range 5-113). The median duration of symptoms was 2 weeks (range 0.2-12). At presentation, the Eastern Cooperative Oncology Group performance status (PS) was PS1 (2/14 patients), PS2 (6/14) and PS3 (6/14). The symptoms and signs were non-specific and depended on the site and extent of cerebral involvement. There was no characteristic pattern of brain imaging in terms of size, number, location or pattern of contrast enhancement of the cerebral lesions. Nine patients received various fractionation-dose schedules (range 8-50 Gy). Complete and partial responses were seen in 2/9 and 3/9 cases, respectively. Clinical stabilization of neurological symptoms was noted in 3/9 cases and disease progression in 1/9. The median survival times (MST) from presentation for irradiated and non-irradiated patients were 9.3 and 2.1 weeks, respectively (range 0.9-43.1). Although patient selection introduced bias, there appears to be a modest improvement in MST for treated patients. The MST with radiotherapy alone remains poor, but radiotherapy may provide palliation. For some selected patients, a prolonged response is possible. Copyright (1999) Blackwell Science Pty Ltd

  11. 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

  12. The use of clinical practice guidelines in primary care: professional mindlines and control mechanisms.

    Science.gov (United States)

    Gené-Badia, Joan; Gallo, Pedro; Caïs, Jordi; Sánchez, Emília; Carrion, Carme; Arroyo, Liliana; Aymerich, Marta

    2016-01-01

    To identify the relevant barriers and enablers perceived by primary care professionals in implementing the recommendations of clinical practice guidelines (CPG). Two focus groups were conducted with primary care physicians and nurses in Catalonia (Spain) between October and December 2012. Thirty-nine health professionals were selected based on their knowledge and daily use of CPG. Finally, eight general practitioners and eight nurses were included in the discussion groups. Participants were asked to share their views and beliefs on the accessibility of CPG, their knowledge and use of these documents, the content and format of CPG, dissemination strategy, training, professional-patient relationship, and the use of CPG by the management structure. We recorded and transcribed the content verbatim and analysed the data using qualitative analysis techniques. Physicians believed that, overall, CPG were of little practical use and frequently referred to them as a largely bureaucratic management control instrument that threatened their professional autonomy. In contrast, nurses believed that CPG were rather helpful tools in their day-to-day practice, although they would like them to be more sensitive to the current role of nurses. Both groups believed that CPG did not provide a response to most of the decisions they faced in the primary care setting. Compliance with CPG recommendations would be improved if these documents were brief, non-compulsory, not cost-containment oriented, more based on nursing care models, sensitive to the specific needs of primary care patients, and integrated into the computer workstation. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Rheological and Mechanical Response Modifications for a Self-Leveling Mortar

    Directory of Open Access Journals (Sweden)

    Pandermarakis Z.G.

    2010-06-01

    Full Text Available In many cases cement based materials demand a higher flowability and workability and this conventionally can’t be done without loss of its strength, due to the fact that the common practice to increase the workability is the addition of water. But, nowadays using a third generation superplasticizer (SP we can achieve the desire flowability without loss of its strength. The action of superplastisizers is to spread efficiently the cement grains and so to wetting better the cement grains giving a more homogeneous mixture with higher strength. Nine different mixtures were prepared adding a small percentage of SP (1%. The conditions to get a self levelling mortar, have to do not only with rheological but also with mechanical demands. The bending and compression test gave the achieving mechanical strength whereas their rheological response came through slump flow and v-funnel flow tests. With the help of a small amount of stabilizer we obtain a robust mixture that deserves the desire response at the field too.

  14. 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....

  15. Mechanisms of Response to Salt Stress in Oleander (Nerium oleander L.

    Directory of Open Access Journals (Sweden)

    Dinesh Kumar

    2016-11-01

    Full Text Available Elucidating the mechanisms of abiotic stress tolerance in different species will help to develop more resistant plant varieties, contributing to improve agricultural production in a climate change scenario. Basic responses to salt stress, dependent on osmolyte accumulation and activation of antioxidant systems, have been studied in Nerium oleander, a xerophytic species widely used as ornamental. Salt strongly inhibited growth, but the plants survived one-month treatments with quite high NaCl concentrations, up to 800 mM, indicating the the species is relatively resistant to salt stress, in addition to drought. Levels of proline, glycine betaine and soluble sugars increased only slightly in the presence of salt; however, soluble sugar absolute contents were much higher than those of the other osmolytes, suggesting a functional role of these compounds in osmotic adjustment, and the presence of constitutive mechanisms of response to salt stress. High salinity generated oxidative stress in the plants, as shown by the increase of malondialdehyde levels. Antioxidant systems, enzymatic and non-enzymatic, are generally activated in response to salt stress; in oleander, they do not seem to include total phenolics or flavonoids, antioxidant compounds which did not accumulate significantly in salt-trated plants

  16. 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)

  17. 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.

  18. Sleep disorders associated with primary mitochondrial diseases.

    Science.gov (United States)

    Ramezani, Ryan J; Stacpoole, Peter W

    2014-11-15

    Primary mitochondrial diseases are caused by heritable or spontaneous mutations in nuclear DNA or mitochondrial DNA. Such pathological mutations are relatively common in humans and may lead to neurological and neuromuscular complication that could compromise normal sleep behavior. To gain insight into the potential impact of primary mitochondrial disease and sleep pathology, we reviewed the relevant English language literature in which abnormal sleep was reported in association with a mitochondrial disease. We examined publication reported in Web of Science and PubMed from February 1976 through January 2014, and identified 54 patients with a proven or suspected primary mitochondrial disorder who were evaluated for sleep disturbances. Both nuclear DNA and mitochondrial DNA mutations were associated with abnormal sleep patterns. Most subjects who underwent polysomnography had central sleep apnea, and only 5 patients had obstructive sleep apnea. Twenty-four patients showed decreased ventilatory drive in response to hypoxia and/ or hyperapnea that was not considered due to weakness of the intrinsic muscles of respiration. Sleep pathology may be an underreported complication of primary mitochondrial diseases. The probable underlying mechanism is cellular energy failure causing both central neurological and peripheral neuromuscular degenerative changes that commonly present as central sleep apnea and poor ventilatory response to hyperapnea. Increased recognition of the genetics and clinical manifestations of mitochondrial diseases by sleep researchers and clinicians is important in the evaluation and treatment of all patients with sleep disturbances. Prospective population-based studies are required to determine the true prevalence of mitochondrial energy failure in subjects with sleep disorders, and conversely, of individuals with primary mitochondrial diseases and sleep pathology. © 2014 American Academy of Sleep Medicine.

  19. 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.

  20. Correlation Factors Describing Primary and Spatial Sensations of Sound Fields

    Science.gov (United States)

    ANDO, Y.

    2002-11-01

    The theory of subjective preference of the sound field in a concert hall is established based on the model of human auditory-brain system. The model consists of the autocorrelation function (ACF) mechanism and the interaural crosscorrelation function (IACF) mechanism for signals arriving at two ear entrances, and the specialization of human cerebral hemispheres. This theory can be developed to describe primary sensations such as pitch or missing fundamental, loudness, timbre and, in addition, duration sensation which is introduced here as a fourth. These four primary sensations may be formulated by the temporal factors extracted from the ACF associated with the left hemisphere and, spatial sensations such as localization in the horizontal plane, apparent source width and subjective diffuseness are described by the spatial factors extracted from the IACF associated with the right hemisphere. Any important subjective responses of sound fields may be described by both temporal and spatial factors.

  1. Cellular Mechanics of Primary Human Cervical Fibroblasts: Influence of Progesterone and a Pro-inflammatory Cytokine.

    Science.gov (United States)

    Shukla, Vasudha; Barnhouse, Victoria; Ackerman, William E; Summerfield, Taryn L; Powell, Heather M; Leight, Jennifer L; Kniss, Douglas A; Ghadiali, Samir N

    2018-01-01

    The leading cause of neonatal mortality, pre-term birth, is often caused by pre-mature ripening/opening of the uterine cervix. Although cervical fibroblasts play an important role in modulating the cervix's extracellular matrix (ECM) and mechanical properties, it is not known how hormones, i.e., progesterone, and pro-inflammatory insults alter fibroblast mechanics, fibroblast-ECM interactions and the resulting changes in tissue mechanics. Here we investigate how progesterone and a pro-inflammatory cytokine, IL-1β, alter the biomechanical properties of human cervical fibroblasts and the fibroblast-ECM interactions that govern tissue-scale mechanics. Primary human fibroblasts were isolated from non-pregnant cervix and treated with estrogen/progesterone, IL-1β or both. The resulting changes in ECM gene expression, matrix remodeling, traction force generation, cell-ECM adhesion and tissue contractility were monitored. Results indicate that IL-1β induces a significant reduction in traction force and ECM adhesion independent of pre-treatment with progesterone. These cell level effects altered tissue-scale mechanics where IL-1β inhibited the contraction of a collagen gel over 6 days. Interestingly, progesterone treatment alone did not modulate traction forces or gel contraction but did result in a dramatic increase in cell-ECM adhesion. Therefore, the protective effect of progesterone may be due to altered adhesion dynamics as opposed to altered ECM remodeling.

  2. The different response mechanisms of Wolffia globosa: Light-induced silver nanoparticle toxicity

    International Nuclear Information System (INIS)

    Zou, Xiaoyan; Li, Penghui; Huang, Qing; Zhang, Hongwu

    2016-01-01

    Highlights: • The different physiological responses of AgNPs in Wolffia golbosa were studied. • Effects of AgNPs on W. golbosa relied on the illumination conditions. • Different phytotoxic mechanisms of AgNPs for different light schemes were proposed. - Abstract: Silver nanoparticles (AgNPs) have emerged as a promising bactericide. Plants are a major point of entry of contaminants into trophic chains. Here, the physiological responses of Wolffia globosa to AgNPs have been probed using different light schemes, and these data may reveal new insights into the toxic mechanism of AgNPs. W. globosa was grown in culture medium and treated with different concentrations of AgNPs for 24 h under pre- and post-illuminated conditions. However, fluorescence quenching, the accumulation of sugar and the reduction of Hill reaction activity were found in response to the AgNP-stresses. In the pre-illuminated condition, oxidative damage was obvious, as indicated by the higher malondialdehyde (MDA) content and an up-regulation of superoxide dismutase (SOD) activity. The maximum increases of MDA content and SOD activity were 1.14 and 2.52 times the respective controls when exposed to 10 mg/L AgNPs. In contrast, in the post-illuminated condition, the alterations in photosynthetic pigment and soluble proteins content were more significant than the alterations in oxidative stress. The contents of chlorophyll a, carotenoids and soluble protein decreased to 77.7%, 66.2% and 72.9% of the controls after treatment with the highest concentration of AgNPs (10 mg/L). Based on the different physiological responses, we speculated that in the pre-illuminated condition, oxidative stress was responsible for the decline in the oxygen evolution rate, while in the post-illuminated condition, the decrease in the Hill reaction activity could be attributed to the blocking of electron transfer and an insufficient proton supply. Our findings demonstrate that environmental factors regulate the

  3. The different response mechanisms of Wolffia globosa: Light-induced silver nanoparticle toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Xiaoyan; Li, Penghui [Key Laboratory of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen (China); Huang, Qing [Key Laboratory of Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen (China); Zhang, Hongwu, E-mail: hwzhang@iue.ac.cn [Key Laboratory of Urban Pollutant Conversion, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen (China); Ningbo Research Center for Urban Environment, Chinese Academy of Sciences, Ningbo (China)

    2016-07-15

    Highlights: • The different physiological responses of AgNPs in Wolffia golbosa were studied. • Effects of AgNPs on W. golbosa relied on the illumination conditions. • Different phytotoxic mechanisms of AgNPs for different light schemes were proposed. - Abstract: Silver nanoparticles (AgNPs) have emerged as a promising bactericide. Plants are a major point of entry of contaminants into trophic chains. Here, the physiological responses of Wolffia globosa to AgNPs have been probed using different light schemes, and these data may reveal new insights into the toxic mechanism of AgNPs. W. globosa was grown in culture medium and treated with different concentrations of AgNPs for 24 h under pre- and post-illuminated conditions. However, fluorescence quenching, the accumulation of sugar and the reduction of Hill reaction activity were found in response to the AgNP-stresses. In the pre-illuminated condition, oxidative damage was obvious, as indicated by the higher malondialdehyde (MDA) content and an up-regulation of superoxide dismutase (SOD) activity. The maximum increases of MDA content and SOD activity were 1.14 and 2.52 times the respective controls when exposed to 10 mg/L AgNPs. In contrast, in the post-illuminated condition, the alterations in photosynthetic pigment and soluble proteins content were more significant than the alterations in oxidative stress. The contents of chlorophyll a, carotenoids and soluble protein decreased to 77.7%, 66.2% and 72.9% of the controls after treatment with the highest concentration of AgNPs (10 mg/L). Based on the different physiological responses, we speculated that in the pre-illuminated condition, oxidative stress was responsible for the decline in the oxygen evolution rate, while in the post-illuminated condition, the decrease in the Hill reaction activity could be attributed to the blocking of electron transfer and an insufficient proton supply. Our findings demonstrate that environmental factors regulate the

  4. Effects and mechanisms of Shaofu-Zhuyu decoction and its major bioactive component for Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats.

    Science.gov (United States)

    Huang, Xiaochen; Su, Shulan; Duan, Jin-Ao; Sha, Xiuxiu; Zhu, Kavin Yue; Guo, Jianming; Yu, Li; Liu, Pei; Shang, Erxin; Qian, Dawei

    2016-06-20

    Traditional Chinese medicine (TCM) is used under the guidance of the theory of traditional Chinese medical sciences in clinical application. The Chinese herbal formula, Shaofu Zhuyu decoction (SFZYD), is considered as an effective prescription for treating Cold - Stagnation and Blood - Stasis (CSBS) primary dysmenorrhea. The previous studies showed the SFZYD exhibited significant anti-inflammation and analgesic effect. In this present study the metabolomics of CSBS primary dysmenorrhea diseased rats and the cytokine transcription in PHA stimulated-PBMC were investigated to explore the effects and mechanisms. Explore a valuable insight into the effects and mechanisms of SFZYD on Cold - Stagnation and Blood - Stasis primary dysmenorrhea rats. We established CSBS primary dysmenorrhea diseased rats according the clinical symptoms. A targeted tandem mass spectrometry (MS/MS)-based metabolomic platform was used to evaluate the metabolic profiling changes and the intervention effects by SFZYD. The PBMC cell was adopted to explore the mechanisms by analyzing the signaling pathway evaluated by expression of inflammatory cytokines, c-jun and c-fos and corresponding phosphorylation levels. Estradiol, oxytocin, progesterone, endothelin, β-endorphin and PGF2α were restored back to the normal level after the treatment of SFZYD. Total twenty-five metabolites (10 in plasma and 15 in urine), up-regulated or down-regulated, were identified. These identified biomarkers underpinning the metabolic pathway including pentose and glucuronate interconversions, steroid hormone biosynthesis, and glycerophospholipid metabolism are disturbed in model rats. Among these metabolites, twenty one potential biomarkers were regulated after SFZYD treated. The compound of paeoniflorin, a major bioactive compound in SFZYD, was proved to regulate the MAPK signaling pathway by inhibiting the expression of IL-1β, IL-2, IL-10, IL-12, TNFα, INFγ, c-jun and c-fos in PHA stimulated-PBMC. These findings

  5. Primary cilia utilize glycoprotein-dependent adhesion mechanisms to stabilize long-lasting cilia-cilia contacts

    Directory of Open Access Journals (Sweden)

    Ott Carolyn

    2012-04-01

    Full Text Available Abstract Background The central tenet of cilia function is sensing and transmitting information. The capacity to directly contact extracellular surfaces would empower primary cilia to probe the environment for information about the nature and location of nearby surfaces. It has been well established that flagella and other motile cilia perform diverse cellular functions through adhesion. We hypothesized that mammalian primary cilia also interact with the extracellular environment through direct physical contact. Methods We identified cilia in rod photoreceptors and cholangiocytes in fixed mouse tissues and examined the structures that these cilia contact in vivo. We then utilized an MDCK cell culture model to characterize the nature of the contacts we observed. Results In retina and liver tissue, we observed that cilia from nearby cells touch one another. Using MDCK cells, we found compelling evidence that these contacts are stable adhesions that form bridges between two cells, or networks between many cells. We examined the nature and duration of the cilia-cilia contacts and discovered primary cilia movements that facilitate cilia-cilia encounters. Stable adhesions form as the area of contact expands from a single point to a stretch of tightly bound, adjacent cilia membranes. The cilia-cilia contacts persisted for hours and were resistant to several harsh treatments such as proteases and DTT. Unlike many other cell adhesion mechanisms, calcium was not required for the formation or maintenance of cilia adhesion. However, swainsonine, which blocks maturation of N-linked glycoproteins, reduced contact formation. We propose that cellular control of adhesion maintenance is active because cilia adhesion did not prevent cell division; rather, contacts dissolved during mitosis as cilia were resorbed. Conclusions The demonstration that mammalian primary cilia formed prolonged, direct, physical contacts supports a novel paradigm: that mammalian primary

  6. Breast conserving surgery following primary irradiation in 3-7 cm breast cancer: pathologic response and outcome

    International Nuclear Information System (INIS)

    Saint-Gaudens, Anne Bareille; Vilcoq, Jacques R.; Campana, Francois; Gautier, Chantal; Asselain, Bernard; Rocherfordiere, Anne de la; Clough, Krishna B.; Fourquet, Alain

    1997-01-01

    Purpose: To retrospectively evaluate histologic response and outcome of patients treated by primary irradiation followed by conservative surgery. Materials and Methods: Between 1981 and 1993, 1742 patients (pts.) with large 3-7 cm invasive breast cancer were treated by primary breast and nodes irradiation in our institution. Of these, 311 pts. (18%) further underwent a wide excision of the residual tumor. Median age was 55 years (yrs.) (29 - 79 yrs.). Median breast tumor size was 40 mm (35 - 70mm). 149 pts. (48%) were premenopausal. 142 pts (46%) had clinically palpable axillary nodes. Diagnosis of invasive breast cancer was performed in all patients by drill biopsy. Following diagnosis, all 311 patients were treated by external irradiation to the breast and regional nodes. Median dose to the breast was 55 Gy (50 - 64 Gy) over 5.5 weeks. Following this irradiation, all patients underwent a wide surgical excision with (140 pts; 45%) or without (171 pts; 55%) axillary node dissection. In addition, 70 pts (22.5%) received adjuvant chemotherapy and 70 pts. received hormone therapy after local treatment. All patients were then regularly followed. Results: Median residual breast tumor size after completion of irradiation was 20 mm (0 - 50mm). On pathologic examination, 34 (11%) tumors had no residual malignant cells (complete response), 137 tumors (44%) had residual fibrosis with clusters of viable cells (partial response), and 138 tumors (45%) had residual viable malignant cells (no response). Median follow up was 106 months (10 - 188 months). Actuarial 9-year overall survival rate was 69 % ± 6%. The 9-year metastasis-free interval was 58 % ± 6%. The 9-year breast recurrence rate was 22 % ± 5 %. The 9-year breast preservation rate was 84% ± 5%. Pathologic response was not predictive of outcome, either distant or local. Conclusion: This retrospective study showed that in patients with tumors too large to be treated by upfront breast-conserving surgery, primary breast

  7. Metallurgical and mechanical parameters controlling alloy 718 stress corrosion cracking resistance in PWR primary water

    International Nuclear Information System (INIS)

    Deleume, J.

    2007-11-01

    Improving the performance and reliability of the fuel assemblies of the pressurized water reactors requires having a perfect knowledge of the operating margins of both the components and the materials. The choice of alloy 718 as reference material for this study is justified by the industrial will to identify the first order parameters controlling the excellent resistance of this alloy to Stress Corrosion Cracking (SCC). For this purpose, a specific slow strain rate (SSR) crack initiation test using tensile specimen with a V-shaped hump in the middle of the gauge length was developed and modeled. The selectivity of such SSR tests in simulated PWR primary water at 350 C was clearly established by characterizing the SCC resistance of nine alloy 718 thin strip heats. Regardless of their origin and in spite of a similar thermo-mechanical history, they did not exhibit the same susceptibility to SCC crack initiation. All the characterized alloy 718 heats develop oxide scale of similar nature for various exposure times to PWR primary medium in the temperature range [320 C - 360 C]. δ phase precipitation has no impact on alloy 718 SCC initiation behavior when exposed to PWR primary water, contrary to interstitial contents and the triggering of plastic instabilities (PLC phenomenon). (author)

  8. Changes in primary productivity and chlorophyll a in response to iron fertilization in the Southern Polar Frontal Zone

    OpenAIRE

    Gervais, F.; Riebesell, Ulf; Gorbunov, MY

    2002-01-01

    EisenEx�the second in situ iron enrichment experiment in the Southern Ocean�was performed in the Atlantic sector over 3 weeks in November 2000 with the overarching goal to test the hypothesis that primary productivity in the Southern Ocean is limited by iron availability in the austral spring. Underwater irradiance, chlorophyll a (Chl a), photochemical efficiency, and primary productivity were measured inside and outside of an iron-enriched patch in order to quantify the response of phytoplan...

  9. Evasion of adaptive and innate immune response mechanisms by γ-herpesviruses

    Science.gov (United States)

    Feng, Pinghui; Moses, Ashlee; Früh, Klaus

    2015-01-01

    γ-Herpesviral immune evasion mechanisms are optimized to support the acute, lytic and the longterm, latent phase of infection. During acute infection, specific immune modulatory proteins limit, but also exploit, the antiviral activities of cell intrinsic innate immune responses as well as those of innate and adaptive immune cells. During latent infection, a restricted gene expression program limits immune targeting and cis-acting mechanisms to reduce the antigen presentation as well as antigenicity of latency-associated proteins. Here, we will review recent progress in our understanding of γ-herpesviral immune evasion strategies. PMID:23735334

  10. Micromechanical Models of Mechanical Response of High Performance Fibre Reinforced Cement Composites

    DEFF Research Database (Denmark)

    Li, V. C.; Mihashi, H.; Alwan, J.

    1996-01-01

    generation of FRC with high performance and economical viability, is in sight. However, utilization of micromechanical models for a more comprehensive set of important HPFRCC properties awaits further investigations into fundamental mechanisms governing composite properties, as well as intergrative efforts......The state-of-the-art in micromechanical modeling of the mechanical response of HPFRCC is reviewed. Much advances in modeling has been made over the last decade to the point that certain properties of composites can be carefully designed using the models as analytic tools. As a result, a new...... across responses to different load types. Further, micromechanical models for HPFRCC behavior under complex loading histories, including those in fracture, fatigue and multuaxial loading are urgently needed in order to optimize HPFRCC microstrcuctures and enable predictions of such material in structures...

  11. Improvement of Soybean Products Through the Response Mechanism Analysis Using Proteomic Technique.

    Science.gov (United States)

    Wang, Xin; Komatsu, Setsuko

    Soybean is rich in protein/vegetable oil and contains several phytochemicals such as isoflavones and phenolic compounds. Because of the predominated nutritional values, soybean is considered as traditional health benefit food. Soybean is a widely cultivated crop; however, its growth and yield are markedly affected by adverse environmental conditions. Proteomic techniques make it feasible to map protein profiles both during soybean growth and under unfavorable conditions. The stress-responsive mechanisms during soybean growth have been uncovered with the help of proteomic studies. In this review, the history of soybean as food and the morphology/physiology of soybean are described. The utilization of proteomics during soybean germination and development is summarized. In addition, the stress-responsive mechanisms explored using proteomic techniques are reviewed in soybean. © 2017 Elsevier Inc. All rights reserved.

  12. Extracting material response from simple mechanical tests on hardening-softening-hardening viscoplastic solids

    Science.gov (United States)

    Mohan, Nisha

    Compliant foams are usually characterized by a wide range of desirable mechanical properties. These properties include viscoelasticity at different temperatures, energy absorption, recoverability under cyclic loading, impact resistance, and thermal, electrical, acoustic and radiation-resistance. Some foams contain nano-sized features and are used in small-scale devices. This implies that the characteristic dimensions of foams span multiple length scales, rendering modeling their mechanical properties difficult. Continuum mechanics-based models capture some salient experimental features like the linear elastic regime, followed by non-linear plateau stress regime. However, they lack mesostructural physical details. This makes them incapable of accurately predicting local peaks in stress and strain distributions, which significantly affect the deformation paths. Atomistic methods are capable of capturing the physical origins of deformation at smaller scales, but suffer from impractical computational intensity. Capturing deformation at the so-called meso-scale, which is capable of describing the phenomenon at a continuum level, but with some physical insights, requires developing new theoretical approaches. A fundamental question that motivates the modeling of foams is `how to extract the intrinsic material response from simple mechanical test data, such as stress vs. strain response?' A 3D model was developed to simulate the mechanical response of foam-type materials. The novelty of this model includes unique features such as the hardening-softening-hardening material response, strain rate-dependence, and plastically compressible solids with plastic non-normality. Suggestive links from atomistic simulations of foams were borrowed to formulate a physically informed hardening material input function. Motivated by a model that qualitatively captured the response of foam-type vertically aligned carbon nanotube (VACNT) pillars under uniaxial compression [2011,"Analysis of

  13. 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...

  14. Immune response and anamnestic immune response in children after a 3-dose primary hepatitis b vaccination

    International Nuclear Information System (INIS)

    Afzal, M.F.; Sultan, M.A.; Saleemi, A.I.

    2017-01-01

    Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response and anamnestic immune response in children, 9 months-10 years of age, after a 3-dose primary Hepatitis B vaccination. Methods: This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, docu mented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum anti-HBsAb by ELIZA was measured. Children with anti-HBs titers =10 mIU/mL were considered to be immune. Those with anti-HBsAb levels <10 mIU/mL were offered a booster dose of infant recombinant hepatitis B vaccine. The second serum sample was obtained 21-28 days following the administration of the booster dose and the anamnestic immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Results: Of the 200 children, protective antibody response was found in 58 percent. Median serological response was 18.60 (range 2.82-65.15). Antibody levels were found to have a statistically significant (p-value 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vaccine was administered to all non-responders, with each registering a statistically significant (p-value 0.00) anamnestic response. Conclusion: The vaccination schedule with short dosage interval was unable to provide

  15. 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)

  16. 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...

  17. The response to Typhi Vi vaccination is compromised in individuals with primary immunodeficiency.

    Science.gov (United States)

    Kumarage, Jeevani; Seneviratne, Suranjith L; Senaratne, Vijitha; Fernando, Amitha; Gunasekera, Kirthi; Gunasena, Bandu; Gurugama, Padmalal; Peiris, Sudath; Parker, Antony R; Harding, Stephen; de Silva, Nilhan Rajiva

    2017-06-01

    Measurement of an individuals ability to respond to polysaccharide antigens is a crucial test to determine adaptive immunity. Currently the response to Pneumovax ® is utilized but with the success of Prevnar ® , measurement of the response to Pneumovax may be challenging. The aim of the study was to assess the response to Typhi Vi vaccination in both children and adult control groups and patients with primary immunodeficiency (PID). In the control groups, >95% of the individuals had pre Typhi Vi vaccination concentrations 94% achieving ≥3 fold increase in concentration (FI). The response to Typhi Vi vaccination was significantly lower in both children ( p = 0.006) and adult ( p = 0.002) PID groups when compared to their control groups. 11% and 55% of the children and adult PID groups respectively did not obtain a response >3FI. There were no significant differences between the responses obtained in the children and adult PID groups. When all individuals with PID were separated into those with either hypogammaglobulinemia (HYPO) or common variable immunodeficiency (CVID), both groups had a significantly lower median FI than the control group (19, 95%CI 5-56 vs 59, 95%CI 7-237; p = 0.01 and 1, 95%CI 1-56 vs 32, 95%CI 5-136; p = 0.005). Further, a >3FI differentiated the antibody responses between both the CVID and HYPO groups and their control groups (AUC: 0.83, 95%CI: 0.65-1.00, p = 0.005 and 0.81, 95% CI: 0.65-0.97, p = 0.01). The data suggests that measurement of the response to Typhi Vi vaccination could represent a complementary assay for the assessment of the response to a polysaccharide vaccine.

  18. Response of EBR-II to a complete loss of primary forced flow during power operation

    International Nuclear Information System (INIS)

    Singer, R.M.; Gillette, J.L.; Mohr, D.; Tokar, J.V.; Sullivan, J.E.; Dean, E.M.

    1980-01-01

    Detailed measurements of the thermal, hydraulic, and neutronic response of EBR-II to a complete loss of primary forced flow followed by a PPS-activated scram are presented. The experimental results clearly indicate a smooth transition to natural convective flow with a quite modest incore temperature transient. The accompanying calculations using the NATDEMO code agree quite well with the measured temperatures and flow rates throughout the primary system. The only region of the plant where a significant discrepancy between the measurements and calculations occurred was in the IHX. The reasons for this result could not be definitively determined, but it is speculated that the one-dimensional assumptions used in the modeling may not be valid in the IHX during buoyancy driver flows

  19. Testosterone has a long-term effect on primary sex ratio of first eggs in pigeons-in search of a mechanism

    NARCIS (Netherlands)

    Goerlich, V. C.; Dijkstra, C.; Schaafsma, S. M.; Groothuis, T. G. G.

    2009-01-01

    Despite accumulating evidence that birds, in which females are the heterogametic sex, are able to manipulate primary offspring sex ratio, the underlying mechanism remains elusive. Steroid hormones. which govern female reproduction and are also accumulated by the developing follicle could potentially

  20. Bridging miles to achieve milestones: Corporate social responsibility for primary health care.

    Science.gov (United States)

    Gulati, Ruchie

    2017-01-01

    Sustainable Developmental Goals aim to provide "Good health for all". The task though immense ,requires equitable and efficient distribution of health resources to the community, reached predominantly by the Primary Health Centres. Strengthening these centres is essential to attain the goal. Adequate health financing is one of the important determinants for utilizing the optimal potential of these centres . Pooling funds from alternate financing strategies as Corporate Social Responsibility (CSR) funds may give impetus and facilitate healthcare affordability to the underserved population. This convergence of vision of corporate funding for "basic health services" may bridge the gap arising out of inadequate funding and facilitate "Good Health for all" in India.

  1. 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.

  2. Different Response to Nivolumab in a Patient with Synchronous Double Primary Carcinomas of Hypopharyngeal Cancer and Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Teppei Yamaguchi

    2017-09-01

    Full Text Available Nivolumab is a humanized IgG4 and programmed death 1 (PD-1 monoclonal antibody that has demonstrated antitumor efficacy in clinical trials of various malignant tumors including non-small-cell lung cancer and head and neck squamous cell carcinoma (SCC. However, patients with multiple primary malignancies were excluded in clinical trials. Thus, the efficacy of nivolumab in such patients has not been revealed yet. The programmed death ligand 1 (PD-L1 expression level is currently the main predictive biomarker of PD-1 inhibitors in various types of solid tumors and hematological malignancies. Here we describe a patient with synchronous double primary carcinomas of hypopharyngeal SCC and lung adenocarcinoma who exhibited different responses to nivolumab. After nivolumab treatment, hypopharyngeal SCC with moderate PD-L1 positivity by immunohistochemical staining showed a remarkable response; conversely, nivolumab was not effective against lung adenocarcinoma, which was negative for PD-L1. This suggests that tumors with different PD-L1 expressions may exhibit different responses to PD-1 inhibitors when multiple primary malignancies are present within one patient.

  3. Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation

    Directory of Open Access Journals (Sweden)

    Simone P. Sittig

    2015-12-01

    Full Text Available Dendritic cell (DC-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c+ and CD141+ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies.

  4. 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.

  5. Hydrogen absorption mechanisms and hydrogen interactions - defects: implications to stress corrosion of nickel based alloys in pressurized water reactors primary water

    International Nuclear Information System (INIS)

    Jambon, F.

    2012-01-01

    Since the late 1960's, a special form of stress corrosion cracking (SCC) has been identified for Alloy 600 exposed to pressurized water reactors (PWR) primary water: intergranular cracks develop during the alloy exposure, leading, progressively, to the complete ruin of the structure, and to its replacement. The main goal of this study is therefore to evaluate in which proportions the hydrogen absorbed by the alloy during its exposure to the primary medium can be responsible for SCC crack initiation and propagation. This study is aimed at better understanding of the hydrogen absorption mechanism when a metallic surface is exposed to a passivating PWR primary medium. A second objective is to characterize the interactions of the absorbed hydrogen with the structural defects of the alloy (dislocations, vacancies...) and evaluate to what extent these interactions can have an embrittling effect in relation with SCC phenomenon. Alloy 600-like single-crystals were exposed to a simulated PWR medium where the hydrogen atoms of water or of the pressuring hydrogen gas were isotopically substituted with deuterium, used as a tracer. Secondary ion mass spectrometry depth-profiling of deuterium was performed to characterize the deuterium absorption and localization in the passivated alloy. The results show that the hydrogen absorption during the exposure of the alloy to primary water is associated with the water molecules dissociation during the oxide film build-up. In an other series of experiments, structural defects were created in recrystallized samples, and finely characterized by positron annihilation spectroscopy and transmission electron microscopy, before or after the introduction of cathodic hydrogen. These analyses exhibited a strong hydrogen/defects interaction, evidenced by their structural reorganization under hydrogenation (coalescence, migrations). However, thermal desorption spectroscopy analyses indicated that these interactions are transitory, and dependent on

  6. 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.

  7. 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...

  8. 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)

  9. Response mechanism for surface acoustic wave gas sensors based on surface-adsorption.

    Science.gov (United States)

    Liu, Jiansheng; Lu, Yanyan

    2014-04-16

    A theoretical model is established to describe the response mechanism of surface acoustic wave (SAW) gas sensors based on physical adsorption on the detector surface. Wohljent's method is utilized to describe the relationship of sensor output (frequency shift of SAW oscillator) and the mass loaded on the detector surface. The Brunauer-Emmett-Teller (BET) formula and its improved form are introduced to depict the adsorption behavior of gas on the detector surface. By combining the two methods, we obtain a theoretical model for the response mechanism of SAW gas sensors. By using a commercial SAW gas chromatography (GC) analyzer, an experiment is performed to measure the frequency shifts caused by different concentration of dimethyl methylphosphonate (DMMP). The parameters in the model are given by fitting the experimental results and the theoretical curve agrees well with the experimental data.

  10. Compressive response and deformation mechanisms of vertically aligned helical carbon nanotube forests

    Science.gov (United States)

    Scheffer, V. C.; Thevamaran, R.; Coluci, V. R.

    2018-01-01

    We study the dynamic compressive response of vertically aligned helical carbon nanotube forests using a mesoscale model. To describe the compressive response, the model includes the helical geometry of the constituent coils, the entanglement between neighboring coils, and the sideway interactions among coils. Coarse-grained simulations show forest densification and stress localization, which are caused by different deformation mechanisms such as coil packing, buckling, and crushing. We find that these mechanisms depend on the initial overlap between coils and lead to a nonlinear stress-strain behavior that agrees with recent impact experiments. The nonlinear stress-strain behavior was shown to be composed of an initial linear increase of stress in strain followed by an exponential growth. These regimes are an outcome of the characteristics of both the individual coils and the entangled morphology of the forests.

  11. 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.

  12. Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer

    Science.gov (United States)

    Camps, Jordi; Nguyen, Quang Tri; Padilla-Nash, Hesed M.; Knutsen, Turid; McNeil, Nicole E.; Wangsa, Danny; Hummon, Amanda B.; Grade, Marian; Ried, Thomas; Difilippantonio, Michael J.

    2016-01-01

    To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations. PMID:19691111

  13. 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

  14. Mechanical responses of a-axis GaN nanowires under axial loads

    Science.gov (United States)

    Wang, R. J.; Wang, C. Y.; Feng, Y. T.; Tang, Chun

    2018-03-01

    Gallium nitride (GaN) nanowires (NWs) hold technological significance as functional components in emergent nano-piezotronics. However, the examination of their mechanical responses, especially the mechanistic understanding of behavior beyond elasticity (at failure) remains limited due to the constraints of in situ experimentation. We therefore performed simulations of the molecular dynamics (MD) of the mechanical behavior of [1\\bar{2}10]-oriented GaN NWs subjected to tension or compression loading until failure. The mechanical properties and critical deformation processes are characterized in relation to NW sizes and loading conditions. Detailed examinations revealed that the failure mechanisms are size-dependent and controlled by the dislocation mobility on shuffle-set pyramidal planes. The size dependence of the elastic behavior is also examined in terms of the surface structure determined modification of Young’s modulus. In addition, a comparison with c-axis NWs is made to show how size-effect trends vary with the growth orientation of NWs.

  15. Hypothesis of K+-Recycling Defect Is Not a Primary Deafness Mechanism for Cx26 (GJB2 Deficiency

    Directory of Open Access Journals (Sweden)

    Hong-Bo Zhao

    2017-05-01

    Full Text Available K+-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, GJB2 mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. The hypothesis states that Cx26 deficiency may disrupt inner ear gap junctions and compromise sinking and recycling of expelled K+ ions after hair cell excitation, causing accumulation of K+-ions in the extracellular space around hair cells producing K+-toxicity, which eventually induces hair cell degeneration and hearing loss. However, this hypothesis has never been directly evidenced, even though it has been widely referred to. Recently, more and more experiments demonstrate that this hypothesis may not be a deafness mechanism underlying Cx26 deficiency. In this review article, we summarized recent advances on the K+-recycling and mechanisms underlying Cx26 deficiency induced hearing loss. The mechanisms underlying K+-sinking, which is the first step for K+-recycling in the cochlea, and Cx26 deficiency induced cochlear developmental disorders, which are responsible for Cx26 deficiency induced congenital deafness and associated with disruption of permeability of inner ear gap junctional channels to miRNAs, are also summarized and discussed.

  16. Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

    Science.gov (United States)

    Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

    2015-01-01

    Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

  17. Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli.

    Directory of Open Access Journals (Sweden)

    Brent A Field

    Full Text Available Studies of subjective well-being have conventionally relied upon self-report, which directs subjects' attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure by using functional magnetic resonance imaging (fMRI to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly the activity of brain mechanisms thought to represent hedonic value.

  18. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  19. Modeling of Nonlinear Mechanical Response in CFRP Angle-Ply Laminates

    Science.gov (United States)

    Ogihara, Shinji

    2014-03-01

    It is known that the failure process in angle-ply laminate involves matrix cracking and delamination and that they exhibit nonlinear stress-strain relation. There may be a significant effect of the constituent blocked ply thickness on the mechanical behavior of angle-ply laminates. These days, thin prepregs whose thickness is, for example 50 micron, are developed and commercially available. Therefore, we can design wide variety of laminates with various constituent ply thicknesses. In this study, effects of constituent ply thickness on the nonlinear mechanical behavior and the damage behavior of CFRP angle-ply laminates are investigated experimentally. Based on the experimental results, the mechanical response in CFRP angle-ply laminates is modeled by using the finite strain viscoplasticity model. We evaluated the mechanical behavior and damage behavior in CFRP angle-ply laminates with different constituent ply thickness under tensile loading experimentally. It was found that as the constituent ply thickness decreases, the strength and failure strain increases. We also observed difference in damage behavior. The preliminary results of finite strain viscoplasticity model considering the damage effect for laminated composites are shown. A qualitative agreement is obtained.

  20. 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.

  1. 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.

  2. Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

    Science.gov (United States)

    Yang, Jinfang; Wang, Qian; He, Fenfen; Ding, Yanxia; Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

    2016-01-01

    Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

  3. Physical Mechanisms Responsible for Electrical Conduction in Pt/GaN Schottky Diodes

    Directory of Open Access Journals (Sweden)

    H. MAZARI

    2014-05-01

    Full Text Available 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-semiconductor interface were taken into account.

  4. Novel electro-hydraulic position control system for primary mirror supporting system

    Directory of Open Access Journals (Sweden)

    Xiongbin Peng

    2016-05-01

    Full Text Available In the field of modern large-scale telescope, primary mirror supporting system technology faces the difficulties of theoretically uniform output force request and bias compensation. Therefore, a novel position control system combining hydraulic system with servo motor system is introduced. The novel system ensures uniform output force on supporting points without complicating the mechanical structure. The structures of both primary mirror supporting system and novel position system are described. Then, the mathematical model of novel position control system is derived for controller selection. A proportional–derivative controller is adopted for simulations and experiments of step response and triangle path tracking. The results show that proportional–derivative controller guarantees the system with micrometer-level positioning ability. A modified proportional–derivative controller is utilized to promote system behavior with faster response overshoot. The novel position control system is then applied on primary mirror supporting system. Coupling effect is observed among actuator partitions, and relocation of virtual pivot supporting point is chosen as the decoupling measurement. The position keeping ability of the primary mirror supporting system is verified by rotating the mirror cell at a considerably high rate. The experiment results show that the decoupled system performs better with smaller bias and shorter recovery time.

  5. 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.

  6. 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.

  7. Mechanisms Underlying the Antidepressant Response of Acupuncture via PKA/CREB Signaling Pathway.

    Science.gov (United States)

    Jiang, Huili; Zhang, Xuhui; Wang, Yu; Zhang, Huimin; Li, Jing; Yang, Xinjing; Zhao, Bingcong; Zhang, Chuntao; Yu, Miao; Xu, Mingmin; Yu, Qiuyun; Liang, Xingchen; Li, Xiang; Shi, Peng; Bao, Tuya

    2017-01-01

    Protein kinase A (PKA)/cAMP response element-binding (CREB) protein signaling pathway, contributing to impaired neurogenesis parallel to depressive-like behaviors, has been identified as the crucial factor involved in the antidepressant response of acupuncture. However, the molecular mechanisms associated with antidepressant response of acupuncture, neurogenesis, and depressive-like behaviors ameliorating remain unexplored. The objective was to identify the mechanisms underlying the antidepressant response of acupuncture through PKA signaling pathway in depression rats by employing the PKA signaling pathway inhibitor H89 in in vivo experiments. Our results indicated that the expression of hippocampal PKA- α and p-CREB was significantly downregulated by chronic unpredicted mild stress (CUMS) procedures. Importantly, acupuncture reversed the downregulation of PKA- α and p-CREB. The expression of PKA- α was upregulated by fluoxetine, but not p-CREB. No significant difference was found between Acu and FLX groups on the expression of PKA- α and p-CREB. Interestingly, H89 inhibited the effects of acupuncture or fluoxetine on upregulating the expression of p-CREB, but not PKA- α . There was no significant difference in expression of CREB among the groups. Conclusively, our findings further support the hypothesis that acupuncture could ameliorate depressive-like behaviors by regulating PKA/CREB signaling pathway, which might be mainly mediated by regulating the phosphorylation level of CREB.

  8. Molecular mechanism of radioadaptive response: A cross-adaptive response for enhanced repair of DNA damage in adapted cells

    International Nuclear Information System (INIS)

    Takaji Ikushima

    1997-01-01

    The radioadaptive response (RAR) has been attributed to the induction of a repair mechanism by low doses of ionizing radiation, but the molecular nature of the mechanism is not yet elucidated. We have characterized RAR in a series of experiments in cultured Chinese hamster V79 cells. A 4-h interval is required for the full expression of RAR, which decays with the progression of cell proliferation. Treatments with inhibitors of poly(ADP-ribose) polymerase, protein- or RNA synthesis, and protein kinase C suppress the RAR expression. The RAR cross-reacts on clastogenic lesions induced by other physical and chemical DNA-damaging agents. The presence of newly synthesised proteins has been detected during the expression period. Experiments performed using single-cell gel electrophoresis provided more direct evidence for a faster and enhaced DNA repair rate in adapted cells. Here, using single-cell gel electrophoresis, a cross-adaptive response has been demonstrated for enhanced repair of DNA damage induced by neocarzinostatin in radio-adapted cells. (author)

  9. DNA double-strand break response in stem cells: mechanisms to maintain genomic integrity.

    Science.gov (United States)

    Nagaria, Pratik; Robert, Carine; Rassool, Feyruz V

    2013-02-01

    Embryonic stem cells (ESCs) represent the point of origin of all cells in a given organism and must protect their genomes from both endogenous and exogenous genotoxic stress. DNA double-strand breaks (DSBs) are one of the most lethal forms of damage, and failure to adequately repair DSBs would not only compromise the ability of SCs to self-renew and differentiate, but will also lead to genomic instability and disease. Herein, we describe the mechanisms by which ESCs respond to DSB-inducing agents such as reactive oxygen species (ROS) and ionizing radiation, compared to somatic cells. We will also discuss whether the DSB response is fully reprogrammed in induced pluripotent stem cells (iPSCs) and the role of the DNA damage response (DDR) in the reprogramming of these cells. ESCs have distinct mechanisms to protect themselves against DSBs and oxidative stress compared to somatic cells. The response to damage and stress is crucial for the maintenance of self-renewal and differentiation capacity in SCs. iPSCs appear to reprogram some of the responses to genotoxic stress. However, it remains to be determined if iPSCs also retain some DDR characteristics of the somatic cells of origin. The mechanisms regulating the genomic integrity in ESCs and iPSCs are critical for its safe use in regenerative medicine and may shed light on the pathways and factors that maintain genomic stability, preventing diseases such as cancer. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Stress corrosion mechanisms of alloy-600 polycrystals and monocrystals in primary water: effect of hydrogen

    International Nuclear Information System (INIS)

    Foct, F.

    1999-01-01

    The aim of this study is to identify the mechanisms involved in Alloy 600 primary water stress corrosion cracking. Therefore, this work is mainly focussed on the two following points. The first one is to understand the influence of hydrogen on SCC of industrial Alloy 600 and the second one is to study the crack initiation and propagation on polycrystals and single crystals. A cathodic potential applied during slow strain rate tests does not affect crack initiation but increases the slow crack growth rate by a factor 2 to 5. Cathodic polarisation, cold work and 25 cm 3 STP/kg hydrogen content increase the slow CGR so that the K ISCC (and therefore fast CGR) is reached. The influence of hydrogenated primary water has been studied for the first time on Alloy 600 single crystals. Cracks cannot initiate on tensile specimens but they can propagate on pre-cracked specimens. Transgranular cracks present a precise crystallographic aspect which is similar to that of 316 alloy in MgCl 2 solutions. Moreover, the following results improve the description of the cracking conditions. Firstly, the higher the hydrogen partial pressure, the lower the Alloy 600 passivation current transients. Since this result is not correlated with the effect of hydrogen on SCC, cracking is not caused by a direct effect of dissolved hydrogen on dissolution. Secondly, hydrogen embrittlement of Alloy 600 disappears at temperatures above 200 deg.C. Thirdly, grain boundary sliding (GBS) does not directly act on SCC but shows the mechanical weakness of grain boundaries. Regarding the proposed models for Alloy 600 SCC, it is possible to draw the following conclusions. Internal oxidation or absorbed hydrogen effects are the most probable mechanisms for initiation. Dissolution, internal oxidation and global hydrogen embrittlement models cannot explain crack propagation. On the other hand, the Corrosion Enhanced Plasticity Model gives a good description of the SCC propagation. (author)

  11. Kinetics and mechanism of the selective oxidation of primary aliphatic alcohols under phase transfer catalysis

    Directory of Open Access Journals (Sweden)

    K. Bijudas

    2014-03-01

    Full Text Available Kinetics of the oxidation of primary aliphatic alcohols has been carried out using phase transferred monochromate in benzene. Tetrabutylammonium bromide (TBAB and tetrabutylphosphonium bromide (TBPB are used as phase transfer catalysts (PT catalyst. The reaction shows first order dependence on both [alcohol] and [monochromate ion]. The oxidation leads to the formation of corresponding aldehyde and no traces of carboxylic acid has been detected. The reaction mixture failed to induce the polymerization of added acrylonitrile which rules out the presence radical intermediates in the reaction. Various thermodynamic parameters have been evaluated and a suitable mechanism has been proposed.

  12. Attention Determines Contextual Enhancement versus Suppression in Human Primary Visual Cortex.

    Science.gov (United States)

    Flevaris, Anastasia V; Murray, Scott O

    2015-09-02

    Neural responses in primary visual cortex (V1) depend on stimulus context in seemingly complex ways. For example, responses to an oriented stimulus can be suppressed when it is flanked by iso-oriented versus orthogonally oriented stimuli but can also be enhanced when attention is directed to iso-oriented versus orthogonal flanking stimuli. Thus the exact same contextual stimulus arrangement can have completely opposite effects on neural responses-in some cases leading to orientation-tuned suppression and in other cases leading to orientation-tuned enhancement. Here we show that stimulus-based suppression and enhancement of fMRI responses in humans depends on small changes in the focus of attention and can be explained by a model that combines feature-based attention with response normalization. Neurons in the primary visual cortex (V1) respond to stimuli within a restricted portion of the visual field, termed their "receptive field." However, neuronal responses can also be influenced by stimuli that surround a receptive field, although the nature of these contextual interactions and underlying neural mechanisms are debated. Here we show that the response in V1 to a stimulus in the same context can either be suppressed or enhanced depending on the focus of attention. We are able to explain the results using a simple computational model that combines two well established properties of visual cortical responses: response normalization and feature-based enhancement. Copyright © 2015 the authors 0270-6474/15/3512273-08$15.00/0.

  13. Measuring mechanisms for quality assurance in primary care systems in transition: test of a new instrument in Slovenia and Uzbekistan.

    NARCIS (Netherlands)

    Kringos, D.S.; Boerma, W.G.W.; Pellny, M.

    2009-01-01

    Aim: This WHO study, carried out by the authors, aimed to develop and field test an instrument to assess the availability of structures and mechanisms for managing quality in primary care in countries in transition. Methods: The instrument is based on a literature study, consensus meetings with

  14. An international cross-sectional survey on the Quality and Costs of Primary Care (QUALICO-PC): recruitment and data collection of places delivering primary care across Canada.

    Science.gov (United States)

    Wong, Sabrina T; Chau, Leena W; Hogg, William; Teare, Gary F; Miedema, Baukje; Breton, Mylaine; Aubrey-Bassler, Kris; Katz, Alan; Burge, Fred; Boivin, Antoine; Cooke, Tim; Francoeur, Danièle; Wodchis, Walter P

    2015-02-18

    Performance reporting in primary health care in Canada is challenging because of the dearth of concise and synthesized information. The paucity of information occurs, in part, because the majority of primary health care in Canada is delivered through a multitude of privately owned small businesses with no mechanism or incentives to provide information about their performance. The purpose of this paper is to report the methods used to recruit family physicians and their patients across 10 provinces to provide self-reported information about primary care and how this information could be used in recruitment and data collection for future large scale pan-Canadian and other cross-country studies. Canada participated in an international large scale study-the QUALICO-PC (Quality and Costs of Primary Care) study. A set of four surveys, designed to collect in-depth information regarding primary care activities was collected from: practices, providers, and patients (experiences and values). Invitations (telephone, electronic or mailed) were sent to family physicians. Eligible participants were sent a package of surveys. Provincial teams kept records on the number of: invitation emails/letters sent, physicians who registered, practices that were sent surveys, and practices returning completed surveys. Response and cooperation rates were calculated. Invitations to participate were sent to approximately 23,000 family physicians across Canada. A total of 792 physicians and 8,332 patients from 772 primary care practices completed the surveys, including 1,160 participants completing a Patient Values survey and 7,172 participants completing a Patient Experience survey. Overall, the response rate was very low ranging from 2% (British Columbia) to 21% (Nova Scotia). However, the participation rate was high, ranging from 72% (Ontario) to 100% (New Brunswick/Prince Edward Island and Newfoundland & Labrador). The difficulties obtaining acceptable response rates by family physicians for

  15. 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.

  16. Physico-mechanical properties determination using microscale homotopic measurements: Application to sound and caries-affected primary tooth dentin

    Science.gov (United States)

    Marangos, Orestes; Misra, Anil; Spencer, Paulette; Bohaty, Brenda; Katz, J. Lawrence

    2009-01-01

    Microscale elastic moduli, composition and density have rarely been determined at the same location for biological materials. In this paper, we have performed homotopic measurements to determine the physico-mechanical properties of a second primary molar specimen exhibiting sound and caries-affected regions. A microscale acoustic impedance map of a section through this sample was acquired using scanning acoustic microscopy (SAM). Scanning electron microscopy was then used to obtain mineral mass fraction of the same section using backscattered images. Careful calibration of each method was performed to reduce system effects and obtain accurate data. Resorption, demineralization and hypermineralization mechanisms were considered in order to derive relationships between measured mineral mass fraction and material mass density. As a result, microscale mass density was determined at the same lateral resolution and location as the SAM data. The mass density and the acoustic impedance were combined to find the microscale elastic modulus and study the relationship between microscale composition and mechanical properties. PMID:19059013

  17. Reconstitution of active telomerase in primary human foreskin fibroblasts : effects on proliferative characteristics and response to ionizing radiation

    NARCIS (Netherlands)

    Kampinga, H.H.; Waarde-Verhagen, M.A.W.H. van; Assen-Bolt, A.J. van; Rodemann, H.P.; Prowse, K.R.; Linskens, M.H.K.

    2004-01-01

    Purpose: Telomere shortening has been proposed to trigger senescence, and since most primary cells do not express active telomerase, reactivation of telomerase activity was proposed as a safe and non-transforming way of immortalizing cells. However, to study radiation responses, it is as yet unclear

  18. Biochemical response to ursodeoxycholic acid predicts survival in a North American cohort of primary biliary cirrhosis patients.

    Science.gov (United States)

    Lammert, Craig; Juran, Brian D; Schlicht, Erik; Chan, Landon L; Atkinson, Elizabeth J; de Andrade, Mariza; Lazaridis, Konstantinos N

    2014-10-01

    Biochemical response to ursodeoxycholic acid among patients with primary biliary cirrhosis remains variable, and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with ursodeoxycholic acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Three hundred and ninety-eight PBC patients from the Mayo Clinic PBC Genetic Epidemiology Registry were assessed for ursodeoxycholic acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Three hundred and two (76 %) patients were responders and 96 (24 %) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (hazard ratio (HR) 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR 1.9) and patients with late-stage disease (HR 2.7) after age and sex adjustment. The Toronto criteria are capable of identifying ursodeoxycholic acid-treated primary biliary cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival.

  19. Upregulation of Glucose Uptake and Hexokinase Activity of Primary Human CD4+ T Cells in Response to Infection with HIV-1

    Directory of Open Access Journals (Sweden)

    Maia Kavanagh Williamson

    2018-03-01

    Full Text Available Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1. HIV-1 infected CD4+ T cells showed a marked increase in expression of HK1, as well as the functionally related voltage-dependent anion channel (VDAC protein, but not HK2. The elevation of GLUT, HK1, and VDAC expression in HIV-1 infected cells mirrored replication kinetics and was dependent on virus replication, as evidenced by the use of reverse transcription inhibitors. Finally, we demonstrated that the upregulation of HK1 in HIV-1 infected CD4+ T cells is independent of the viral accessory proteins Vpu, Vif, Nef, and Vpr. Though these data are consistent with HIV-1 dependency on CD4+ T cell glucose metabolism, a cellular response mechanism to infection cannot be ruled out.

  20. A CHROMATIN MODIFYING ENZYME, SDG8, IS REQUIRED FOR MORPHOLOGICAL, GENE EXPRESSION, AND EPIGENETIC RESPONSES TO MECHANICAL STIMULATION

    OpenAIRE

    Christopher Ian Cazzonelli; Nazia eNisar; Andrea C Roberts; Kevin eMurray; Justin O Borevitz; Barry James Pogson

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzy...

  1. A chromatin modifying enzyme, SDG8, is involved in morphological, gene expression, and epigenetic responses to mechanical stimulation

    OpenAIRE

    Cazzonelli, Christopher I.; Nisar, Nazia; Roberts, Andrea C.; Murray, Kevin D.; Borevitz, Justin O.; Pogson, Barry J.

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzym...

  2. MECHANISM OF INTRODUCTION SOCIALLY-RESPONSIBLE MARKETING IN SYSTEM MANAGEMENTS BY TRADE ENTERPRISE

    Directory of Open Access Journals (Sweden)

    Victoria Gladkaya

    2015-12-01

    Full Text Available In the article the mechanism of introduction of the socially-responsible marketing is offered in control system. At his description an author the specific of activity of trade enterprises is taken into account; the best home and foreign works are investigational in the field of the social marketing; the requirement of relatively compatible approach is observed; possibility of further improvement is taken into account, estimations of quality of every stage of mechanism of introduction and on the whole through establishment of key indicators of quality.

  3. 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

  4. IL-23 p19 knockout mice exhibit minimal defects in responses to primary and secondary infection with Francisella tularensis LVS.

    Directory of Open Access Journals (Sweden)

    Sherry L Kurtz

    Full Text Available Our laboratory's investigations into mechanisms of protective immunity against Francisella tularensis Live Vaccine Strain (LVS have uncovered mediators important in host defense against primary infection, as well as those correlated with successful vaccination. One such potential correlate was IL-12p40, a pleiotropic cytokine that promotes Th1 T cell function as part of IL-12p70. LVS-infected IL-12p40 deficient knockout (KO mice maintain a chronic infection, but IL-12p35 KO mice clear LVS infection; thus the role that IL-12p40 plays in immunity to LVS is independent of the IL-12p70 heterodimer. IL-12p40 can also partner with IL-23p19 to create the heterodimeric cytokine IL-23. Here, we directly tested the role of IL-23 in LVS resistance, and found IL-23 to be largely dispensable for immunity to LVS following intradermal or intranasal infection. IL-23p19 KO splenocytes were fully competent in controlling intramacrophage LVS replication in an in vitro overlay assay. Further, antibody responses in IL-23p19 KO mice were similar to those of normal wild type mice after LVS infection. IL-23p19 KO mice or normal wild type mice that survived primary LVS infection survived maximal doses of LVS secondary challenge. Thus p40 has a novel role in clearance of LVS infection that is unrelated to either IL-12 or IL-23.

  5. Oncogene Mimicry as a Mechanism of Primary Resistance to BRAF Inhibitors

    Directory of Open Access Journals (Sweden)

    Martin L. Sos

    2014-08-01

    Full Text Available Despite the development of potent RAF/mitogen-activated protein kinase (MAPK pathway inhibitors, only a fraction of BRAF-mutant patients benefit from treatment with these drugs. Using a combined chemogenomics and chemoproteomics approach, we identify drug-induced RAS-RAF-MEK complex formation in a subset of BRAF-mutant cancer cells characterized by primary resistance to vemurafenib. In these cells, autocrine interleukin-6 (IL-6 secretion may contribute to the primary resistance phenotype via induction of JAK/STAT3 and MAPK signaling. In a subset of cell lines, combined IL-6/MAPK inhibition is able to overcome primary resistance to BRAF-targeted therapy. Overall, we show that the signaling plasticity exerted by primary resistant BRAF-mutant cells is achieved by their ability to mimic signaling features of oncogenic RAS, a strategy that we term “oncogene mimicry.” This model may guide future strategies for overcoming primary resistance observed in these tumors.

  6. Relationships among Sensory Responsiveness, Anxiety, and Ritual Behaviors in Children with and without Atypical Sensory Responsiveness.

    Science.gov (United States)

    Bart, Orit; Bar-Shalita, Tami; Mansour, Hanin; Dar, Reuven

    2017-08-01

    To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. Forty-eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of ≤154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input.

  7. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

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    Qiansheng Huang

    2016-03-01

    Full Text Available Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa were recruited to investigate the effects of di-(2-ethylhexyl phthalate (DEHP at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

  8. A precise form of divisive suppression supports population coding in the primary visual cortex.

    Science.gov (United States)

    MacEvoy, Sean P; Tucker, Thomas R; Fitzpatrick, David

    2009-05-01

    The responses of neurons in the primary visual cortex (V1) to an optimally oriented grating are suppressed when a non-optimal grating is superimposed. Although cross-orientation suppression is thought to reflect mechanisms that maintain a distributed code for orientation, the effect of superimposed gratings on V1 population responses is unknown. Using intrinsic signal optical imaging, we found that patterns of tree shrew V1 activity evoked by superimposed equal-contrast gratings were predicted by the averages of patterns evoked by individual component gratings. This prediction held across contrasts, for summed sinusoidal gratings or nonsumming square-wave gratings, and was evident in single-unit extracellular recordings. Intracellular recordings revealed consistent levels of suppression throughout the time course of subthreshold responses. These results indicate that divisive suppression powerfully governs population responses to multiple orientations. Moreover, the specific form of suppression that we observed appears to support independent population codes for stimulus orientation and strength and calls for a reassessment of mechanisms that underlie cross-orientation suppression.

  9. Anticipation increases tactile stimulus processing in the ipsilateral primary somatosensory cortex.

    Science.gov (United States)

    van Ede, Freek; de Lange, Floris P; Maris, Eric

    2014-10-01

    Stimulus anticipation improves perception. To account for this improvement, we investigated how stimulus processing is altered by anticipation. In contrast to a large body of previous work, we employed a demanding perceptual task and investigated sensory responses that occur beyond early evoked activity in contralateral primary sensory areas: Stimulus-induced modulations of neural oscillations. For this, we recorded magnetoencephalography in 19 humans while they performed a cued tactile identification task involving the identification of either a proximal or a distal stimulation on the fingertips. We varied the cue-target interval between 0 and 1000 ms such that tactile targets occurred at various degrees of anticipation. This allowed us to investigate the influence of anticipation on stimulus processing in a parametric fashion. We observed that anticipation increases the stimulus-induced response (suppression of beta-band oscillations) originating from the ipsilateral primary somatosensory cortex. This occurs in the period in which the tactile memory trace is analyzed and is correlated with the anticipation-induced improvement in tactile perception. We propose that this ipsilateral response indicates distributed processing across bilateral primary sensory cortices, of which the extent increases with anticipation. This constitutes a new and potentially important mechanism contributing to perception and its improvement following anticipation. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Correlating metabolic and anatomic responses of primary lung cancers to radiotherapy by combined F-18 FDG PET-CT imaging

    Directory of Open Access Journals (Sweden)

    Grills Inga

    2007-05-01

    Full Text Available Abstract Background To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy. Methods 36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters was correlated with that of maximum standard uptake value (SUV of the primary lung cancer before and after conventional radiotherapy. Results There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p Conclusion Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.

  11. Mechanisms of radiation-induced conditioned taste aversion learning

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.

    1986-01-01

    The literature on taste aversion learning is reviewed and discussed, with particular emphasis on those studies that have used exposure to ionizing radiation as an unconditioned stimulus to produce a conditioned taste aversion. The primary aim of the review is to attempt to define the mechanisms that lead to the initiation of the taste aversion response following exposure to ionizing radiation. Studies using drug treatments to produce a taste aversion have been included to the extent that they are relevant to understanding the mechanisms by which exposure to ionizing radiation can affect the behavior of the organism. 141 references

  12. A CHROMATIN MODIFYING ENZYME, SDG8, IS REQUIRED FOR MORPHOLOGICAL, GENE EXPRESSION, AND EPIGENETIC RESPONSES TO MECHANICAL STIMULATION

    Directory of Open Access Journals (Sweden)

    Christopher Ian Cazzonelli

    2014-10-01

    Full Text Available Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzyme, SDG8/ASHH2, which can regulate the expression of many touch responsive genes identified in Arabidopsis. SDG8 is required for the permissive expression of touch induced genes; and the loss of function of sdg8 perturbs the maximum levels of induction on selected touch gene targets. SDG8 is required to maintain permissive H3K4 trimethylation marks surrounding the Arabidopsis touch-inducible gene TOUCH 3 (TCH3, which encodes a calmodulin-like protein (CML12. The gene neighbouring was also slightly down regulated, revealing a new target for SDG8 mediated chromatin modification. Finally, sdg8 mutants show perturbed morphological response to wind-agitated mechanical stimuli, implicating an epigenetic memory-forming process in the acclimation response of thigmomorphogenesis.

  13. A chromatin modifying enzyme, SDG8, is involved in morphological, gene expression, and epigenetic responses to mechanical stimulation.

    Science.gov (United States)

    Cazzonelli, Christopher I; Nisar, Nazia; Roberts, Andrea C; Murray, Kevin D; Borevitz, Justin O; Pogson, Barry J

    2014-01-01

    Thigmomorphogenesis is viewed as being a response process of acclimation to short repetitive bursts of mechanical stimulation or touch. The underlying molecular mechanisms that coordinate changes in how touch signals lead to long-term morphological changes are enigmatic. Touch responsive gene expression is rapid and transient, and no transcription factor or DNA regulatory motif has been reported that could confer a genome wide mechanical stimulus. We report here on a chromatin modifying enzyme, SDG8/ASHH2, which can regulate the expression of many touch responsive genes identified in Arabidopsis. SDG8 is required for the permissive expression of touch induced genes; and the loss of function of sdg8 perturbs the maximum levels of induction on selected touch gene targets. SDG8 is required to maintain permissive H3K4 trimethylation marks surrounding the Arabidopsis touch-inducible gene TOUCH 3 (TCH3), which encodes a calmodulin-like protein (CML12). The gene neighboring was also slightly down regulated, revealing a new target for SDG8 mediated chromatin modification. Finally, sdg8 mutants show perturbed morphological response to wind-agitated mechanical stimuli, implicating an epigenetic memory-forming process in the acclimation response of thigmomorphogenesis.

  14. Brain response to primary blast wave using validated finite element models of human head and advanced combat helmet

    Directory of Open Access Journals (Sweden)

    Liying eZhang

    2013-08-01

    Full Text Available Blast-induced traumatic brain injury has emerged as a signature injury in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH, a finite element (FE study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27-0.66 MPa from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP in the head ranged from 0.68-1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10-35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44% was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%. The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence "iso-damage" curves for brain injury are likely different than the Bowen curves

  15. Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

    Directory of Open Access Journals (Sweden)

    Jinfang Yang

    Full Text Available Previous studies have reported inconsistent effects of dietary restriction (DR on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1 of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

  16. Clinical impact of whole body FDG-PET for evaluation of response and therapeutic decision making of primary lymphoma of bone

    International Nuclear Information System (INIS)

    Kim, Sung Eun; Park, Yeon Hee; Cheon, Gi Jeong; Yoo, Ji Young; Ryoo, Baek Yeol; Lee, Seung Sook; Choi, Chang Woon; Lim, Sang Moo

    2004-01-01

    Primary lymphoma of bone (PLB) is one of the rarest primary bone malignancies. The main treatment modality is chemotherapy, which is different from that for other malignant bone tumors. According to the response to primary treatment, subsequent second-line treatment could be different: therefore proper evaluation for treatment effectiveness is needed. However, treatment evaluation is more difficult for bone lesion characteristics than for other lymphomas. It is not easy to determine complete response accurately, and it is difficult to establish subsequent treatment strategies. We investigate the usefulness of the PET scanning in evaluation of PLB, as compared with CT and MRI scanning. A survey of 1.422 NHL patients who had been diagnosed at Korea Cancer Center Hospital between 1989 and 2003 identified 28 patients with PLB (2.0%). Among these cases, FDG-PET had been used for evaluation of diagnosis, response and recurrence in 18 cases. We analyzed and compared conventional CT/MRI findings with FDG-PET scanning findings of these cases. To decide the CR, PET scanning following treatment showed no hypermetabolic lesion with a rapid decline of FDG uptake. However, follow-up CT or MRI showed persistent bone lesion after Partial Response (PR). To decide the early relapse, PET scanning showed definite hypermetabolic lesions with a rapid increase of FDG uptake. However, follow-up CT or MRI showed no specific changes. We found that PET scanning is a useful method in treatment evaluation for PBL. FDG-PET will provide major contribution to decide further management in PBL

  17. Dynamic Mechanical Compression of Chondrocytes for Tissue Engineering: A Critical Review

    Directory of Open Access Journals (Sweden)

    Devon E. Anderson

    2017-12-01

    Full Text Available Articular cartilage functions to transmit and translate loads. In a classical structure–function relationship, the tissue resides in a dynamic mechanical environment that drives the formation of a highly organized tissue architecture suited to its biomechanical role. The dynamic mechanical environment includes multiaxial compressive and shear strains as well as hydrostatic and osmotic pressures. As the mechanical environment is known to modulate cell fate and influence tissue development toward a defined architecture in situ, dynamic mechanical loading has been hypothesized to induce the structure–function relationship during attempts at in vitro regeneration of articular cartilage. Researchers have designed increasingly sophisticated bioreactors with dynamic mechanical regimes, but the response of chondrocytes to dynamic compression and shear loading remains poorly characterized due to wide variation in study design, system variables, and outcome measurements. We assessed the literature pertaining to the use of dynamic compressive bioreactors for in vitro generation of cartilaginous tissue from primary and expanded chondrocytes. We used specific search terms to identify relevant publications from the PubMed database and manually sorted the data. It was very challenging to find consensus between studies because of species, age, cell source, and culture differences, coupled with the many loading regimes and the types of analyses used. Early studies that evaluated the response of primary bovine chondrocytes within hydrogels, and that employed dynamic single-axis compression with physiologic loading parameters, reported consistently favorable responses at the tissue level, with upregulation of biochemical synthesis and biomechanical properties. However, they rarely assessed the cellular response with gene expression or mechanotransduction pathway analyses. Later studies that employed increasingly sophisticated biomaterial-based systems, cells

  18. Dynamic Mechanical Compression of Chondrocytes for Tissue Engineering: A Critical Review.

    Science.gov (United States)

    Anderson, Devon E; Johnstone, Brian

    2017-01-01

    Articular cartilage functions to transmit and translate loads. In a classical structure-function relationship, the tissue resides in a dynamic mechanical environment that drives the formation of a highly organized tissue architecture suited to its biomechanical role. The dynamic mechanical environment includes multiaxial compressive and shear strains as well as hydrostatic and osmotic pressures. As the mechanical environment is known to modulate cell fate and influence tissue development toward a defined architecture in situ , dynamic mechanical loading has been hypothesized to induce the structure-function relationship during attempts at in vitro regeneration of articular cartilage. Researchers have designed increasingly sophisticated bioreactors with dynamic mechanical regimes, but the response of chondrocytes to dynamic compression and shear loading remains poorly characterized due to wide variation in study design, system variables, and outcome measurements. We assessed the literature pertaining to the use of dynamic compressive bioreactors for in vitro generation of cartilaginous tissue from primary and expanded chondrocytes. We used specific search terms to identify relevant publications from the PubMed database and manually sorted the data. It was very challenging to find consensus between studies because of species, age, cell source, and culture differences, coupled with the many loading regimes and the types of analyses used. Early studies that evaluated the response of primary bovine chondrocytes within hydrogels, and that employed dynamic single-axis compression with physiologic loading parameters, reported consistently favorable responses at the tissue level, with upregulation of biochemical synthesis and biomechanical properties. However, they rarely assessed the cellular response with gene expression or mechanotransduction pathway analyses. Later studies that employed increasingly sophisticated biomaterial-based systems, cells derived from different

  19. Systems of mechanized and reactive droplets powered by multi-responsive surfactants

    Science.gov (United States)

    Yang, Zhijie; Wei, Jingjing; Sobolev, Yaroslav I.; Grzybowski, Bartosz A.

    2018-01-01

    Although ‘active’ surfactants, which are responsive to individual external stimuli such as temperature, electric or magnetic fields, light, redox processes or chemical agents, are well known, it would be interesting to combine several of these properties within one surfactant species. Such multi-responsive surfactants could provide ways of manipulating individual droplets and possibly assembling them into larger systems of dynamic reactors. Here we describe surfactants based on functionalized nanoparticle dimers that combine all of these and several other characteristics. These surfactants and therefore the droplets that they cover are simultaneously addressable by magnetic, optical and electric fields. As a result, the surfactant-covered droplets can be assembled into various hierarchical structures, including dynamic ones, in which light powers the rapid rotation of the droplets. Such rotating droplets can transfer mechanical torques to their non-nearest neighbours, thus acting like systems of mechanical gears. Furthermore, droplets of different types can be merged by applying electric fields and, owing to interfacial jamming, can form complex, non-spherical, ‘patchy’ structures with different surface regions covered with different surfactants. In systems of droplets that carry different chemicals, combinations of multiple stimuli can be used to control the orientations of the droplets, inter-droplet transport, mixing of contents and, ultimately, sequences of chemical reactions. Overall, the multi-responsive active surfactants that we describe provide an unprecedented level of flexibility with which liquid droplets can be manipulated, assembled and reacted.

  20. MnTM-4-PyP modulates endogenous antioxidant responses and protects primary cortical neurons against oxidative stress.

    Science.gov (United States)

    Cheng, Kuo-Yuan; Guo, Fei; Lu, Jia-Qi; Cao, Yuan-Zhao; Wang, Tian-Chang; Yang, Qi; Xia, Qing

    2015-05-01

    Oxidative stress is a direct cause of injury in various neural diseases. Manganese porphyrins (MnPs), a large category of superoxide dismutase (SOD) mimics, shown universally to have effects in numerous neural disease models in vivo. Given their complex intracellular redox activities, detailed mechanisms underlying the biomedical efficacies are not fully elucidated. This study sought to investigate the regulation of endogenous antioxidant systems by a MnP (MnTM-4-PyP) and its role in the protection against neural oxidative stress. Primary cortical neurons were treated with MnTM-4-PyP prior to hydrogen peroxide-induced oxidative stress. MnTM-4-PyP increased cell viability, reduced intracellular level of reactive oxygen species, inhibited mitochondrial apoptotic pathway, and ameliorated endoplasmic reticulum function. The protein levels and activities of endogenous SODs were elevated, but not those of catalase. SOD2 transcription was promoted in a transcription factor-specific manner. Additionally, we found FOXO3A and Sirt3 levels also increased. These effects were not observed with MnTM-4-PyP alone. Induction of various levels of endogenous antioxidant responses by MnTM-4-PyP has indispensable functions in its protection for cortical neurons against hydrogen peroxide-induced oxidative stress. © 2014 John Wiley & Sons Ltd.

  1. Possible roles of transglutaminases in molecular mechanisms responsible for human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Nicola Gaetano Gatta

    2016-11-01

    Full Text Available Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted/crosslinked adducts or –OH groups (to form ester linkages. In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s Disease, Parkinson’s Disease, supranuclear palsy, Huntington’s Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review describes the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.

  2. 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.

  3. 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.

  4. Primary School Teachers' Perceptions of Adequacy and Quality of Physical Facilities in Public Primary Schools under Free Primary Education

    Science.gov (United States)

    Muthima, Ndirangu Wahome; Udoto, Maurice O.; Anditi, Zephania O.

    2016-01-01

    The Free Primary Education (FPE) programme was commissioned in Kenya in January 2003 to provide basic education to all children of school going age and to ease the burden of cost sharing from the parents. However, even though the public primary school class teachers were to shoulder the greatest responsibility in the implementation of this…

  5. Role of IL-12 and IFN-γ in immune response to toxoplasma gondii infection

    International Nuclear Information System (INIS)

    Moawad, M.A.F.; ElGawish, M.A.M.

    2004-01-01

    Interlenkin 12 (IL-12) is a potent immunoregulatory molecule that is critically involved in a wide range of diseases. In several murine models of intracellular infection, endogenous IL-12 has been shown to be crucial for the generation of a protective Th1 response in a primary infection for a intracellular pathogens. Interferon-gamma (IFN-γ) is also an important mediator of cellular immunity against microbial pathogens and tumor cells due to its potent capacity to activate macrophages for enhanced cytotoxicity. The aim of the present study is to evaluate the immune response to toxoplasma gondii after primary inflection (infected groups and secondary infection (re-infected groups for over 19 weeks (the time of the experiment). the evaluation was assessed by measurements of levels of IL-12 and IFN-γ using ELISA technique in the sera of these infected rats. The results demonstrated that the primary immune response induced a fluctuation in the levels of IL-12 in the sera of infected rats, which reached maximum value of 122.6 ±1.4 pg/ml after 15 weeks of primary infection. While, in the challenged groups (secondary immune response, re-infected groups) the levels of IL-12 were generally lower than that of the primary immune response. On the other hand, IFN-γ levels increased significantly in the secondary immune response (re-infected groups) as compared to primary immune response 9 infected groups) In conclusion, the results suggest that IL-12 might have a role in the defense mechanism against intracellular infection with T-gondii especially in primary immune response than in the secondary immune response. This is in contrast to IFN-γ that takes the up-hand in secondary immune response to T-gondii infection

  6. Pupil size directly modulates the feedforward response in human primary visual cortex independently of attention.

    Science.gov (United States)

    Bombeke, Klaas; Duthoo, Wout; Mueller, Sven C; Hopf, Jens-Max; Boehler, C Nico

    2016-02-15

    Controversy revolves around the question of whether psychological factors like attention and emotion can influence the initial feedforward response in primary visual cortex (V1). Although traditionally, the electrophysiological correlate of this response in humans (the C1 component) has been found to be unaltered by psychological influences, a number of recent studies have described attentional and emotional modulations. Yet, research into psychological effects on the feedforward V1 response has neglected possible direct contributions of concomitant pupil-size modulations, which are known to also occur under various conditions of attentional load and emotional state. Here we tested the hypothesis that such pupil-size differences themselves directly affect the feedforward V1 response. We report data from two complementary experiments, in which we used procedures that modulate pupil size without differences in attentional load or emotion while simultaneously recording pupil-size and EEG data. Our results confirm that pupil size indeed directly influences the feedforward V1 response, showing an inverse relationship between pupil size and early V1 activity. While it is unclear in how far this effect represents a functionally-relevant adaptation, it identifies pupil-size differences as an important modulating factor of the feedforward response of V1 and could hence represent a confounding variable in research investigating the neural influence of psychological factors on early visual processing. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. A prospective study of shoulder pain in primary care: Prevalence of imaged pathology and response to guided diagnostic blocks

    Directory of Open Access Journals (Sweden)

    McNair Peter J

    2011-05-01

    Full Text Available Abstract Background The prevalence of imaged pathology in primary care has received little attention and the relevance of identified pathology to symptoms remains unclear. This paper reports the prevalence of imaged pathology and the association between pathology and response to diagnostic blocks into the subacromial bursa (SAB, acromioclavicular joint (ACJ and glenohumeral joint (GHJ. Methods Consecutive patients with shoulder pain recruited from primary care underwent standardised x-ray, diagnostic ultrasound scan and diagnostic injections of local anaesthetic into the SAB and ACJ. Subjects who reported less than 80% reduction in pain following either of these injections were referred for a magnetic resonance arthrogram (MRA and GHJ diagnostic block. Differences in proportions of positive and negative imaging findings in the anaesthetic response groups were assessed using Fishers test and odds ratios were calculated a for positive anaesthetic response (PAR to diagnostic blocks. Results In the 208 subjects recruited, the rotator cuff and SAB displayed the highest prevalence of pathology on both ultrasound (50% and 31% respectively and MRA (65% and 76% respectively. The prevalence of PAR following SAB injection was 34% and ACJ injection 14%. Of the 59% reporting a negative anaesthetic response (NAR for both of these injections, 16% demonstrated a PAR to GHJ injection. A full thickness tear of supraspinatus on ultrasound was associated with PAR to SAB injection (OR 5.02; p p p p ≤ 0.05. Conclusions Rotator cuff and SAB pathology were the most common findings on ultrasound and MRA. Evidence of a full thickness supraspinatus tear was associated with symptoms arising from the subacromial region, and a biceps tendon sheath effusion and an intact rotator cuff were associated with an intra-articular GHJ pain source. When combined with clinical information, these results may help guide diagnostic decision making in primary care.

  8. 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.

  9. 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).

  10. Role of hydrogen in the intergranular cracking mechanism by stress corrosion in primary medium of nickel based alloys 600 and 690

    International Nuclear Information System (INIS)

    Odemer, G.; Coudurier, A.; Jambon, F.; Chene, J.; Odemer, G.; Coudurier, A.; Chene, J.

    2007-01-01

    The aim of this work is to characterize the sensitivity to hydrogen embrittlement of alloys 600 and 690 in order to better understand the eventual role of hydrogen in the stress corrosion mechanism which affects these alloys when they are exposed in PWR primary medium. (O.M.)

  11. Electro-Mechanical Response and Engineering Properties of Piezocomposite with Imperfect Interface

    Directory of Open Access Journals (Sweden)

    Tippayaphalapholgul Rattanan

    2016-01-01

    Full Text Available Composites of piezoelectric materials are widely use in practical applications such as nondestructive testing devices, smart adaptive structures and medical devices. A thorough understanding of coupled electro-elastic response and properties of piezocomposite are crucial for the development and design of piezoelectric composite materials used in advanced applications. The micromechanics analysis is employed in this paper to determine the response and engineering properties of the piezocomposite. A mechanical imperfect interface bonding between piezoelectric inclusion and polymer matrix is taken into consideration in the analysis. The micromechanics analysis is based on the Boundary Element Method (BEM together with the periodic micro-field micromechanics theory. A selected set of numerical results is presented to investigate the influence of volume ratio and interface bonding condition on effective piezocomposite material coefficients and portray basic features of coupled electroelastic response within the domain of piezocomposite unit cell.

  12. Predicting meaningful outcomes to medication and self-help treatments for binge-eating disorder in primary care: The significance of early rapid response.

    Science.gov (United States)

    Grilo, Carlos M; White, Marney A; Masheb, Robin M; Gueorguieva, Ralitza

    2015-04-01

    We examined rapid response among obese patients with binge-eating disorder (BED) in a randomized clinical trial testing antiobesity medication and self-help cognitive-behavioral therapy (shCBT), alone and in combination, in primary-care settings. One hundred four obese patients with BED were randomly assigned to 1 of 4 treatments: sibutramine, placebo, shCBT + sibutramine, or shCBT + placebo. Treatments were delivered by generalist primary-care physicians and the medications were given double-blind. Independent assessments were performed by trained and monitored doctoral research clinicians monthly throughout treatment, posttreatment (4 months), and at 6- and 12-month follow-ups (i.e., 16 months after randomization). Rapid response, defined as ≥65% reduction in binge eating by the fourth treatment week, was used to predict outcomes. Rapid response characterized 47% of patients, was unrelated to demographic and baseline clinical characteristics, and was significantly associated, prospectively, with remission from binge eating at posttreatment (51% vs. 9% for nonrapid responders), 6-month (53% vs. 23.6%), and 12-month (46.9% vs. 23.6%) follow-ups. Mixed-effects model analyses revealed that rapid response was significantly associated with greater decreases in binge-eating or eating-disorder psychopathology, depression, and percent weight loss. Our findings, based on a diverse obese patient group receiving medication and shCBT for BED in primary-care settings, indicate that patients who have a rapid response achieve good clinical outcomes through 12-month follow-ups after ending treatment. Rapid response represents a strong prognostic indicator of clinically meaningful outcomes, even in low-intensity medication and self-help interventions. Rapid response has important clinical implications for stepped-care treatment models for BED. clinicaltrials.gov: NCT00537810 (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  13. Psychometric analysis of the Generalized Anxiety Disorder scale (GAD-7) in primary care using modern item response theory.

    Science.gov (United States)

    Jordan, Pascal; Shedden-Mora, Meike C; Löwe, Bernd

    2017-01-01

    The Generalized Anxiety Disorder scale (GAD-7) is one of the most frequently used diagnostic self-report scales for screening, diagnosis and severity assessment of anxiety disorder. Its psychometric properties from the view of the Item Response Theory paradigm have rarely been investigated. We aimed to close this gap by analyzing the GAD-7 within a large sample of primary care patients with respect to its psychometric properties and its implications for scoring using Item Response Theory. Robust, nonparametric statistics were used to check unidimensionality of the GAD-7. A graded response model was fitted using a Bayesian approach. The model fit was evaluated using posterior predictive p-values, item information functions were derived and optimal predictions of anxiety were calculated. The sample included N = 3404 primary care patients (60% female; mean age, 52,2; standard deviation 19.2) The analysis indicated no deviations of the GAD-7 scale from unidimensionality and a decent fit of a graded response model. The commonly suggested ultra-brief measure consisting of the first two items, the GAD-2, was supported by item information analysis. The first four items discriminated better than the last three items with respect to latent anxiety. The information provided by the first four items should be weighted more heavily. Moreover, estimates corresponding to low to moderate levels of anxiety show greater variability. The psychometric validity of the GAD-2 was supported by our analysis.

  14. Suppression of the primary immune response in rainbow trout, Salmo gairdneri, sublethally exposed to tritiated water during embryogenesis

    International Nuclear Information System (INIS)

    Strand, J.A.

    1975-01-01

    Antibody synthesis in response to vaccination with a 0.1 cc (1.8 x 10 8 cells/cc) intraperitoneally injected heat-killed strain of Flexibacter columnaris was employed to investigate the effect of tritium irradiation (0, 0.04, 0.4, 4.0 and 40.0 rads total dose for 20 days during embryogenesis) on development of the primary immune response in 5-month rainbow trout, Salmo gairdneri. Total serum protein measurements and electrophoretic separation of blood serum proteins followed by densitometric analyses were performed to assess the potential for qualitative and quantitative changes in blood serum components which conceivably accounted for suppressed immune responsiveness in tritium-irradiated fish. Data on the biological effects of tritium on early life stages in terms of hatchability, abnormality, latent mortality, and growth were also collected. A review of all experiments directed at determining the effects of early radiation exposure on the parameters of hatchability, incidence of abnormality, latent mortality and depressed growth, revealed considerable variation among similar treatments and indicated that significant effects at dose levels of 50 rads and below were not consistently demonstrated. While present experimental results demonstrated that the primary immune response in juvenile rainbow trout was significantly suppressed following embryonic exposure to tritium at essentially the 1.0 μCi/ml level, and perhaps at the 0.1 μCi/ml level, these concentrations are no less than 5 to 6 orders of magnitude above present levels for tritium in the aquatic environment

  15. DPOAE generation dependence on primary frequencies ratio

    Science.gov (United States)

    Botti, Teresa; Sisto, Renata; Moleti, Arturo; D'Amato, Luisa; Sanjust, Filippo

    2015-12-01

    Two different mechanisms are responsible for the DPOAE generation. The nonlinear distortion wave-fixed mechanism generates the DPOAE Zero-Latency (ZL) component, as a backward traveling wave from the "overlap" region. Linear reflection of the forward DP wave (IDP) generates the DPOAE Long-Latency (LL) component through a place-fixed mechanism. ZL and LL components add up vectorially to generate the DPOAE recorded in the ear canal. The 2f1 - f2 and 2f2 - f1 DPOAE intensity depends on the stimulus level and on the primary frequency ratio r = f2/f1, where f1 and f2 are the primary stimuli frequencies. Here we study the behavior of the ZL and LL DPOAE components as a function of r by both numerical and laboratory experiments, measuring DPAOEs with an equal primary levels (L1 = L2) paradigm in the range [35, 75] dB SPL, with r ranging in [1.1, 1.45]. Numerical simulations of a nonlocal nonlinear model have been performed without cochlear roughness, to suppress the linear reflection mechanism. In this way the model solution at the base represents the DPOAE ZL component, and the solution at the corresponding DPOAE tonotopic place corresponds to the IDP. This technique has been not effectual to study the 2f2 - f1 DPOAE, as a consequence of its generation mechanism. While the 2f1 - f2 generation place is known to be the tonotopic place x(f2), the 2f2 - f1 DPOAE one has to be assumed basal to its corresponding reflection place. That is because ZL components generated in x(f2) cannot significantly pass through their resonant place. Moreover increasing the ratio r, 2f2 - f1 ZL and LL generation place approach each other, because the overlap region of primary tones decreases. Consequently, the distinction between the two places becomes complicated. DPOAEs have been measured in six young normal-hearing subjects. DPOAE ZL and LL components have been separated by a time-frequency filtering method based on the wavelet transform 1. due to their different phase gradient delay

  16. A neural mechanism of dynamic gating of task-relevant information by top-down influence in primary visual cortex.

    Science.gov (United States)

    Kamiyama, Akikazu; Fujita, Kazuhisa; Kashimori, Yoshiki

    2016-12-01

    Visual recognition involves bidirectional information flow, which consists of bottom-up information coding from retina and top-down information coding from higher visual areas. Recent studies have demonstrated the involvement of early visual areas such as primary visual area (V1) in recognition and memory formation. V1 neurons are not passive transformers of sensory inputs but work as adaptive processor, changing their function according to behavioral context. Top-down signals affect tuning property of V1 neurons and contribute to the gating of sensory information relevant to behavior. However, little is known about the neuronal mechanism underlying the gating of task-relevant information in V1. To address this issue, we focus on task-dependent tuning modulations of V1 neurons in two tasks of perceptual learning. We develop a model of the V1, which receives feedforward input from lateral geniculate nucleus and top-down input from a higher visual area. We show here that the change in a balance between excitation and inhibition in V1 connectivity is necessary for gating task-relevant information in V1. The balance change well accounts for the modulations of tuning characteristic and temporal properties of V1 neuronal responses. We also show that the balance change of V1 connectivity is shaped by top-down signals with temporal correlations reflecting the perceptual strategies of the two tasks. We propose a learning mechanism by which synaptic balance is modulated. To conclude, top-down signal changes the synaptic balance between excitation and inhibition in V1 connectivity, enabling early visual area such as V1 to gate context-dependent information under multiple task performances. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Disturbed hypoxic responses as a pathogenic mechanism of diabetic foot ulcers.

    Science.gov (United States)

    Catrina, Sergiu-Bogdan; Zheng, Xiaowei

    2016-01-01

    Diabetic foot ulceration (DFU) is a chronic complication of diabetes that is characterized by impaired wound healing in the lower extremities. DFU remains a major clinical challenge because of poor understanding of its pathogenic mechanisms. Impaired wound healing in diabetes is characterized by decreased angiogenesis, reduced bone marrow-derived endothelial progenitor cell (EPC) recruitment, and decreased fibroblast and keratinocyte proliferation and migration. Recently, increasing evidence has suggested that increased hypoxic conditions and impaired cellular responses to hypoxia are essential pathogenic factors of delayed wound healing in DFU. Hypoxia-inducible factor-1 (HIF-1, a heterodimer of HIF-1α and HIF-1β) is a master regulator of oxygen homeostasis that mediates the adaptive cellular responses to hypoxia by regulating the expression of genes involved in angiogenesis, metabolic changes, proliferation, migration, and cell survival. However, HIF-1 signalling is inhibited in diabetes as a result of hyperglycaemia-induced HIF-1α destabilization and functional repression. Increasing HIF-1α expression and activity using various approaches promotes angiogenesis, EPC recruitment, and granulation, thereby improving wound healing in experimental diabetes. The mechanisms underlying HIF-1α regulation in diabetes and the therapeutic strategies targeting HIF-1 signalling for the treatment of diabetic wounds are discussed in this review. Further investigations of the pathways involved in HIF-1α regulation in diabetes are required to advance our understanding of the mechanisms underlying impaired wound healing in diabetes and to provide a foundation for developing novel therapeutic approaches to treat DFU. Copyright © 2016 John Wiley & Sons, Ltd.

  18. 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.

  19. 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

  20. A Supply Chain Coordination Mechanism with Cost Sharing of Corporate Social Responsibility

    Directory of Open Access Journals (Sweden)

    Yong Liu

    2018-04-01

    Full Text Available The competition of modern enterprises has shifted from brand competition among enterprises of the past to that of supply chains; and considering corporate social responsibility (CSR within supply chain management has become an inevitable requirement for improving the competitiveness of enterprises and conforms to the trend of standardization of social responsibility guidelines. This paper deals with channel coordination and decision-making in a CSR supply chain that is comprised of a dominant retailer and n homogeneous suppliers. The Stackelberg game is employed to analyze the optimal decision-making of this supply chain under either decentralized or centralized decision-making processes. After that, the thought and method of super conflict equilibrium are used to design the coordination decision-making mechanism of this supply chain based on the cost sharing of CSR to solve channel conflict and to optimize the decision. The results show that the proposed mechanism based on the cost sharing of CSR is better than those with only either the retailer or the suppliers being CSR; and it can well describe the relationship between the retailer and the suppliers, and increase the eagerness of the retailer and suppliers to carry out their CSR under various circumstances without having the profits adversely affected. As a matter of fact, this mechanism maximizes the profits of the entire supply chain system and also enhances the competitiveness of the chain.

  1. Esophageal Large-Cell Neuroendocrine Carcinoma with Inconsistent Response to Treatment in the Primary and Metastatic Lesions

    Directory of Open Access Journals (Sweden)

    Takashi Tomiyama

    2018-05-01

    Full Text Available Esophageal large-cell neuroendocrine carcinoma (NEC is a rare malignant tumor that is characterized by high-grade malignancy and a poor prognosis. However, the rarity of esophageal NEC has prevented the development of an established treatment, and no reports have described a discrepancy in the effectiveness of cisplatin plus irinotecan between primary and metastatic lesions. A 43-year-old Japanese man was referred to our hospital with refractory epigastralgia. A previous gastrointestinal endoscopy had revealed a 50-mm type 2 tumor in the abdominal esophagus. The pathological findings indicated poorly differentiated squamous cell carcinoma. Contrast-enhanced computed tomography revealed a metastatic liver tumor. One cycle of fluorouracil and cisplatin was not effective, and endoscopy was repeatedly performed. The pathological findings indicated a large-cell malignant tumor with tumor cells that were positive for CD56, synaptophysin, and Ki-67 (> 80%. Based on a diagnosis of esophageal large-cell NEC with a metastatic liver tumor, the patient received cisplatin plus irinotecan biweekly. After 4 months, computed tomography revealed marked shrinkage of the metastatic tumor, but the patient complained of dysphagia. Endoscopy revealed enlargement of the primary tumor, which was then treated using radiotherapy plus fluorouracil and cisplatin. The primary tumor subsequently shrank, and the patient’s symptoms were relieved, but the metastatic tumor grew. Thus, chemoradiotherapy could be an option for managing a primary esophageal large-cell NEC that does not respond to chemotherapy alone. However, the possibility of an inconsistent response to therapy in primary and metastatic lesions should be considered.

  2. Permanence of suppression of the primary immune response in rainbow trout, Salmo gairdneri, sublethally exposed to tritiated water during embryognesis

    International Nuclear Information System (INIS)

    Strand, J.A.; Fujihara, M.P.; Poston, T.M.; Abernethy, C.S.

    1982-01-01

    Previous experiments demonstrated that antibody synthesis in response to a challenge from the bacterium, Flexibacter columnaris, was significantly suppressed in juvenile (5 month) rainbow trout following exposure to tritium at doses as low as 4.0 rads when administered during the first 20 days of embryogenesis. In continuing studies, a secondary challenge to columnaris cells delivered to yearling (17 month) trout was used to test the hypothesis that early embryonic exposure to tritium irradiation (0, 0.04, 0.4, 4.0, and 40.0 rads) resulted in permanent injury to the primary immune process. Results indicated that under the prescribed experimental conditions, suppression of the primary immune response was permanent; that is, the degree of injury in yearling fish (17 months) equaled or exceeded that found in juvenile fish (5 months). At levels in the range of the maximum permissible concentration (MPC), tritium produced measurable, dose dependent, and irreversible suppression of immune capacity in affected fish. The threshold-free and exponential nature of the dose-response curve suggests extrapolation of effects to even lower exposures. (author)

  3. Food and Natural Materials Target Mechanisms to Effectively Regulate Allergic Responses.

    Science.gov (United States)

    Shin, Hee Soon; Shon, Dong-Hwa

    2015-01-01

    An immune hypersensitivity disorder called allergy is caused by diverse allergens entering the body via skin contact, injection, ingestion, and/or inhalation. These allergic responses may develop into allergic disorders, including inflammations such as atopic dermatitis, asthma, anaphylaxis, food allergies, and allergic rhinitis. Several drugs have been developed to treat these allergic disorders; however, long-term intake of these drugs could have adverse effects. As an alternative to these medicines, food and natural materials that ameliorate allergic disorder symptoms without producing any side effects can be consumed. Food and natural materials can effectively regulate successive allergic responses in an allergic chain-reaction mechanism in the following ways: [1] Inhibition of allergen permeation via paracellular diffusion into epithelial cells, [2] suppression of type 2 T-helper (Th) cell-related cytokine production by regulating Th1/Th2 balance, [3] inhibition of pathogenic effector CD4(+) T cell differentiation by inducing regulatory T cells (Treg), and [4] inhibition of degranulation in mast cells. The immunomodulatory effects of food and natural materials on each target mechanism were scientifically verified and shown to alleviate allergic disorder symptoms. Furthermore, consumption of certain food and natural materials such as fenugreek, skullcap, chitin/chitosan, and cheonggukjang as anti-allergics have merits such as safety (no adverse side effects), multiple suppressive effects (as a mixture would contain various components that are active against allergic responses), and ease of consumption when required. These merits and anti-allergic properties of food and natural materials help control various allergic disorders.

  4. Chemokines and antimicrobial peptides have a cag-dependent early response to Helicobacter pylori infection in primary human gastric epithelial cells.

    Science.gov (United States)

    Mustapha, Pascale; Paris, Isabelle; Garcia, Magali; Tran, Cong Tri; Cremniter, Julie; Garnier, Martine; Faure, Jean-Pierre; Barthes, Thierry; Boneca, Ivo G; Morel, Franck; Lecron, Jean-Claude; Burucoa, Christophe; Bodet, Charles

    2014-07-01

    Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  5. Transport coefficients and mechanical response in hard-disk colloidal suspensions

    International Nuclear Information System (INIS)

    Zhang Bo-Kai; Ma Yu-Qiang; Li Jian; Chen Kang; Tian Wen-De

    2016-01-01

    We investigate the transport properties and mechanical response of glassy hard disks using nonlinear Langevin equation theory. We derive expressions for the elastic shear modulus and viscosity in two dimensions on the basis of thermal-activated barrier-hopping dynamics and mechanically accelerated motion. Dense hard disks exhibit phenomena such as softening elasticity, shear-thinning of viscosity, and yielding upon deformation, which are qualitatively similar to dense hard-sphere colloidal suspensions in three dimensions. These phenomena can be ascribed to stress-induced “landscape tilting”. Quantitative comparisons of these phenomena between hard disks and hard spheres are presented. Interestingly, we find that the density dependence of yield stress in hard disks is much more significant than in hard spheres. Our work provides a foundation for further generalizing the nonlinear Langevin equation theory to address slow dynamics and rheological behavior in binary or polydisperse mixtures of hard or soft disks. (rapid communication)

  6. 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.

  7. 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.

  8. Mechanical Adaptability of the MMP-Responsive Film Improves the Functionality of Endothelial Cell Monolayer.

    Science.gov (United States)

    Hu, Mi; Chang, Hao; Zhang, He; Wang, Jing; Lei, Wen-Xi; Li, Bo-Chao; Ren, Ke-Feng; Ji, Jian

    2017-07-01

    Extracellular matrix and cells are inherent in coordinating and adapting to each other during all physiological and pathological processes. Synthetic materials, however, show rarely reciprocal and spatiotemporal responses to cells, and lacking self-adapting properties as well. Here, a mechanical adaptability based on the matrix metalloproteinase (MMPs) sensitive polyelectrolyte film is reported. Poly-lysine (PLL) and methacrylated hyaluronic acid (HA-MA) nanolayers are employed to build the thin film through the layer-by-layer assembly, and it is further crosslinked using MMP sensitive peptides, which endows the films with changeable mechanical properties in response to MMPs. It is demonstrated that stiffness of the (PLL/HA-MA) films increases with the crosslinking, and then decreases in response to a treatment of enzyme. Consequently, the crosslinked (PLL/HA-MA) films reveal effective growth of endothelial cells (ECs), leading to fast formation of EC monolayer. Importantly, significantly improved endothelial function of the EC monolayer, which is characterized by integrity, biomolecules release, expression of function related gene, and antithrombotic properties, is achieved along with the decrosslinking of the film because of EC-secreted MMPs. These results suggest that mechanical adaptability of substrate in Young's modulus plays a significant role in endothelial progression, which shows great application potential in tissue engineering, regenerative medicine, and organ-on-a-chip. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Attention modulates the responses of simple cells in monkey primary visual cortex.

    Science.gov (United States)

    McAdams, Carrie J; Reid, R Clay

    2005-11-23

    Spatial attention has long been postulated to act as a spotlight that increases the salience of visual stimuli at the attended location. We examined the effects of attention on the receptive fields of simple cells in primary visual cortex (V1) by training macaque monkeys to perform a task with two modes. In the attended mode, the stimuli relevant to the animal's task overlay the receptive field of the neuron being recorded. In the unattended mode, the animal was cued to attend to stimuli outside the receptive field of that neuron. The relevant stimulus, a colored pixel, was briefly presented within a white-noise stimulus, a flickering grid of black and white pixels. The receptive fields of the neurons were mapped by correlating spikes with the white-noise stimulus in both attended and unattended modes. We found that attention could cause significant modulation of the visually evoked response despite an absence of significant effects on the overall firing rates. On further examination of the relationship between the strength of the visual stimulation and the firing rate, we found that attention appears to cause multiplicative scaling of the visually evoked responses of simple cells, demonstrating that attention reaches back to the initial stages of visual cortical processing.

  10. 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.

  11. 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

  12. On the effects of geometry, defects, and material asymmetry on the mechanical response of shape memory alloy cellular lattice structures

    International Nuclear Information System (INIS)

    Ravari, M R Karamooz; Kadkhodaei, M; Ghaei, A; Esfahani, S Nasr; Andani, M Taheri; Elahinia, M; Karaca, H

    2016-01-01

    Shape memory alloy (such as NiTi) cellular lattice structures are a new class of advanced materials with many potential applications. The cost of fabrication of these structures however is high. It is therefore necessary to develop modeling methods to predict the functional behavior of these alloys before fabrication. The main aim of the present study is to assess the effects of geometry, microstructural imperfections and material asymmetric response of dense shape memory alloys on the mechanical response of cellular structures. To this end, several cellular and dense NiTi samples are fabricated using a selective laser melting process. Both cellular and dense specimens were tested in compression in order to obtain their stress–strain response. For modeling purposes, a three -dimensional (3D) constitutive model based on microplane theory which is able to describe the material asymmetry was employed. Five finite element models based on unit cell and multi-cell methods were generated to predict the mechanical response of cellular lattices. The results show the considerable effects of the microstructural imperfections on the mechanical response of the cellular lattice structures. The asymmetric material response of the bulk material also affects the mechanical response of the corresponding cellular structure. (paper)

  13. Innate immune responses induced by lipopolysaccharide and lipoteichoic acid in primary goat mammary epithelial cells.

    Science.gov (United States)

    Bulgari, Omar; Dong, Xianwen; Roca, Alfred L; Caroli, Anna M; Loor, Juan J

    2017-01-01

    Innate immune responses induced by in vitro stimulation of primary mammary epithelial cells (MEC) using Gram-negative lipopolysaccharide (LPS) and Gram-positive lipoteichoic acid (LTA) bacterial cell wall components are well- characterized in bovine species. The objective of the current study was to characterize the downstream regulation of the inflammatory response induced by Toll-like receptors in primary goat MEC (pgMEC). We performed quantitative real-time RT-PCR (qPCR) to measure mRNA levels of 9 genes involved in transcriptional regulation or antibacterial activity: Toll-like receptor 2 ( TLR2 ), Toll-like receptor 4 ( TLR4 ), prostaglandin-endoperoxide synthase 2 ( PTGS2 ), interferon induced protein with tetratricopeptide repeats 3 ( IFIT3 ), interferon regulatory factor 3 ( IRF3 ), myeloid differentiation primary response 88 ( MYD88 ), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 ( NFKB1 ), Toll interacting protein ( TOLLIP ), and lactoferrin ( LTF ). Furthermore, we analyzed 7 cytokines involved in Toll-like receptor signaling pathways: C-C motif chemokine ligand 2 ( CCL2 ), C-C motif chemokine ligand 5 ( CCL5 ), C-X-C motif chemokine ligand 6 ( CXCL6 ), interleukin 8 ( CXCL8 ), interleukin 1 beta ( IL1B ), interleukin 6 ( IL6 ), and tumor necrosis factor alpha ( TNF ). Stimulation of pgMEC with LPS for 3 h led to an increase in expression of CCL2 , CXCL6 , IL6 , CXCL8 , PTGS2 , IFIT3 , MYD88 , NFKB1 , and TLR4 ( P  < 0.05). Except for IL6 , and PTGS2 , the same genes had greater expression than controls at 6 h post-LPS ( P  < 0.05). Expression of CCL5 , PTGS2 , IFIT3 , NFKB1 , TLR4 , and TOLLIP was greater than controls after 3 h of incubation with LTA ( P  < 0.05). Compared to controls, stimulation with LTA for 6 h led to greater expression of PTGS2 , IFIT3 , NFKB1 , and TOLLIP ( P  < 0.05) whereas the expression of CXCL6 , CXCL8 , and TLR4 was lower ( P  < 0.05). At 3 h incubation with both toxins

  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. Responsiveness of Lebanon's primary healthcare centers to non-communicable diseases and related healthcare needs.

    Science.gov (United States)

    Yassoub, Rami; Hashimi, Suha; Awada, Siham; El-Jardali, Fadi

    2014-01-01

    Lebanon currently faces a rise in non-communicable diseases (NCD) that is stressing the population's health and financial well-being. Preventive care is recognized as the optimal health equitable, cost-effective solution. The study aims to assess the responsiveness of primary health care centers (PHCs) to NCD, and identify the needed health arrangements and responsibilities of PHCs, the Ministry Of Public Health and other healthcare system entities, for PHCs to purse a more preventive role against NCD. Single and group interviews were conducted via a semi-structured questionnaire with 10 PHCs from Lebanon's primary health care network that have undergone recent pilot accreditation and are recognized for having quality services and facilities. This manifested administrative aspects and NCD-related services of PHCs and generated information regarding the centers' deficiencies, strengths and areas needing improvement for fulfilling a more preventive role. Administrative features of PHCs varied according to number and type of health personnel employed. Variations and deficiencies within and among PHCs were manifested specifically at the level of cardiovascular and respiratory diseases and cancer. PHCs identified the pilot accreditation as beneficial at the administrative and clinical levels; however, various financial and non-financial resources, in addition to establishing a strong referral system with secondary care settings and further arrangements with MOPH, are necessary for PHCs to pursue a stronger preventive role. The generated results denote needed changes within the healthcare system's governance, financing and delivery. They involve empowering PHCs and increasing their breadth of services, allocating a greater portion of national budget to health and preventive care, and equipping PHCs with personnel skilled in conducting community-wide preventive activities. Copyright © 2013 John Wiley & Sons, Ltd.

  16. 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.

  17. 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.

  18. Detection of stimulus deviance within primate primary auditory cortex: intracortical mechanisms of mismatch negativity (MMN) generation.

    Science.gov (United States)

    Javitt, D C; Steinschneider, M; Schroeder, C E; Vaughan, H G; Arezzo, J C

    1994-12-26

    Mismatch negativity (MMN) is a cognitive, auditory event-related potential (AEP) that reflects preattentive detection of stimulus deviance and indexes the operation of the auditory sensory ('echoic') memory system. MMN is elicited most commonly in an auditory oddball paradigm in which a sequence of repetitive standard stimuli is interrupted infrequently and unexpectedly by a physically deviant 'oddball' stimulus. Electro- and magnetoencephalographic dipole mapping studies have localized the generators of MMN to supratemporal auditory cortex in the vicinity of Heschl's gyrus, but have not determined the degree to which MMN reflects activation within primary auditory cortex (AI) itself. The present study, using moveable multichannel electrodes inserted acutely into superior temporal plane, demonstrates a significant contribution of AI to scalp-recorded MMN in the monkey, as reflected by greater response of AI to loud or soft clicks presented as deviants than to the same stimuli presented as repetitive standards. The MMN-like activity was localized primarily to supragranular laminae within AI. Thus, standard and deviant stimuli elicited similar degrees of initial, thalamocortical excitation. In contrast, responses within supragranular cortex were significantly larger to deviant stimuli than to standards. No MMN-like activity was detected in a limited number to passes that penetrated anterior and medial to AI. AI plays a well established role in the decoding of the acoustic properties of individual stimuli. The present study demonstrates that primary auditory cortex also plays an important role in processing the relationships between stimuli, and thus participates in cognitive, as well as purely sensory, processing of auditory information.

  19. Common and distinct neural mechanisms of attentional switching and response conflict.

    Science.gov (United States)

    Kim, Chobok; Johnson, Nathan F; Gold, Brian T

    2012-08-21

    The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 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.

  1. Acute hemodynamic response to vasodilators in primary pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Kulkarni H

    1996-01-01

    Full Text Available Acute hemodynamic effects of high flow oxygen (O2 inhalation, sublingual isosorbide dinitrate (ISDN, intravenous aminophylline (AMN and sublingual nifedipine (NIF were studied in 32 patients with primary pulmonary hypertension (PPH. In 30 out of 32 patients the basal ratio of pulmonary to systemic vascular resistance (Rp/Rs was > 0.5 (mean = 0.77 +/- 0.20. Oxygen caused significant decrease in the mean resistance ratio to 0.68 +/- 0.20 (p = 0.005. ISDN, AMN and NIF caused increase in the resistance ratio to 0.79 +/- 0.26; 0.78 +/- 0.26; and 0.80 +/- 0.23 respectively. O2, ISDN, AMN and NIF caused a fall of Rp/Rs in 21 (65.6%, 10 (31.2%, 10(31.2% and 9(28.1% patients respectively. Thus, of the four drugs tested high flow O2 inhalation resulted in fall of Rp/Rs in two thirds of patients whereas ISDN, AMN and NIF caused a mean rise in Rp/Rs. One third of patients did respond acutely to the latter three drugs. Acute hemodynamic studies are useful before prescribing vasodilators in patients with PPH since more of the commonly used drugs like ISDN, AMN, NIF could have detrimental hemodynamic responses in some patients. However, great caution should be exercised before performing hemodynamic study as the procedure has definite mortality and morbidity.

  2. Response of the primary piping loop to an HCDA

    International Nuclear Information System (INIS)

    Chang, Y.W.; Moneim, M.T.A.; Wang, C.Y.; Gvildys, J.

    1975-01-01

    The paper describes a method for analyzing the response of the primary piping loop that consists of straight pipes, elbows, and other components connected in series and subject to hypothetical core disruptive accident (HCDA) loads at both ends of the loop. The complete hydrodynamic equations in two-dimensions, that include both the nonlinear convective and viscous dissipation terms are used for the fluid dynamics together with the implicit ICE technique. The external walls of the pipes and components are treated as thin shells in which the analysis accounts for the membrane and bending strength of the wall, elastic-plastic material behavior, as well as large deformation under the effect of transient loading conditions. In the straight pipes, the flow is assumed to be axisymmetric; in the elbow regions, the two dimensions considered are the r and theta directions. The flow in the other components is also assumed to be axisymmetric; the components are modeled as a circular cylinder, in which the radius of the cylinder can be varied to conform with the outside shape of the component and the flow area inside can be changed independently from the outside shape. However, they must remain axially symmetric. The method is applied to a piping loop which consists of six elastic-plastic pipes and five rigid elbows connected in series and subjected to pressure pulses at both ends of the loop

  3. Acute and regressive scleroderma concomitant to an acute CMV primary infection.

    Science.gov (United States)

    Goulabchand, Radjiv; Khellaf, Lakhdar; Forestier, Amandine; Costes, Valerie; Foulongne, Vincent; le Quellec, Alain; Guilpain, Philippe

    2014-12-01

    To describe the pathophysiological mechanisms involving cytomegalovirus (CMV) primary infection and natural killer (NK) cell expansion in the development of localized scleroderma. A 43-year-old woman presented acute erythematous discoloration and skin thickening concerning face, neck, trunk, abdomen, and the four limbs, predominantly in proximal areas. Our case did not respond to systemic sclerosis criteria diagnosis. However, skin and muscle biopsy revealed early scleroderma associated with capillary thrombi, and tissue infiltration with NK cells (CD56+/Granzyme B). Scleroderma was attributed to CMV primary infection responsible for cytolytic hepatitis (7-fold over the limit) and circulating NK cell excess. After 6 months of prednisone and a 2-year follow-up, a complete resolution of symptoms was observed. Our observation suggests a potential triggering role of CMV primary infection in the development of scleroderma. Histological features from our observation addresses the role of CMV and NK cells in the development of endothelial damage and fibrotic process. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. A Good IDS Response Protocol of MANET Containment Strategies

    Science.gov (United States)

    Cheng, Bo-Chao; Chen, Huan; Tseng, Ryh-Yuh

    Much recent research concentrates on designing an Intrusion Detection System (IDS) to detect the misbehaviors of the malicious node in MANET with ad-hoc and mobility natures. However, without rapid and appropriate IDS response mechanisms performing follow-up management services, even the best IDS cannot achieve the desired primary goal of the incident response. A competent containment strategy is needed to limit the extent of an attack in the Incident Response Life Cycle. Inspired by the T-cell mechanisms in the human immune system, we propose an efficient MANET IDS response protocol (T-SecAODV) that can rapidly and accurately disseminate alerts of the malicious node attacks to other nodes so as to modify their AODV routing tables to isolate the malicious nodes. Simulations are conducted by the network simulator (Qualnet), and the experiment results indicate that T-SecAODV is able to spread alerts steadily while greatly reduce faulty rumors under simultaneous multiple malicious node attacks.

  5. [Association between anxiety and coping strategies employed by primary caregivers of bedridden patients].

    Science.gov (United States)

    Cedillo-Torres, Arianna Gabriela; Grijalva, María Guadalupe; Santaella-Hidalgo, Guadalupe B; Cuevas-Abad, Martha; González Pedraza-Avilés, Alberto

    2015-01-01

    The primary caregiver faces a set of problems derived from the responsibility to provide care to his patient; this leads to the creation of complex psychological responses that act as a mechanism known as cognitive and behavioral coping. The objective was to determine if there was a correlation between the level of anxiety and the coping strategies used by primary caregivers of bedridden patients. Transversal, descriptive and correlational study. Beck Anxiety Inventory and the Coping Strategies Inventory were used. We used Spearman's rank correlation coefficient, a significance level of 0.05 and the statistical program SPSS, version 15. We included 60 primary caregivers. The most common score for anxiety was moderate (28 %). The most frequently used strategy was problem solving (average = 14.7). By relating the level of anxiety and coping strategies a significant correlation was obtained with problem solving: r = 0.260; self-criticism, r = 0.425; wishful thinking, r = 0.412; and social withdrawal, r = 0.453. The anxiety has an impact on the way caregivers cope; most of the population who have moderate to severe anxiety use desadaptive strategies focused on emotion.

  6. In vivo patch-clamp analysis of response properties of rat primary somatosensory cortical neurons responding to noxious stimulation of the facial skin

    Directory of Open Access Journals (Sweden)

    Nasu Masanori

    2010-05-01

    Full Text Available Abstract Background Although it has been widely accepted that the primary somatosensory (SI cortex plays an important role in pain perception, it still remains unclear how the nociceptive mechanisms of synaptic transmission occur at the single neuron level. The aim of the present study was to examine whether noxious stimulation applied to the orofacial area evokes the synaptic response of SI neurons in urethane-anesthetized rats using an in vivo patch-clamp technique. Results In vivo whole-cell current-clamp recordings were performed in rat SI neurons (layers III-IV. Twenty-seven out of 63 neurons were identified in the mechanical receptive field of the orofacial area (36 neurons showed no receptive field and they were classified as non-nociceptive (low-threshold mechanoreceptive; 6/27, 22% and nociceptive neurons. Nociceptive neurons were further divided into wide-dynamic range neurons (3/27, 11% and nociceptive-specific neurons (18/27, 67%. In the majority of these neurons, a proportion of the excitatory postsynaptic potentials (EPSPs reached the threshold, and then generated random discharges of action potentials. Noxious mechanical stimuli applied to the receptive field elicited a discharge of action potentials on the barrage of EPSPs. In the case of noxious chemical stimulation applied as mustard oil to the orofacial area, the membrane potential shifted depolarization and the rate of spontaneous discharges gradually increased as did the noxious pinch-evoked discharge rates, which were usually associated with potentiated EPSP amplitudes. Conclusions The present study provides evidence that SI neurons in deep layers III-V respond to the temporal summation of EPSPs due to noxious mechanical and chemical stimulation applied to the orofacial area and that these neurons may contribute to the processing of nociceptive information, including hyperalgesia.

  7. Acknowledging and allocating responsibility for clinical inertia in the management of Type 2 diabetes in primary care: a qualitative study.

    Science.gov (United States)

    Zafar, A; Stone, M A; Davies, M J; Khunti, K

    2015-03-01

    Failure to intensify treatment in patients with Type 2 diabetes with suboptimal blood glucose control has been termed clinical inertia and has been shown to contribute to poorer patient outcomes. We aimed to identify and explore perceptions about clinical inertia from the perspective of primary healthcare providers. A qualitative study was conducted in Leicestershire and Northamptonshire, UK. Purposive sampling was based on healthcare providers working in primary care settings with 'higher' and 'lower' target achievement based on routine data. Twenty semi-structured interviews were conducted, face-to-face or by telephone. Thematic analysis was informed by the constant comparative approach. An important broad theme that emerged during the analysis was related to attribution and explanation of responsibility for clinical inertia. This included general willingness to accept a degree of responsibility for clinical inertia. In some cases, however, participants had inaccurate perceptions about levels of target achievement in their primary care centres, as indicated by routine data. Participants sought to lessen their own sense of accountability by highlighting patient-level barriers such as comorbidities and human fallibility, and also system-level barriers, particularly time constraints. Perceptions about ways of addressing the problem of clinical inertia were not seen as straightforward, further emphasizing a complex and cumulative pattern of barriers. In order to understand and address the problem of clinical inertia, provider, patient- and system-level barriers should be considered together rather than as separate issues. Acknowledgement of responsibility should be regarded positively as a motivator for change. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  8. 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

  9. N-P Co-Limitation of Primary Production and Response of Arthropods to N and P in Early Primary Succession on Mount St. Helens Volcano

    Science.gov (United States)

    Bishop, John G.; O'Hara, Niamh B.; Titus, Jonathan H.; Apple, Jennifer L.; Gill, Richard A.; Wynn, Louise

    2010-01-01

    Background The effect of low nutrient availability on plant-consumer interactions during early succession is poorly understood. The low productivity and complexity of primary successional communities are expected to limit diversity and abundance of arthropods, but few studies have examined arthropod responses to enhanced nutrient supply in this context. We investigated the effects of nitrogen (N) and phosphorus (P) addition on plant productivity and arthropod abundance on 24-yr-old soils at Mount St. Helens volcano. Methodology/Principal Findings We measured the relative abundance of eight arthropod orders and five families in plots that received N, P, or no nutrients for 3–5 years. We also measured plant % cover, leaf %N, and plant diversity. Vegetation responded rapidly to N addition but showed a lagged response to P that, combined with evidence of increased N fixation, suggested P-limitation to N availability. After 3 yrs of fertilization, orthopterans (primarily Anabrus simplex (Tettigoniidae) and Melanoplus spp (Acrididae)) showed a striking attraction to P addition plots, while no other taxa responded to fertilization. After 5 yrs of fertilization, orthopteran density in the same plots increased 80%–130% with P addition and 40% with N. Using structural equation modeling, we show that in year 3 orthopteran abundance was associated with a P-mediated increase in plant cover (or correlated increases in resource quality), whereas in year 5 orthopteran density was not related to cover, diversity or plant %N, but rather to unmeasured effects of P, such as its influence on other aspects of resource quality. Conclusions/Significance The marked surprising response to P by orthopterans, combined with a previous observation of P-limitation in lepidopteran herbivores at these sites, suggests that P-mediated effects of food quantity or quality are critical to insect herbivores in this N-P co-limited primary successional system. Our results also support a previous

  10. Housing maintenance of primary cooling pump I of Kartini reactor

    International Nuclear Information System (INIS)

    Agung Nugroho; Wahyu Imam W

    2013-01-01

    Housing maintenance of Primary Cooling Pump have been done with purpose to enhance capability of fluid block and stopping leakage. The procedures of modification are follow: Replace mechanical seal type Nock 560 – 1 ½'' by mechanical seal type Nock 560 - 38, modification gland plate/housing with to lathe the diameter of gland plate/housing from diameter of 54 mm to 60 mm, in size setting-up mechanical seal, alignment and then function test. The result of the modification are: mechanical seal has been installed, housing has been modified, and the leakage of primary cooling water has been repaired and operated properly. Conclusion of the maintenance are the primary cooling water pump is working well, because the primary cooling water is not leakage any more. (author)

  11. Effect of fuel assembly mechanical design changes on dynamic response of reactor pressure vessel system under extreme loadings

    International Nuclear Information System (INIS)

    Bhandari, D.R.; Hankinson, M.F.

    1993-01-01

    This paper presents the results of a study to assess the effect of fuel assembly mechanical design changes on the dynamic response of a pressurized water reactor vessel and reactor internals under Loss-Of-Coolant Accident (LOCA) conditions. The results of this study show that the dynamic response of the reactor vessel internals and the core under extreme loadings, such as LOCA, is very sensitive to fuel assembly mechanical design changes. (author)

  12. Marginal Micro-leakage of Self-etch and All-in One Adhesives to Primary Teeth, with Mechanical or Chemo-Mechanical Caries Removal

    Directory of Open Access Journals (Sweden)

    Nouzari A

    2016-06-01

    Full Text Available Statement of Problem: Chemo-mechanical caries removal is an effective alternative to the traditional rotary drilling method. One of the factors that can influence micro-leakage is the method of caries removal. Objectives: To compare the micro-leakage of resin composite in primary dentition using self-etch and all-in one adhesives following conventional and chemo-mechanical caries removal. Materials and Methods: Sixty extracted human primary anterior teeth with class III carious lesions were collected. The selected teeth were divided randomly into two groups each consisting of 30 teeth. In group1 carious lesions were removed using Carisolv multi mix gel. In group 2, caries was removed using round steel burs in a slow–speed hand piece. Then, the specimens in each group were randomly divided into two subgroups (A and B of 15 and treated by either Clearfil SE Bond (CSEB or Scotch bond. All prepared cavities were filled with a resin composite (Estellite. All the specimens were stored in distilled water at 37ºC for 24 hours and then thermocycled in 5ºC and 55ºC water with a dwell time of 20 seconds for 1500 cycles. The specimens were immersed in 1% methylene blue solution for 24 hours, removed, washed and sectioned mesiodistally. The sectioned splits were examined under a stereomicroscope to determine the micro-leakage scores. The data were analyzed using Kruskal-Wallis Test in SPSS version 21. Results: There were no significant differences between micro-leakage scores among the four groups (p = 0.127. Score 0 of micro-leakage was detected for 60% of the specimens in group 1-A (Carisolv + CSEB, 73% of the group 2-A (hand piece + CSEB, 80% of the group 1-B (Carisolv + Scotch bond, and 93% of the group 2-B in which caries was removed using hand piece and bonded with Scotch bond . Conclusions: Although caries removal using hand piece bur along with using Scotch bond adhesive performed less micro-leakage, it would seems that the use of Carisolv

  13. An EPID response calculation algorithm using spatial beam characteristics of primary, head scattered and MLC transmitted radiation

    International Nuclear Information System (INIS)

    Rosca, Florin; Zygmanski, Piotr

    2008-01-01

    We have developed an independent algorithm for the prediction of electronic portal imaging device (EPID) response. The algorithm uses a set of images [open beam, closed multileaf collimator (MLC), various fence and modified sweeping gap patterns] to separately characterize the primary and head-scatter contributions to EPID response. It also characterizes the relevant dosimetric properties of the MLC: Transmission, dosimetric gap, MLC scatter [P. Zygmansky et al., J. Appl. Clin. Med. Phys. 8(4) (2007)], inter-leaf leakage, and tongue and groove [F. Lorenz et al., Phys. Med. Biol. 52, 5985-5999 (2007)]. The primary radiation is modeled with a single Gaussian distribution defined at the target position, while the head-scatter radiation is modeled with a triple Gaussian distribution defined downstream of the target. The distances between the target and the head-scatter source, jaws, and MLC are model parameters. The scatter associated with the EPID is implicit in the model. Open beam images are predicted to within 1% of the maximum value across the image. Other MLC test patterns and intensity-modulated radiation therapy fluences are predicted to within 1.5% of the maximum value. The presented method was applied to the Varian aS500 EPID but is designed to work with any planar detector with sufficient spatial resolution

  14. 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

  15. 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.

  16. The Kyoto mechanisms and technological innovation

    International Nuclear Information System (INIS)

    Lund, Henrik

    2006-01-01

    Climate change response, including the implementation of the Kyoto targets as the first step, calls for technological innovation of future sustainable energy systems. Based on the Danish case, this paper evaluates the type of technological change necessary. During a period of 30 years, Denmark managed to stabilize primary energy supply, and CO 2 emissions decreased by 10%, during a period of 20 years. However, after the introduction of the Kyoto Mechanisms, Denmark has changed its strategy. Instead of continuing the domestic CO 2 emission controls, Denmark plans to buy CO 2 reductions in other countries. Consequently, the innovative technological development has changed. This paper evaluates the character of such change and makes preliminary recommendations for policies to encourage the use of the Kyoto Mechanisms as an acceleration of the necessary technological innovation. (author)

  17. Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

    Science.gov (United States)

    Xu, Yuan; Dai, Feng

    2018-03-01

    A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

  18. Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

    Directory of Open Access Journals (Sweden)

    Mary Anna Carbone

    Full Text Available The statistical power of genome-wide association (GWA studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG. Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR upon overexpression of transgenic human glaucoma-associated myocilin (MYOC. We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

  19. Genes of the unfolded protein response pathway harbor risk alleles for primary open angle glaucoma.

    Science.gov (United States)

    Carbone, Mary Anna; Chen, Yuhong; Hughes, Guy A; Weinreb, Robert N; Zabriskie, Norman A; Zhang, Kang; Anholt, Robert R H

    2011-01-01

    The statistical power of genome-wide association (GWA) studies to detect risk alleles for human diseases is limited by the unfavorable ratio of SNPs to study subjects. This multiple testing problem can be surmounted with very large population sizes when common alleles of large effects give rise to disease status. However, GWA approaches fall short when many rare alleles may give rise to a common disease, or when the number of subjects that can be recruited is limited. Here, we demonstrate that this multiple testing problem can be overcome by a comparative genomics approach in which an initial genome-wide screen in a genetically amenable model organism is used to identify human orthologues that may harbor risk alleles for adult-onset primary open angle glaucoma (POAG). Glaucoma is a major cause of blindness, which affects over 60 million people worldwide. Several genes have been associated with juvenile onset glaucoma, but genetic factors that predispose to adult onset primary open angle glaucoma (POAG) remain largely unknown. Previous genome-wide analysis in a Drosophila ocular hypertension model identified transcripts with altered regulation and showed induction of the unfolded protein response (UPR) upon overexpression of transgenic human glaucoma-associated myocilin (MYOC). We selected 16 orthologous genes with 62 polymorphic markers and identified in two independent human populations two genes of the UPR that harbor POAG risk alleles, BIRC6 and PDIA5. Thus, effectiveness of the UPR in response to accumulation of misfolded or aggregated proteins may contribute to the pathogenesis of POAG and provide targets for early therapeutic intervention.

  20. Resources, attitudes and culture: an understanding of the factors that influence the functioning of accountability mechanisms in primary health care settings.

    Science.gov (United States)

    Cleary, Susan M; Molyneux, Sassy; Gilson, Lucy

    2013-08-16

    District level health system governance is recognised as an important but challenging element of health system development in low and middle-income countries. Accountability is a more recent focus in health system debates. Accountability mechanisms are governance tools that seek to regulate answerability between the health system and the community (external accountability) and/or between different levels of the health system (bureaucratic accountability). External accountability has attracted significant attention in recent years, but bureaucratic accountability mechanisms, and the interactions between the two forms of accountability, have been relatively neglected. This is an important gap given that webs of accountability relationships exist within every health system. There is a need to strike a balance between achieving accountability upwards within the health system (for example through information reporting arrangements) while at the same time allowing for the local level innovation that could improve quality of care and patient responsiveness. Using a descriptive literature review, this paper examines the factors that influence the functioning of accountability mechanisms and relationships within the district health system, and draws out the implications for responsiveness to patients and communities. We also seek to understand the practices that might strengthen accountability in ways that improve responsiveness--of the health system to citizens' needs and rights, and of providers to patients. The review highlights the ways in which bureaucratic accountability mechanisms often constrain the functioning of external accountability mechanisms. For example, meeting the expectations of relatively powerful managers further up the system may crowd out efforts to respond to citizens and patients. Organisational cultures characterized by supervision and management systems focused on compliance to centrally defined outputs and targets can constrain front line

  1. 42 CFR 411.22 - Reimbursement obligations of primary payers and entities that received payment from primary payers.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Reimbursement obligations of primary payers and... Provisions § 411.22 Reimbursement obligations of primary payers and entities that received payment from... reimburse CMS for any payment if it is demonstrated that the primary payer has or had a responsibility to...

  2. Optical-response properties in an atom-assisted optomechanical system with a mechanical pump

    Science.gov (United States)

    Sun, Xue-Jian; Chen, Hao; Liu, Wen-Xiao; Li, Hong-Rong

    2017-05-01

    We investigate the optical-response properties of a coherent-mechanical pumped optomechanical system (OMS) coupled to a Λ-type three-level atomic ensemble. Due to the optomechanical and the cavity-atom couplings, the optomechanically induced transparency (OMIT) and electromagnetically induced transparency (EIT) phenomena could both be observed from our proposal. In the presence of a coherent mechanical pump, we show that the OMIT behavior of the probe field exhibits a phase-dependent effect, leading to the switch from OMIT to optomechanically induced absorption or amplification, while the feature of EIT remains unchanged. The distinctly different effects of the mechanical pump on OMIT and EIT behavior assure us that the absorption (amplification) and transparency of the output probe field can be simultaneously observed. Moreover, a tunable switch from slow to fast light can also be realized by tuning the phase and amplitude of the mechanical pump. In particular, the presence of the atomic ensemble can further adjust the group delay, providing additional flexibility for achieving the tunable switch.

  3. Mechanisms of resistance to decitabine in the myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Taichun Qin

    Full Text Available The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC is approved for the treatment of myelodysplastic syndromes (MDS, but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS.We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance. We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM analysis of global methylation in secondary resistance.Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05, suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P<.05. On average, the methylation of 10 genes was lower at relapse (16.1% compared to diagnosis (18.1% (P<.05. MCAM analysis showed decreased methylation of an average of 4.5% (range 0.6%-9.7% of the genes at relapse. By contrast, new cytogenetic changes were found in 20% of patients.Pharmacological mechanisms are involved in primary resistance to DAC, whereas hypomethylation does not prevent a relapse for patients with DAC treatment.

  4. Shock vibration and damage responses of primary auxiliary buildings from aircraft impact

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sang Shup [Korea Atomic Energy Research Institute, 1045 Daeduk-daero, Dukjin-dong, Yuseong-gu, Daejeon 305-303 (Korea, Republic of); Department of Civil and Environmental Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of); Hahm, Daegi [Korea Atomic Energy Research Institute, 1045 Daeduk-daero, Dukjin-dong, Yuseong-gu, Daejeon 305-303 (Korea, Republic of); Park, Taehyo, E-mail: cepark@hanyang.ac.kr [Department of Civil and Environmental Engineering, Hanyang University, Seoul 133-791 (Korea, Republic of)

    2016-12-15

    Highlights: • Aircraft impact analyses of PABs were performed using both the force-time history method and missile-target interaction method. • The jet fuel was considered by using the added mass modeling method and SPH method, respectively. • The FRS and the structural integrity of the external wall of the PABs against an aircraft impact were analyzed. - Abstract: Safety assessments on nuclear power plants (NPPs) subjected to an aircraft impact (AI) caused by terrorists are pivotal focuses for amelioration of present. To date, most studies have mainly focused on structure responses and the integrity of the containment building at a nuclear island (NI) subjected to AI. However, the safety assessment of internal equipment and components by shock vibration as well as the structure damage induced by AI are also important. In this study, aircraft impact analyses (AIA) of primary auxiliary buildings (PABs) were carried out using both the force–time history method and the missile–target interaction method. For the AIA, the jet fuel was taken into account by using the added mass modeling method and the smooth particles hydrodynamics (SPH) method, respectively. In addition, the floor response spectra (FRS) and the structural integrity of the external wall of the PAB against an AI were analyzed. Finally, the difference in the FRS at the location of the components on both sides of the bay was analyzed.

  5. Thermal and Mechanical Buckling and Postbuckling Responses of Selected Curved Composite Panels

    Science.gov (United States)

    Breivik, Nicole L.; Hyer, Michael W.; Starnes, James H., Jr.

    1998-01-01

    The results of an experimental and numerical study of the buckling and postbuckling responses of selected unstiffened curved composite panels subjected to mechanical end shortening and a uniform temperature increase are presented. The uniform temperature increase induces thermal stresses in the panel when the axial displacement is constrained. An apparatus for testing curved panels at elevated temperature is described, numerical results generated by using a geometrically nonlinear finite element analysis code are presented. Several analytical modeling refinements that provide more accurate representation of the actual experimental conditions, and the relative contribution of each refinement, are discussed. Experimental results and numerical predictions are presented and compared for three loading conditions including mechanical end shortening alone, heating the panels to 250 F followed by mechanical end shortening, and heating the panels to 400 F. Changes in the coefficients of thermal expansion were observed as temperature was increased above 330 F. The effects of these changes on the experimental results are discussed for temperatures up to 400 F.

  6. Dynamical mechanisms for sensitive response of aperiodic firing cells to external stimulation

    International Nuclear Information System (INIS)

    Xie Yong; Xu Jianxue; Hu Sanjue; Kang Yanmei; Yang Hongjun; Duan Yubin

    2004-01-01

    An interesting phenomenon that aperiodic firing neurons have a higher sensitivity to drugs than periodic firing neurons have been reported for the chronically compressed dorsal root ganglion neurons in rats. In this study, the dynamical mechanisms for such a phenomenon are uncovered from the viewpoint of dynamical systems theory. We use the Rose-Hindmarsh neuron model to illustrate our opinions. Periodic orbit theory is introduced to characterize the dynamical behavior of aperiodic firing neurons. It is considered that bifurcations, crises and sensitive dependence of chaotic motions on control parameters can be the underlying mechanisms. And then, a similar analysis is applied to the modified Chay model describing the firing behavior of pancreatic beta cells. The same dynamical mechanisms can be obtained underlying that aperiodic firing cells are more sensitive to external stimulation than periodic firing ones. As a result, we conjecture that sensitive response of aperiodic firing cells to external stimulation is a universal property of excitable cells

  7. Failure by void coalescence in metallic materials containing primary and secondary voids subject to intense shearing

    DEFF Research Database (Denmark)

    Nielsen, Kim Lau; Tvergaard, Viggo

    2011-01-01

    Failure under intense shearing at close to zero stress triaxiality is widely observed for ductile metallic materials, and is identified in experiments as smeared-out dimples on the fracture surface. Numerical cell-model studies of equal sized voids have revealed that the mechanism governing...... this shear failure mode boils down to the interaction between primary voids which rotate and elongate until coalescence occurs under severe plastic deformation of the internal ligaments. The objective of this paper is to analyze this failure mechanism of primary voids and to study the effect of smaller...... secondary damage that co-exists with or nucleation in the ligaments between larger voids that coalesce during intense shearing. A numerical cell-model study is carried out to gain a parametric understanding of the overall material response for different initial conditions of the two void populations...

  8. Investigating Nigerian primary school teachers’ preparedness to adopt personal response system in ESL classroom

    Directory of Open Access Journals (Sweden)

    Alaba Olaoluwakotansibe Agbatogun

    2012-03-01

    Full Text Available This study investigated the extent to which computer literacy dimensions (computer general knowledge, documents and documentations, communication and surfing as well as data inquiry, computer use and academic qualification as independent variables predicted primary school teachers’ attitude towards the integration of Personal Response System in English as a second language (ESL classroom. Seventeen (17 Nigerian primary school teachers trained on why and how to effectively use Personal Response System (PRS in ESL classrooms was the sample for the study. Data for the study were gathered through the use of Clickers Attitude Questionnaire (CAQ, Teachers’ Computer Literacy Questionnaire (TCLQ and Computer Use Questionnaire (CUQ. Descriptive statistics such as simple percentage, mean and standard deviation, and inferential statistics such as Pearson Product Moment Correlation Coefficient, and Multiple regression were used for data analysis at 0.05 significance level. The results show that the teachers’ computer literacy was more in the areas of documents and documentation as well as communication and surfing than in general knowledge and data inquiry. Further findings of the study indicated that general computer knowledge, documents and documentation, communication and surfing, and data inquiry combined to contribute to the prediction of teachers’ attitude towards the integration of PRS. Relatively, documents and documentation dimension was the potent predictor, while data inquiry was not a significant predictor of the outcome variable. Similarly, computer use, computer literacy and academic qualification jointly contributed to the prediction of the teachers’ attitude towards the integration of PRS in ESL classroom. Meanwhile, computer use made the most significant contribution to the prediction of teachers’ attitude towards PRS integration, while academic qualification did not make any significant contribution to the teachers’ attitude

  9. Investigating Nigerian Primary School Teachers’ Preparedness to Adopt Personal Response System in ESL Classroom

    Directory of Open Access Journals (Sweden)

    Alaba Olaoluwakotansibe Agbatogun

    2012-03-01

    Full Text Available This study investigated the extent to which computer literacy dimensions (computer general knowledge, documents and documentations, communication and surfing as well as data inquiry, computer use and academic qualification as independent variables predicted primary school teachers’ attitude towards the integration of Personal Response System in English as a second language (ESL classroom. Seventeen (17 Nigerian primary school teachers trained on why and how to effectively use Personal Response System (PRS in ESL classrooms was the sample for the study. Data for the studywere gathered through the use of Clickers Attitude Questionnaire (CAQ, Teachers’ Computer Literacy Questionnaire (TCLQ and Computer Use Questionnaire (CUQ. Descriptive statistics such as simplepercentage, mean and standard deviation, and inferential statistics such as Pearson Product Moment Correlation Coefficient, and Multiple regression were used for data analysis at 0.05 significance level.The results show that the teachers’ computer literacy was more in the areas of documents and documentation as well as communication and surfing than in general knowledge and data inquiry. Further findings of the study indicated that general computer knowledge, documents anddocumentation, communication and surfing, and data inquiry combined to contribute to the prediction of teachers’ attitude towards the integration of PRS. Relatively, documents and documentation dimension was the potent predictor, while data inquiry was not a significant predictor of the outcome variable. Similarly, computer use, computer literacy and academic qualification jointly contributed to the prediction of the teachers’ attitude towards the integration of PRS in ESL classroom. Meanwhile, computer use made the most significant contribution to the prediction of teachers’ attitude towards PRS integration, while academic qualification did not make any significantcontribution to the teachers’ attitude

  10. Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations.

    Directory of Open Access Journals (Sweden)

    Nori Yoshioka

    Full Text Available Health care workers (HCWs are frequently exposed to hepatitis B virus (HBV infection. The efficacy and safety of immunization with the hepatitis B (HB vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years, and long responders (those who retained positive anti-HBs levels for 3 years and more. We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229, 54.5% after two doses (n = 11, and 4.2% after a single dose (n = 24. Of 213 primary responders, the anti-HBs levels of 95 participants (44.6% fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective

  11. The spectrotemporal filter mechanism of auditory selective attention

    Science.gov (United States)

    Lakatos, Peter; Musacchia, Gabriella; O’Connell, Monica N.; Falchier, Arnaud Y.; Javitt, Daniel C.; Schroeder, Charles E.

    2013-01-01

    SUMMARY While we have convincing evidence that attention to auditory stimuli modulates neuronal responses at or before the level of primary auditory cortex (A1), the underlying physiological mechanisms are unknown. We found that attending to rhythmic auditory streams resulted in the entrainment of ongoing oscillatory activity reflecting rhythmic excitability fluctuations in A1. Strikingly, while the rhythm of the entrained oscillations in A1 neuronal ensembles reflected the temporal structure of the attended stream, the phase depended on the attended frequency content. Counter-phase entrainment across differently tuned A1 regions resulted in both the amplification and sharpening of responses at attended time points, in essence acting as a spectrotemporal filter mechanism. Our data suggest that selective attention generates a dynamically evolving model of attended auditory stimulus streams in the form of modulatory subthreshold oscillations across tonotopically organized neuronal ensembles in A1 that enhances the representation of attended stimuli. PMID:23439126

  12. 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

  13. 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

  14. Effect of Recruitment Methods on Response Rate in a Web-Based Study for Primary Care Physicians: Factorial Randomized Controlled Trial.

    Science.gov (United States)

    So, Ryuhei; Shinohara, Kiyomi; Aoki, Takuya; Tsujimoto, Yasushi; Suganuma, Aya M; Furukawa, Toshi A

    2018-02-08

    Low participation rates are one of the most serious disadvantages of Web-based studies. It is necessary to develop effective strategies to improve participation rates to obtain sufficient data. The objective of this trial was to investigate the effect of emphasizing the incentive in the subject line of the invitation email and the day of the week of sending the invitation email on the participation rate in a Web-based trial. We conducted a 2×2 factorial design randomized controlled trial. We contacted 2000 primary care physicians from members of the Japan Primary Care Association in January 2017 and randomly allocated them to 1 of 4 combinations of 2 subject lines (presence or absence of an emphasis on a lottery for an Amazon gift card worth 3000 yen or approximately US $30) and 2 delivery days (sending the invitation email on Tuesday or Friday). The primary outcome was the response rate defined as the number of participants answering the first page of the questionnaire divided by the number of invitation emails delivered. All outcomes were collected between January 17, 2017, and February 8, 2017. We analyzed data from 1943 out of 2000 participants after excluding those whose email addresses were invalid. The overall response rate was 6.3% (123/1943). There was no significant difference in the response rates between the 2 groups regarding incentive in the subject line: the risk ratio was 1.12 (95% CI 0.80 to 1.58) and the risk difference was 0.7% (95% CI -1.5% to 2.9%). Similarly, there was no significant difference in the response rates between the 2 groups regarding sending the email on Tuesday or Friday: the risk ratio was 0.98 (95% CI 0.70 to 1.38) and the risk difference was -0.1% (95% CI -2.3% to 2.1%). Neither emphasizing the incentive in the subject line of the invitation email nor varying the day of the week the invitation email was sent led to a meaningful increase in response rates in a Web-based trial with primary care physicians. University Hospital

  15. Involvement of three mechanisms in the alteration of cytokine responses by sodium methyldithiocarbamate

    International Nuclear Information System (INIS)

    Pruett, Stephen B.; Fan, Ruping; Zheng, Qiang

    2006-01-01

    Sodium methyldithiocarbamate (SMD) is the third most abundantly used conventional pesticide in the U.S. We recently reported that it alters the induction of cytokine production mediated though Toll-like receptor (TLR) 4 at relevant dosages in mice. Its chemical properties and evidence from the literature suggest thee potential mechanisms of action for this compound. It could either act as a free radical scavenger (by means of its free S - group) or promote oxidation by breaking down to form methylisothiocyanate, which can deplete glutathione. It is a potent copper chelator and may affect the availability of copper to a number of copper-dependent enzymes (including some signaling molecules). SMD induces a classical neuroendocrine stress response characterized by elevated serum corticosterone concentrations, which could affect cytokine production. Although each of these mechanisms could potentially contribute to altered cytokine responses, direct evidence is lacking. The present study was conducted to obtain such evidence. The role of redox balance was investigated by pretreating mice with N-acetyl cysteine (NAC), which increases cellular glutathione concentrations, before administration of SMD. NAC exacerbated the SMD-induced suppression of IL-12 and the SMD-induced enhancement of IL-10 in the serum. The role of copper chelation was investigated by comparing the effects of SMD with an equimolar dose to SMD that was administered in the form of a copper chelation complex. Addition of copper significantly decreased the action of SMD on IL-12 production but not on IL-10 production. The role of the stress response was investigated by pretreating mice with antagonists of corticosterone and catecholamines. This treatment partially prevented the action of SMD on IL-10 and IL-12 in the peritoneal fluid. The results suggest that all of the proposed mechanisms have some role in the alteration of cytokine production by SMD

  16. Immune Responses following Stereotactic Body Radiotherapy for Stage I Primary Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yoshiyasu Maehata

    2013-01-01

    Full Text Available Purpose. Immune responses following stereotactic body radiotherapy (SBRT for stage I non-small cell lung cancer (NSCLC were examined from the point of view of lymphocyte subset counts and natural killer cell activity (NKA. Patients and Methods. Peripheral blood samples were collected from 62 patients at 4 time points between pretreatment and 4 weeks post-treatment for analysis of the change of total lymphocyte counts (TLC and lymphocyte subset counts of CD3+, CD4+, CD8+, CD19+, CD56+, and NKA. In addition, the changes of lymphocyte subset counts were compared between patients with or without relapse. Further, the correlations between SBRT-related parameters and immune response were analyzed for the purpose of revealing the mechanisms of the immune response. Results. All lymphocyte subset counts and NKA at post-treatment and 1 week post-treatment were significantly lower than pre-treatment (P<0.01. No significant differences in the changes of lymphocyte subset counts were observed among patients with or without relapse. The volume of the vertebral body receiving radiation doses of 3 Gy or more (VV3 significantly correlated with the changes of nearly all lymphocyte subset counts. Conclusions. SBRT for stage I NSCLC induced significant immune suppression, and the decrease of lymphocyte subset counts may be associated with exposure of the vertebral bone marrow.

  17. Study on the production mechanism of Co-60 in the primary loop of HTR-10

    International Nuclear Information System (INIS)

    Wang Shouang; Xie Feng; Li Hong; Cao Jianzhu; Li Fu; Wei Liqiang

    2015-01-01

    Co-60 is an activated metallic erosion product, which is very important for waste management and decommissioning work of pressurized water reactor (PWR) power plants. Recent measurement on the samples from the primary loop of HTR-10 indicates the existence of Co-60. In current paper, the preliminary experimental results in HTR-10 will be introduced, and the production mechanism of Co-60 in the pebble bed high temperature gas-cooled reactors will be summarized and compared with that in PWRs and Germany High Temperature Nuclear Reactor (AVR). The further experiments with decomposing the post-irradiation graphite spheres of HTR-10 are put forward, which will promote the further study to testify the production sources of Co-60 and be of great significance in the waste minimization and the decommissioning work of HTR-10. (author)

  18. Multifunctional hybrid diode: Study of photoresponse, high responsivity, and charge injection mechanisms

    Science.gov (United States)

    Singh, Jitendra; Singh, R. G.; Gautam, Subodh K.; Singh, Fouran

    2018-05-01

    A multifunctional hybrid heterojunction diode is developed on porous silicon and its current density-voltage characteristics reveal a good rectification ratio along with other superior parameters such as ideality factor, barrier height and series resistance. The diode also functions as an efficient photodiode to manifest high photosensitivity with high responsivity under illumination with broadband solar light, UV light, and green light. The diode is also carefully scrutinized for its sensitivity and repeatability over many cycles under UV and green light and is found to have a quick response and extremely fast recovery times. The notable responsivity is attributed to the generation of high density of excitons in the depletion region by the absorption of incident photons and their separation by an internal electric field besides an additional photocurrent due to the charging of polymer chains. The mechanisms of generation, injection and transport of charge carriers are explained by developing a schematic energy band diagram. The transport phenomenon of carriers is further investigated from room temperature down to a very low temperature of 10 K. An Arrhenius plot is made to determine the Richardson constant. Various diode parameters as mentioned above are also determined and the dominance of the transport mechanism of charge carriers in different temperature regimes such as diffusion across the junction and/or quantum tunneling through the barriers are explained. The developed multifunction heterojunction hybrid diodes have implications for highly sensitive photodiodes in the UV and visible range of electromagnetic spectrum that can be very promising for efficient optoelectronic devices.

  19. High Electrocatalytic Response of a Mechanically Enhanced NbC Nanocomposite Electrode Towards Hydrogen Evolution Reaction

    KAUST Repository

    Coy, Emerson

    2017-08-22

    Resistant and efficient electrocatalysts for hydrogen evolution reaction (HER) are desired to replace scarce and commercially expensive platinum electrodes. Thin film electrodes of metal-carbides are a promising alternative due to their reduced price and similar catalytic properties. However, most of the studied structures to date neglect long lasting chemical and structural stability, focusing only on electrochemical efficiency. Herein we report on a new approach to easily deposit and control the micro/nanostructure of thin film electrodes based on niobium carbide (NbC) and their electrocatalytic response. We will show that, by improving the mechanical properties of the NbC electrodes, microstructure and mechanical resilience can be obtained whilst maintaining high electro catalytic response. We also address the influence of other parameters such as conductivity and chemical composition on the overall performance of the thin film electrodes. Finally, we show that nanocomposite NbC electrodes are promising candidates towards HER , and furthermore, that the methodology presented here is suitable to produce other transition metal carbides (TM-C) with improved catalytic and mechanical properties.

  20. Transport coefficients and mechanical response in hard-disk colloidal suspensions

    Science.gov (United States)

    Zhang, Bo-Kai; Li, Jian; Chen, Kang; Tian, Wen-De; Ma, Yu-Qiang

    2016-11-01

    We investigate the transport properties and mechanical response of glassy hard disks using nonlinear Langevin equation theory. We derive expressions for the elastic shear modulus and viscosity in two dimensions on the basis of thermal-activated barrier-hopping dynamics and mechanically accelerated motion. Dense hard disks exhibit phenomena such as softening elasticity, shear-thinning of viscosity, and yielding upon deformation, which are qualitatively similar to dense hard-sphere colloidal suspensions in three dimensions. These phenomena can be ascribed to stress-induced “landscape tilting”. Quantitative comparisons of these phenomena between hard disks and hard spheres are presented. Interestingly, we find that the density dependence of yield stress in hard disks is much more significant than in hard spheres. Our work provides a foundation for further generalizing the nonlinear Langevin equation theory to address slow dynamics and rheological behavior in binary or polydisperse mixtures of hard or soft disks. Project supported by the National Basic Research Program of China (Grant No. 2012CB821500) and the National Natural Science Foundation of China (Grant Nos. 21374073 and, 21574096).

  1. Responses and mechanisms of positive electron affinity molecules in the N2 mode of the thermionic ionization detector and the electron-capture detector

    International Nuclear Information System (INIS)

    Jones, C.S.

    1989-01-01

    Very little knowledge has been acquired in the past on the mechanistic pathway by which molecules respond in the N 2 mode of the thermionic ionization detector. An attempt is made here to elucidate the response mechanism of the detector. The basic response mechanisms are known for the electron capture detector, and an attempt is made to identify the certain mechanism by which selected molecules respond. The resonance electron capture rate constant has been believed to be temperature independent, and investigations of the temperature dependence of electron capture responses are presented. Mechanisms for the N 2 mode of the thermionic ionization detector have been proposed by examining the detector response to positive electron affinity molecules and by measurement of the ions produced by the detector. Electron capture mechanisms for selected molecules have been proposed by examining their temperature dependent responses in the electron capture detector and negative ion mass spectra of the samples. In studies of the resonance electron capture rate constant, the relative responses of selected positive electron affinity molecules and their temperature dependent responses were investigated. Positive electron affinity did not guarantee large responses in the N 2 mode thermionic ionization detector. High mass ions were measured following ionization of samples in the detector. Responses in the electron capture detector varied with temperature and electron affinity

  2. 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

  3. Primary Sjogren's syndrome associated with inappropriate ...

    African Journals Online (AJOL)

    A patient in whom primary Sjogren's syndrome and inappropriate antiduretic hormone secretion were associated is reported. This is the first report of such an association. The possible pathophysiological mechanisms are discussed and vasculitis proposed as the underlying pathogenetic mechanism.

  4. Mechanism-Based Modeling of Gastric Emptying Rate and Gallbladder Emptying in Response to Caloric Intake

    DEFF Research Database (Denmark)

    Guiastrennec, B; Sonne, David Peick; Hansen, M

    2016-01-01

    Bile acids released postprandially modify the rate and extent of absorption of lipophilic compounds. The present study aimed to predict gastric emptying (GE) rate and gallbladder emptying (GBE) patterns in response to caloric intake. A mechanism-based model for GE, cholecystokinin plasma concentr......Bile acids released postprandially modify the rate and extent of absorption of lipophilic compounds. The present study aimed to predict gastric emptying (GE) rate and gallbladder emptying (GBE) patterns in response to caloric intake. A mechanism-based model for GE, cholecystokinin plasma...... concentrations, and GBE was developed on data from 33 patients with type 2 diabetes and 33 matched nondiabetic individuals who were administered various test drinks. A feedback action of the caloric content entering the proximal small intestine was identified for the rate of GE. The cholecystokinin...

  5. TRPM8 mechanism of autonomic nerve response to cold in respiratory airway

    Directory of Open Access Journals (Sweden)

    Wang Cong-Yi

    2008-06-01

    Full Text Available Abstract Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.

  6. Numerical Simulation of Electro-Mechanical Impedance Response in Cable-Anchor Connection Interface

    International Nuclear Information System (INIS)

    Nguyen, Khac Duy; Kim, Jeong Tae

    2011-01-01

    In this study, a finite element(FE) analysis on electro-mechanical impedance response of cable-anchor connection interface under various anchor force is presented. In order to achieve the objective, the following approaches are implemented. Firstly, an interface washer coupled with piezoelectric(PZT) material is designed for monitoring cable-force loss. The interface washer is a small aluminum plate on which a PZT patch is surface-bonded. Cable-force loss could be monitored by installing the interface washer between the anchor plate and the anchorage of cable-anchor connection and examining the changes of impedance of the interface washer. Secondly, a FE model for cable-anchor connection is established to examine the effect of cable-force on impedance response of interface washer. Also, the effects of geometrical and material properties of the interface washer on impedance responses under various cable-forces are investigated. Finally, validation of the FE analysis is experimentally evaluated by a lab-scale cable-anchor connection

  7. Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: Insights into a possible mechanism for analgesia.

    Science.gov (United States)

    Pawela, Christopher P; Kramer, Jeffery M; Hogan, Quinn H

    2017-02-15

    Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field stimulation - GFS) is an emerging therapeutic approach to alleviate chronic pain. Here we describe blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat model that replicates clinical GFS using an electrode implanted adjacent to the DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD fMRI response in brain regions previously associated with sensory and pain-related response, such as primary/secondary somatosensory cortex, retrosplenial granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus, and amygdala. These regions differentially demonstrated either positive or negative correlation to the acute noxious stimulation paradigm, in agreement with previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the global BOLD response to noxious stimulation in these regions. This BOLD signal attenuation persisted for 20minutes after the GFS was discontinued. Control experiments in sham-operated animals showed that the attenuation was not due to the effect of repetitive noxious stimulation. Additional control experiments also revealed minimal BOLD fMRI response to GFS at therapeutic intensity when presented in a standard block-design paradigm. High intensity GFS produced a BOLD signal map similar to acute noxious stimulation when presented in a block-design. These findings are the first to identify the specific brain region responses to neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced treatment of chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Recent advances in primary Sjogren's syndrome [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Nicholas Holdgate

    2016-06-01

    Full Text Available Primary Sjögren’s syndrome, a chronic inflammatory process, is among the most commonly occurring rheumatologic diseases. The clinical hallmark of this disease is exocrine gland dysfunction, resulting predominately in dry eyes and dry mouth. However, the disease often extends beyond the exocrine glands to seriously affect other organs systems, such as the lungs, kidneys, and nervous system. Moreover, patients with primary Sjögren’s syndrome develop non-Hodgkin’s B cell lymphoma at a substantially higher rate than the general population. New research has improved our understanding of disease mechanisms, with notable advances in our knowledge about the genetic susceptibility of disease, the molecular details of the chronic inflammatory response in the salivary glands, and the complex role of the type 1 interferon pathway. The pipeline of drugs under development for the treatment of primary Sjögren’s syndrome is enriched with novel biologics and small molecular entities targeting the pathogenic process. Herein, we summarize the latest advances in elucidating the pathogenesis of primary Sjögren’s syndrome and highlight new drugs in clinical development aiming to reverse the glandular dysfunction and favorably impact the systemic features of this disease.

  9. Neural responses in the primary auditory cortex of freely behaving cats while discriminating fast and slow click-trains.

    Science.gov (United States)

    Dong, Chao; Qin, Ling; Liu, Yongchun; Zhang, Xinan; Sato, Yu

    2011-01-01

    Repeated acoustic events are ubiquitous temporal features of natural sounds. To reveal the neural representation of the sound repetition rate, a number of electrophysiological studies have been conducted on various mammals and it has been proposed that both the spike-time and firing rate of primary auditory cortex (A1) neurons encode the repetition rate. However, previous studies rarely examined how the experimental animals perceive the difference in the sound repetition rate, and a caveat to these experiments is that they compared physiological data obtained from animals with psychophysical data obtained from humans. In this study, for the first time, we directly investigated acoustic perception and the underlying neural mechanisms in the same experimental animal by examining spike activities in the A1 of free-moving cats while performing a Go/No-go task to discriminate the click-trains at different repetition rates (12.5-200 Hz). As reported by previous studies on passively listening animals, A1 neurons showed both synchronized and non-synchronized responses to the click-trains. We further found that the neural performance estimated from the precise temporal information of synchronized units was good enough to distinguish all 16.7-200 Hz from the 12.5 Hz repetition rate; however, the cats showed declining behavioral performance with the decrease of the target repetition rate, indicating an increase of difficulty in discriminating two slower click-trains. Such behavioral performance was well explained by the firing rate of some synchronized and non-synchronized units. Trial-by-trial analysis indicated that A1 activity was not affected by the cat's judgment of behavioral response. Our results suggest that the main function of A1 is to effectively represent temporal signals using both spike timing and firing rate, while the cats may read out the rate-coding information to perform the task in this experiment.

  10. Neural responses in the primary auditory cortex of freely behaving cats while discriminating fast and slow click-trains.

    Directory of Open Access Journals (Sweden)

    Chao Dong

    Full Text Available Repeated acoustic events are ubiquitous temporal features of natural sounds. To reveal the neural representation of the sound repetition rate, a number of electrophysiological studies have been conducted on various mammals and it has been proposed that both the spike-time and firing rate of primary auditory cortex (A1 neurons encode the repetition rate. However, previous studies rarely examined how the experimental animals perceive the difference in the sound repetition rate, and a caveat to these experiments is that they compared physiological data obtained from animals with psychophysical data obtained from humans. In this study, for the first time, we directly investigated acoustic perception and the underlying neural mechanisms in the same experimental animal by examining spike activities in the A1 of free-moving cats while performing a Go/No-go task to discriminate the click-trains at different repetition rates (12.5-200 Hz. As reported by previous studies on passively listening animals, A1 neurons showed both synchronized and non-synchronized responses to the click-trains. We further found that the neural performance estimated from the precise temporal information of synchronized units was good enough to distinguish all 16.7-200 Hz from the 12.5 Hz repetition rate; however, the cats showed declining behavioral performance with the decrease of the target repetition rate, indicating an increase of difficulty in discriminating two slower click-trains. Such behavioral performance was well explained by the firing rate of some synchronized and non-synchronized units. Trial-by-trial analysis indicated that A1 activity was not affected by the cat's judgment of behavioral response. Our results suggest that the main function of A1 is to effectively represent temporal signals using both spike timing and firing rate, while the cats may read out the rate-coding information to perform the task in this experiment.

  11. Three-dimensional analysis of the anatomical growth response of European conifers to mechanical disturbance.

    Science.gov (United States)

    Schneuwly, Dominique M; Stoffel, Markus; Dorren, Luuk K A; Berger, Frédéric

    2009-10-01

    Studies on tree reaction after wounding were so far based on artificial wounding or chemical treatment. For the first time, type, spread and intensity of anatomical responses were analyzed and quantified in naturally disturbed Larix decidua Mill., Picea abies (L.) Karst. and Abies alba Mill. trees. The consequences of rockfall impacts on increment growth were assessed at the height of the wounds, as well as above and below the injuries. A total of 16 trees were selected on rockfall slopes, and growth responses following 54 wounding events were analyzed on 820 cross-sections. Anatomical analysis focused on the occurrence of tangential rows of traumatic resin ducts (TRD) and on the formation of reaction wood. Following mechanical disturbance, TRD production was observed in 100% of L. decidua and P. abies wounds. The radial extension of TRD was largest at wound height, and they occurred more commonly above, rather than below, the wounds. For all species, an intra-annual radial shift of TRD was observed with increasing axial distance from wounds. Reaction wood was formed in 87.5% of A. alba following wounding, but such cases occurred only in 7.7% of L. decidua. The results demonstrate that anatomical growth responses following natural mechanical disturbance differ significantly from the reactions induced by artificial stimuli or by decapitation. While the types of reactions remain comparable between the species, their intensity, spread and persistence disagree considerably. We also illustrate that the external appearance of wounds does not reflect an internal response intensity. This study reveals that disturbance induced under natural conditions triggers more intense and more widespread anatomical responses than that induced under artificial stimuli, and that experimental laboratory tests considerably underestimate tree response.

  12. Transforaminal epidural steroid injections influence Mechanical Diagnosis and Therapy (MDT) pain response classification in candidates for lumbar herniated disc surgery.

    Science.gov (United States)

    van Helvoirt, Hans; Apeldoorn, Adri T; Knol, Dirk L; Arts, Mark P; Kamper, Steven J; van Tulder, Maurits W; Ostelo, Raymond W

    2016-04-27

    Prospective cohort study. Although lumbar radiculopathy is regarded as a specific diagnosis, the most effective treatment strategy is unclear. Commonly used treatments include transforaminal epidural steroid injections (TESIs) and Mechanical Diagnosis & Therapy (MDT), but no studies have investigated the effectiveness of this combination. MDT differentiates pain centralization (C) from non-centralization (NC), which indicates good vs. poor prognostic validity respectively. The main aims were 1) to determine changes in Mechanical Diagnosis and Therapy (MDT) pain response classifications after transforaminal epidural steroid injections (TESIs) in candidates for lumbar herniated disc surgery and 2) to evaluate differences in short and long term outcomes for patients with different pain response classifications. Candidates for lumbar herniated disc surgery were assessed with a MDT protocol and their pain response classified as centralizing or peripheralizing. For this study,only patients were eligible who showed a peripheralizing pain response at intake. All patients then received TESIs and were reassessed and classified using the MDT protocol, into groups according to pain response (resolved, centralizing, peripheralizing with less pain and peripheralising with severe pain). After receiving targeted treatment based on pain response after TESIs, ranging from advice, MDT or surgery, follow-up assessments were completed at discharge and at 12 months. The primary outcomes were disability (Roland-Morris Disability Questionnaire [RMDQ] for Sciatica), pain severity in leg (visual analogue scale [VAS], 0-100) and global perceived effect (GPE). Linear mixed-models were used to determine between-groups differences in outcome. A total of 77 patients with lumbar disc herniation and peripheralizing symptoms were included. Patients received an average of 2 (SD 0.7) TESIs. After TESIs, 17 patients (22%) were classified as peripheralizing with continuing severe pain.These patients

  13. 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.

  14. Imaging of primary pediatric lymphoma of bone

    International Nuclear Information System (INIS)

    Milks, Kathryn S.; McLean, Thomas W.; Anthony, Evelyn Y.

    2016-01-01

    Primary pediatric bone lymphoma is a rare form of non-Hodgkin lymphoma. Unlike nodal forms of lymphoma, imaging abnormalities in lymphoma of bone do not resolve rapidly in conjunction with treatment and radiologic findings can remain abnormal for years, making it difficult to evaluate treatment response. To evaluate the utility of imaging in assessment of patients with primary pediatric bone lymphoma. At our institution between 2004 and 2013, six cases of pathology-proven primary pediatric bone lymphoma were diagnosed. Retrospective chart review was performed to assess imaging utilization. Our data were qualitatively compared with existing literature to construct an algorithm for imaging patients with primary lymphoma of bone. Imaging evaluation of patients with primary pediatric bone lymphoma was highly variable at our institution. Conventional imaging was routinely used to evaluate response to treatment, despite lack of appreciable osseous change. Imaging in the absence of symptoms did not alter clinical management. Only positron emission tomography CT (PET/CT) proved capable of demonstrating imaging changes from the pretreatment to the post-treatment scans that were consistent with the clinical response to treatment. Surveillance imaging is likely unnecessary in patients with a known diagnosis of pediatric lymphoma of bone. Pretreatment and post-treatment PET/CT is likely sufficient to assess response. There is little data to support the use of interim and surveillance PET/CT. (orig.)

  15. Susceptibility and response of human blood monocyte subsets to primary dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Kok Loon Wong

    Full Text Available Human blood monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood monocytes are heterogeneous and divided into CD16(- and CD16(+ subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if monocyte subsets differentially contribute to dengue protection and pathogenesis. Here, we compared the susceptibility and response of the human CD16(- and CD16(+ blood monocyte subsets to primary dengue virus in vitro. We found that both monocyte subsets were equally susceptible to dengue virus (DENV2 NGC, and capable of supporting the initial production of new infective virus particles. Both monocyte subsets produced anti-viral factors, including IFN-α, CXCL10 and TRAIL. However, CD16(+ monocytes were the major producers of inflammatory cytokines and chemokines in response to dengue virus, including IL-1β, TNF-α, IL-6, CCL2, 3 and 4. The susceptibility of both monocyte subsets to infection was increased after IL-4 treatment, but this increase was more profound for the CD16(+ monocyte subset, particularly at early time points after virus exposure. These findings reveal the differential role that monocyte subsets might play during dengue disease.

  16. Analysis of differential lipofection efficiency in primary and established myoblasts.

    Science.gov (United States)

    Pampinella, Francesca; Lechardeur, Delphine; Zanetti, Elena; MacLachlan, Ian; Benharouga, Mohammed; Lukacs, Gergely L; Vitiello, Libero

    2002-02-01

    In this study we have compared the process of lipid-mediated transfection in primary and established myoblasts, in an attempt to elucidate the mechanisms responsible for the scarce transfectability of the former. We determined the metabolic stability of cytoplasmically injected and lipofected DNA in primary and established myoblasts and carried out a comparative time course analysis of luciferase reporter-gene expression and DNA stability. The efficiency of the transcription-translation machinery of the two cell types was compared by intranuclear injection of naked plasmid DNA encoding luciferase. Subcellular colocalization of fluorescein-labeled lipopolyplexes with specific endosomal and lysosomal markers was performed by confocal microscopy to monitor the intracellular trafficking of plasmid DNA during transfection. The metabolic stability of plasmid DNA was similar in primary and established myoblasts after both lipofection and cytoplasmic injection. In both cell types, lipofection had no detectable effect on the rate of cell proliferation. Confocal analysis showed that nuclear translocation of transfected DNA coincided with localization in a compartment devoid of endosome- or lysosome-specific marker proteins. The residency time of plasmid DNA in this compartment differed for primary and established myoblasts. Our findings suggest that the lower transfectability of primary myoblasts is mostly due to a difference in the intracellular delivery pathway that correlates with more rapid delivery of internalized complex to the lysosomal compartment.

  17. [Likeness between respiratory responses on CO2 in conditions of natural breathing and voluntary-controlled mechanical ventilation].

    Science.gov (United States)

    Pogodin, M A; Granstrem, M P; Dimitrienko, A I

    2007-04-01

    We did Read CO2 rebreathing tests in 8 adult males. Both at natural breathing, and at self-controlled mechanical ventilation, volunteers increased ventilation proportionally to growth end-tidal PCO2. Inside individual distinctions of responses to CO2 during controlled mechanical ventilation are result of the voluntary motor control.

  18. 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.

  19. Fatigue responses of lead zirconate titanate stacks under semibipolar electric cycling with mechanical preload

    Science.gov (United States)

    Wang, Hong; Cooper, Thomas A.; Lin, Hua-Tay; Wereszczak, Andrew A.

    2010-10-01

    Lead zirconate titanate (PZT) stacks that had an interdigital internal electrode configuration were tested to more than 108 cycles. A 100 Hz semibipolar sine wave with a field range of +4.5/-0.9 kV/mm was used in cycling with a concurrently-applied 20 MPa preload. Significant reductions in piezoelectric and dielectric responses were observed during the cycling depending on the measuring condition. Extensive partial discharges were also observed. These surface events resulted in the erosion of external electrode and the exposure of internal electrodes. Sections prepared by sequential polishing technique revealed a variety of damage mechanisms including delaminations, pores, and etch grooves. The scale of damage was correlated with the degree of fatigue-induced reduction in piezoelectric and dielectric responses. The results from this study demonstrate the feasibility of using a semibipolar mode to drive a PZT stack under a mechanical preload and illustrate the potential fatigue and damages of the stack in service.

  20. A qualitative study of sign-out processes between primary and on-call residents: relationships in information exchange, responsibility and accountability.

    Science.gov (United States)

    Lee, Soo-Hoon; Fisher, Dale A; Mah, Heidi; Goh, Wei-Ping; Phan, Phillip H

    2017-10-01

    To review a quality improvement event on the process of sign-outs between the primary and on-call residents. A retrospective qualitative study using semi-structured interviews. A tertiary academic medical center in Singapore with 283 inpatient Medicine beds served by 28 consultants, 29 registrars, 45 residents and 30 interns during the day but 5 residents and 3 interns at night. Residents, registrars and consultants. Quality improvement event on sign-out. Effectiveness of sign-out comprises exchange of patient information, professional responsibility and task accountability. The following process of sign-outs was noted. Primary teams were accountable to the on-call resident by selecting at-risk patients and preparing contingency plans for sign-out. Structured information exchanged included patient history, active problems and plans of care. On-call residents took ownership of at-risk patients by actively asking questions during sign-out and reporting back the agreed care plan. On-call residents were accountable to the primary team by reporting back at-risk patients the next day. A structured information exchange at sign-out increased the on-call resident's ability to care for at-risk patients when it was supported by two-way transfers of responsibility and accountability. © The Author 2017. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  1. Neural mechanisms linking social status and inflammatory responses to social stress.

    Science.gov (United States)

    Muscatell, Keely A; Dedovic, Katarina; Slavich, George M; Jarcho, Michael R; Breen, Elizabeth C; Bower, Julienne E; Irwin, Michael R; Eisenberger, Naomi I

    2016-06-01

    Social stratification has important implications for health and well-being, with individuals lower in standing in a hierarchy experiencing worse outcomes than those higher up the social ladder. Separate lines of past research suggest that alterations in inflammatory processes and neural responses to threat may link lower social status with poorer outcomes. This study was designed to bridge these literatures to investigate the neurocognitive mechanisms linking subjective social status and inflammation. Thirty-one participants reported their subjective social status, and underwent a functional magnetic resonance imaging scan while they were socially evaluated. Participants also provided blood samples before and after the stressor, which were analysed for changes in inflammation. Results showed that lower subjective social status was associated with greater increases in inflammation. Neuroimaging data revealed lower subjective social status was associated with greater neural activity in the dorsomedial prefrontal cortex (DMPFC) in response to negative feedback. Finally, results indicated that activation in the DMPFC in response to negative feedback mediated the relation between social status and increases in inflammatory activity. This study provides the first evidence of a neurocognitive pathway linking subjective social status and inflammation, thus furthering our understanding of how social hierarchies shape neural and physiological responses to social interactions. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. 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...

  3. Various bio-mechanical factors affecting heat generation during osteotomy preparation: A systematic review.

    Science.gov (United States)

    Chauhan, Chirag J; Shah, Darshana N; Sutaria, Foram B

    2018-01-01

    As implant site preparation and bone are critical precursors to primary healing, thermal and mechanical damage to the bone must be minimized during the preparation of the implant site. Moreover, excessively traumatic surgery can adversely affect the maturation of bone tissue at the bone/implant interface and consequently diminish the predictability of osseointegration. So, this study was carried out to evaluate the various biological and mechanical factors responsible for heat generation during osteotomy site preparation to reduce the same for successful osseointegration of dental implants. A broad search of the dental literature in PubMed added by manual search was performed for articles published between 1992 and December 2015. Various bio-mechanical factors related to dental implant osteotomy preparation such as dental implant drill designs/material/wear, drilling methods, type of irrigation, and bone quality were reviewed. Titles and abstracts were screened and articles which fulfilled the inclusion criteria were selected for a full-text reading. The initial database search yielded 123 titles, of which 59 titles were discarded after reading the titles and abstracts, 30 articles were again excluded based on inclusion and exclusion criteria, and finally 34 articles were selected for data extraction. Many biological and mechanical factors responsible for heat generation were found. Literatures of this review study have indicated that there are various bio-mechanical reasons, which affect the temperature rise during osteotomy and suggest that the amount of heat generation is a multifactorial in nature and it should be minimized for better primary healing of the implant site.

  4. Photochemical modeling in California with two chemical mechanisms: model intercomparison and response to emission reductions.

    Science.gov (United States)

    Cai, Chenxia; Kelly, James T; Avise, Jeremy C; Kaduwela, Ajith P; Stockwell, William R

    2011-05-01

    An updated version of the Statewide Air Pollution Research Center (SAPRC) chemical mechanism (SAPRC07C) was implemented into the Community Multiscale Air Quality (CMAQ) version 4.6. CMAQ simulations using SAPRC07C and the previously released version, SAPRC99, were performed and compared for an episode during July-August, 2000. Ozone (O3) predictions of the SAPRC07C simulation are generally lower than those of the SAPRC99 simulation in the key areas of central and southern California, especially in areas where modeled concentrations are greater than the federal 8-hr O3 standard of 75 parts per billion (ppb) and/or when the volatile organic compound (VOC)/nitrogen oxides (NOx) ratio is less than 13. The relative changes of ozone production efficiency (OPE) against the VOC/NOx ratio at 46 sites indicate that the OPE is reduced in SAPRC07C compared with SAPRC99 at most sites by as much as approximately 22%. The SAPRC99 and SAPRC07C mechanisms respond similarly to 20% reductions in anthropogenic VOC emissions. The response of the mechanisms to 20% NOx emissions reductions can be grouped into three cases. In case 1, in which both mechanisms show a decrease in daily maximum 8-hr O3 concentration with decreasing NOx emissions, the O3 decrease in SAPRC07C is smaller. In case 2, in which both mechanisms show an increase in O3 with decreasing NOx emissions, the O3 increase is larger in SAPRC07C. In case 3, SAPRC07C simulates an increase in O3 in response to reduced NOx emissions whereas SAPRC99 simulates a decrease in O3 for the same region. As a result, the areas where NOx controls would be disbeneficial are spatially expanded in SAPRC07C. Although the results presented here are valuable for understanding differences in predictions and model response for SAPRC99 and SAPRC07C, the study did not evaluate the impact of mechanism differences in the context of the U.S. Environmental Protection Agency's guidance for using numerical models in demonstrating air quality attainment

  5. Is mechanical dyssynchrony still a major determinant for responses after cardiac resynchronization therapy?

    International Nuclear Information System (INIS)

    Zhang Qing; Yu Cheuk Man

    2011-01-01

    The assessment of mechanical dyssynchrony by advanced echocardiographic technologies and its importance in selecting more appropriate candidates for cardiac resynchronization therapy (CRT) have been disputed, after the announcement of the Predictors of Response to CRT (PROSPECT) trial, as the first evidence derived from a multicenter study. However, attempts in this field have never been stopped, as it appears that the fundamental mechanism of CRT is the correction of dyssynchrony where the detection of baseline dyssynchrony is of particular significance. The QRS width provides simple but very limited information. On the other hand, non-invasive imaging tools such as echocardiography have the capacity for more detailed analysis of mechanical dyssynchrony. We reviewed a number of clinical studies published in the post-PROSPECT era, designed to figure out a predictive algorithm where dyssynchrony measure is included, for identifying the most suitable patients before device implantation. From the analysis, mechanical dyssynchrony remains to be a major determinant for clinical outcomes after CRT, although discrepancies have arisen with respect to the single-center nature, echocardiographic methodologies, and relative merit when compared with other predicting factors. (author)

  6. Mechanical response of common millet (Panicum miliaceum) seeds under quasi-static compression: Experiments and modeling.

    Science.gov (United States)

    Hasseldine, Benjamin P J; Gao, Chao; Collins, Joseph M; Jung, Hyun-Do; Jang, Tae-Sik; Song, Juha; Li, Yaning

    2017-09-01

    The common millet (Panicum miliaceum) seedcoat has a fascinating complex microstructure, with jigsaw puzzle-like epidermis cells articulated via wavy intercellular sutures to form a compact layer to protect the kernel inside. However, little research has been conducted on linking the microstructure details with the overall mechanical response of this interesting biological composite. To this end, an integrated experimental-numerical-analytical investigation was conducted to both characterize the microstructure and ascertain the microscale mechanical properties and to test the overall response of kernels and full seeds under macroscale quasi-static compression. Scanning electron microscopy (SEM) was utilized to examine the microstructure of the outer seedcoat and nanoindentation was performed to obtain the material properties of the seedcoat hard phase material. A multiscale computational strategy was applied to link the microstructure to the macroscale response of the seed. First, the effective anisotropic mechanical properties of the seedcoat were obtained from finite element (FE) simulations of a microscale representative volume element (RVE), which were further verified from sophisticated analytical models. Then, macroscale FE models of the individual kernel and full seed were developed. Good agreement between the compression experiments and FE simulations were obtained for both the kernel and the full seed. The results revealed the anisotropic property and the protective function of the seedcoat, and showed that the sutures of the seedcoat play an important role in transmitting and distributing loads in responding to external compression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Response characteristics of HPR1000 primary circuit under different working conditions of the atmospheric relief system after SBLOCA

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Danting, E-mail: suidanting@163.com [School of Nuclear Science and Engineering, North China Electric Power University, Beijing (China); Beijing Key Laboratory of Passive Safety Technology for Nuclear Energy, North China Electric Power University, Beijing (China); Lu, Daogang [School of Nuclear Science and Engineering, North China Electric Power University, Beijing (China); Beijing Key Laboratory of Passive Safety Technology for Nuclear Energy, North China Electric Power University, Beijing (China); Shang, Changzhong; Wei, Yuanyuan [China Nuclear Power Design Co., ltd (ShenZhen), Shenzhen (China); Zhang, Xianjie [School of Nuclear Science and Engineering, North China Electric Power University, Beijing (China); Beijing Key Laboratory of Passive Safety Technology for Nuclear Energy, North China Electric Power University, Beijing (China)

    2017-04-01

    Highlights: • Response of HPR1000 under different VDA conditions after SBLOCA was investigated. • Activation of VDA can trigger ACCU SI earlier with a critical point exists. • VDA capability design should compromise the critical point with reactivity feedback. - Abstract: To cope with SBLOCA in absence of High-Head Safety Injection (HHSI) from design of HPR1000, atmospheric relief system (originally named as VDA in French) is uniquely designed to help to trigger Middle Head Safety Injection (MHSI) or Low Head Safety Injection (LHSI) earlier through cooling primary system quickly after SBLOCA. To make the best use of VDA decay heat removal capability, primary and secondary system of HPR1000 was modeled with RELAP5/SCDAP computer code. After steady-state initialization, a cold leg 30 mm break SBLOCA was simulated with six simulation conditions and five additional cases including availability of ACCU, different VDA discharge locations and area. Response characteristics of primary loop under different VDA working conditions are investigated. Pressurizer pressure decreases rapidly to lower level to trigger the reactor scram, VDA activation and accumulator safety injection sequently. Peak cladding temperature is 899.45 K occurring at 222 s, which is far below the safety limit. Activation of VDA can trigger ACCU SI earlier with a critical point, while positive reactivity will be introduced due to negative moderator temperature effect and Doppler effect. Larger VDA discharge capability will introduce larger reactivity feedback, as well as induce lower core level and SG level. It's suggested that VDA discharge condition should be chosen before the critical point, with the compromise with reactivity feedback introduced due to the negative moderator temperature effect.

  8. Response characteristics of HPR1000 primary circuit under different working conditions of the atmospheric relief system after SBLOCA

    International Nuclear Information System (INIS)

    Sui, Danting; Lu, Daogang; Shang, Changzhong; Wei, Yuanyuan; Zhang, Xianjie

    2017-01-01

    Highlights: • Response of HPR1000 under different VDA conditions after SBLOCA was investigated. • Activation of VDA can trigger ACCU SI earlier with a critical point exists. • VDA capability design should compromise the critical point with reactivity feedback. - Abstract: To cope with SBLOCA in absence of High-Head Safety Injection (HHSI) from design of HPR1000, atmospheric relief system (originally named as VDA in French) is uniquely designed to help to trigger Middle Head Safety Injection (MHSI) or Low Head Safety Injection (LHSI) earlier through cooling primary system quickly after SBLOCA. To make the best use of VDA decay heat removal capability, primary and secondary system of HPR1000 was modeled with RELAP5/SCDAP computer code. After steady-state initialization, a cold leg 30 mm break SBLOCA was simulated with six simulation conditions and five additional cases including availability of ACCU, different VDA discharge locations and area. Response characteristics of primary loop under different VDA working conditions are investigated. Pressurizer pressure decreases rapidly to lower level to trigger the reactor scram, VDA activation and accumulator safety injection sequently. Peak cladding temperature is 899.45 K occurring at 222 s, which is far below the safety limit. Activation of VDA can trigger ACCU SI earlier with a critical point, while positive reactivity will be introduced due to negative moderator temperature effect and Doppler effect. Larger VDA discharge capability will introduce larger reactivity feedback, as well as induce lower core level and SG level. It's suggested that VDA discharge condition should be chosen before the critical point, with the compromise with reactivity feedback introduced due to the negative moderator temperature effect.

  9. Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

    Science.gov (United States)

    Warters, Raymond L.; Packard, Ann T.; Kramer, Gwen F.; Gaffney, David K.; Moos, Philip J.

    2009-01-01

    Although skin is usually exposed during human exposures to ionizing radiation, there have been no thorough examinations of the transcriptional response of skin fibroblasts and keratinocytes to radiation. The transcriptional response of quiescent primary fibroblasts and keratinocytes exposed to from 10 cGy to 5 Gy and collected 4 h after treatment was examined. RNA was isolated and examined by microarray analysis for changes in the levels of gene expression. Exposure to ionizing radiation altered the expression of 279 genes across both cell types. Changes in RNA expression could be arranged into three main categories: (1) changes in keratinocytes but not in fibroblasts, (2) changes in fibroblasts but not in keratinocytes, and (3) changes in both. All of these changes were primarily of p53 target genes. Similar radiation-induced changes were induced in immortalized fibroblasts or keratinocytes. In separate experiments, protein was collected and analyzed by Western blotting for expression of proteins observed in microarray experiments to be overexpressed at the mRNA level. Both Q-PCR and Western blot analysis experiments validated these transcription changes. Our results are consistent with changes in the expression of p53 target genes as indicating the magnitude of cell responses to ionizing radiation. PMID:19580510

  10. Uncovering the inertia of dislocation motion and negative mechanical response in crystals.

    Science.gov (United States)

    Tang, Yizhe

    2018-01-09

    Dislocations are linear defects in crystals and their motion controls crystals' mechanical behavior. The dissipative nature of dislocation propagation is generally accepted although the specific mechanisms are still not fully understood. The inertia, which is undoubtedly the nature of motion for particles with mass, seems much less convincing for configuration propagation. We utilize atomistic simulations in conditions that minimize dissipative effects to enable uncovering of the hidden nature of dislocation motion, in three typical model metals Mg, Cu and Ta. We find that, with less/no dissipation, dislocation motion is under-damped and explicitly inertial at both low and high velocities. The inertia of dislocation motion is intrinsic, and more fundamental than the dissipative nature. The inertia originates from the kinetic energy imparted from strain energy and stored in the moving core. Peculiar negative mechanical response associated with the inertia is also discovered. These findings shed light on the fundamental nature of dislocation motion, reveal the underlying physics, and provide a new physical explanation for phenomena relevant to high-velocity dislocations.

  11. Distinction between added-energy and phase-resetting mechanisms in non-invasively detected somatosensory evoked responses.

    Science.gov (United States)

    Fedele, T; Scheer, H-J; Burghoff, M; Waterstraat, G; Nikulin, V V; Curio, G

    2013-01-01

    Non-invasively recorded averaged event-related potentials (ERP) represent a convenient opportunity to investigate human brain perceptive and cognitive processes. Nevertheless, generative ERP mechanisms are still debated. Two previous approaches have been contested in the past: the added-energy model in which the response raises independently from the ongoing background activity, and the phase-reset model, based on stimulus-driven synchronization of oscillatory ongoing activity. Many criteria for the distinction of these two models have been proposed, but there is no definitive methodology to disentangle them, owing also to the limited information at the single trial level. Here, we propose a new approach combining low-noise EEG technology and multivariate decomposition techniques. We present theoretical analyses based on simulated data and identify in high-frequency somatosensory evoked responses an optimal target for the distinction between the two mechanisms.

  12. Software design to calculate and simulate the mechanical response of electromechanical lifts

    Science.gov (United States)

    Herrera, I.; Romero, E.

    2016-05-01

    Lift engineers and lift companies which are involved in the design process of new products or in the research and development of improved components demand a predictive tool of the lift slender system response before testing expensive prototypes. A method for solving the movement of any specified lift system by means of a computer program is presented. The mechanical response of the lift operating in a user defined installation and configuration, for a given excitation and other configuration parameters of real electric motors and its control system, is derived. A mechanical model with 6 degrees of freedom is used. The governing equations are integrated step by step through the Meden-Kutta algorithm in the MATLAB platform. Input data consists on the set point speed for a standard trip and the control parameters of a number of controllers and lift drive machines. The computer program computes and plots very accurately the vertical displacement, velocity, instantaneous acceleration and jerk time histories of the car, counterweight, frame, passengers/loads and lift drive in a standard trip between any two floors of the desired installation. The resulting torque, rope tension and deviation of the velocity plot with respect to the setpoint speed are shown. The software design is implemented in a demo release of the computer program called ElevaCAD. Further on, the program offers the possibility to select the configuration of the lift system and the performance parameters of each component. In addition to the overall system response, detailed information of transients, vibrations of the lift components, ride quality levels, modal analysis and frequency spectrum (FFT) are plotted.

  13. Asymmetric responses of primary productivity to precipitation extremes: A synthesis of grassland precipitation manipulation experiments.

    Science.gov (United States)

    Wilcox, Kevin R; Shi, Zheng; Gherardi, Laureano A; Lemoine, Nathan P; Koerner, Sally E; Hoover, David L; Bork, Edward; Byrne, Kerry M; Cahill, James; Collins, Scott L; Evans, Sarah; Gilgen, Anna K; Holub, Petr; Jiang, Lifen; Knapp, Alan K; LeCain, Daniel; Liang, Junyi; Garcia-Palacios, Pablo; Peñuelas, Josep; Pockman, William T; Smith, Melinda D; Sun, Shanghua; White, Shannon R; Yahdjian, Laura; Zhu, Kai; Luo, Yiqi

    2017-10-01

    Climatic changes are altering Earth's hydrological cycle, resulting in altered precipitation amounts, increased interannual variability of precipitation, and more frequent extreme precipitation events. These trends will likely continue into the future, having substantial impacts on net primary productivity (NPP) and associated ecosystem services such as food production and carbon sequestration. Frequently, experimental manipulations of precipitation have linked altered precipitation regimes to changes in NPP. Yet, findings have been diverse and substantial uncertainty still surrounds generalities describing patterns of ecosystem sensitivity to altered precipitation. Additionally, we do not know whether previously observed correlations between NPP and precipitation remain accurate when precipitation changes become extreme. We synthesized results from 83 case studies of experimental precipitation manipulations in grasslands worldwide. We used meta-analytical techniques to search for generalities and asymmetries of aboveground NPP (ANPP) and belowground NPP (BNPP) responses to both the direction and magnitude of precipitation change. Sensitivity (i.e., productivity response standardized by the amount of precipitation change) of BNPP was similar under precipitation additions and reductions, but ANPP was more sensitive to precipitation additions than reductions; this was especially evident in drier ecosystems. Additionally, overall relationships between the magnitude of productivity responses and the magnitude of precipitation change were saturating in form. The saturating form of this relationship was likely driven by ANPP responses to very extreme precipitation increases, although there were limited studies imposing extreme precipitation change, and there was considerable variation among experiments. This highlights the importance of incorporating gradients of manipulations, ranging from extreme drought to extreme precipitation increases into future climate change

  14. An investigation and understanding of the mechanical response of Palmyrah timber

    International Nuclear Information System (INIS)

    Sobier, Hatim; Menzemer, C.C.; Srivatsan, T.S.

    2003-01-01

    The Palmyrah tree flourishes in tropical areas around South East Asia, and particularly in Sri Lanka. Palmyrah is an important economic resource for the region, and has found use in structural applications for both residential dwellings and commercial buildings. While there is a great deal of local field experience with Palmyrah, the mechanical properties have not been well characterized or understood. In an effort to assist engineers with the design and efficient use of the timber, a study was undertaken to evaluate the mechanical response of Palmyrah and develop estimates of design allowable properties. Properties evaluated include static bending strength, modulus, compression parallel and perpendicular to the grain, shear parallel to the grain and tensile strength parallel and perpendicular to the grain. In order to gain insight into the behavior of the wood, samples were examined using standard optical microscopy techniques. In addition, available fracture surfaces were examined using scanning electron microscopy

  15. UV radiation in marine ectotherms: Molecular effects and responses

    International Nuclear Information System (INIS)

    Dahms, Hans-U.; Lee, Jae-Seong

    2010-01-01

    This review summarizes current knowledge on ultraviolet radiation (UVR)-induced cellular and molecular damage in marine ectotherms (invertebrates and fish). UVR impairs sperm motility, reduces fertilization, and causes embryo malformation that in turn affects recruitment and therefore the sustainability of natural populations. The direct molecular effects of UVR are mediated by absorption of certain wavelengths by specific macromolecules and the dissipation of the absorbed energy via photochemical reactions. Most organisms have defense mechanisms that either prevent UVR-induced damage, or mechanisms that repair the damage. Photoprotective pigments, antioxidant defense compounds, and cell cycle development genes are some of the molecules involved in UVR defense. Photoenzymatic repair and nucleotide excision repair are the two primary DNA repair systems in marine ectotherms. We anticipate that toxicogenomic studies will gain importance in UVR research because they can elucidate the primary processes involved in UVR damage and the cellular response to this damage.

  16. Plant physiology meets phytopathology: plant primary metabolism and plant-pathogen interactions.

    Science.gov (United States)

    Berger, Susanne; Sinha, Alok K; Roitsch, Thomas

    2007-01-01

    Phytopathogen infection leads to changes in secondary metabolism based on the induction of defence programmes as well as to changes in primary metabolism which affect growth and development of the plant. Therefore, pathogen attack causes crop yield losses even in interactions which do not end up with disease or death of the plant. While the regulation of defence responses has been intensively studied for decades, less is known about the effects of pathogen infection on primary metabolism. Recently, interest in this research area has been growing, and aspects of photosynthesis, assimilate partitioning, and source-sink regulation in different types of plant-pathogen interactions have been investigated. Similarly, phytopathological studies take into consideration the physiological status of the infected tissues to elucidate the fine-tuned infection mechanisms. The aim of this review is to give a summary of recent advances in the mutual interrelation between primary metabolism and pathogen infection, as well as to indicate current developments in non-invasive techniques and important strategies of combining modern molecular and physiological techniques with phytopathology for future investigations.

  17. Mechanisms of efferent-mediated responses in the turtle posterior crista.

    Science.gov (United States)

    Holt, Joseph C; Lysakowski, Anna; Goldberg, Jay M

    2006-12-20

    To study the cellular mechanisms of efferent actions, we recorded from vestibular-nerve afferents close to the turtle posterior crista while efferent fibers were electrically stimulated. Efferent-mediated responses were obtained from calyx-bearing (CD, calyx and dimorphic) afferents and from bouton (B) afferents distinguished by their neuroepithelial locations into BT units near the torus and BM units at intermediate sites. The spike discharge of CD units is strongly excited by efferent stimulation, whereas BT and BM units are inhibited, with BM units also showing a postinhibitory excitation. Synaptic activity was recorded intracellularly after spikes were blocked. Responses of BT/BM units to single efferent shocks consist of a brief depolarization followed by a prolonged hyperpolarization. Both components reflect variations in hair-cell quantal release rates and are eliminated by pharmacological antagonists of alpha9/alpha10 nicotinic receptors. Blocking calcium-dependent SK potassium channels converts the biphasic response into a prolonged depolarization. Results can be explained, as in other hair-cell systems, by the sequential activation of alpha9/alpha10 and SK channels. In BM units, the postinhibitory excitation is based on an increased rate of hair-cell quanta and depends on the preceding inhibition. There is, in addition, an efferent-mediated, direct depolarization of BT/BM and CD fibers. In CD units, it is the exclusive efferent response. Nicotinic antagonists have different effects on hair-cell efferent actions and on the direct depolarization of CD and BT/BM units. Ultrastructural studies, besides confirming the efferent innervation of type II hair cells and calyx endings, show that turtle efferents commonly contact afferent boutons terminating on type II hair cells.

  18. Impact of Microbes on the Pathogenesis of Primary Biliary Cirrhosis (PBC and Primary Sclerosing Cholangitis (PSC

    Directory of Open Access Journals (Sweden)

    Jochen Mattner

    2016-11-01

    Full Text Available Primary biliary cirrhosis (PBC and primary sclerosing cholangitis (PSC represent the major clinical entities of chronic cholestatic liver diseases. Both disorders are characterized by portal inflammation and slowly progress to obliterative fibrosis and eventually liver cirrhosis. Although immune-pathogenic mechanisms have been implicated in the pathogenesis of PBC and PSC, neither disorder is considered to be a classical autoimmune disease, as PSC and PBC patients do not respond to immune-suppressants. Furthermore, the decreased bile flow resulting from the immune-mediated tissue assault and the subsequent accumulation of toxic bile products in PBC and PSC not only perpetuates biliary epithelial damage, but also alters the composition of the intestinal and biliary microbiota and its mutual interactions with the host. Consistent with the close association of PSC and inflammatory bowel disease (IBD, the polyclonal hyper IgM response in PBC and (auto-antibodies which cross-react to microbial antigens in both diseases, an expansion of individual microbes leads to shifts in the composition of the intestinal or biliary microbiota and a subsequent altered integrity of epithelial layers, promoting microbial translocation. These changes have been implicated in the pathogenesis of both devastating disorders. Thus, we will discuss here these recent findings in the context of novel and alternative therapeutic options.

  19. Microfluidic measurement of effects of ACF7/MACF1 gene on the mechanics of primary cortical neurons

    Science.gov (United States)

    Lee, Donghee; Ka, Minhan; Kim, Woo-Yang; Ryu, Sangjin

    2014-03-01

    Actin filaments and microtubules play important roles in determining the mechanics of cells, and ACF7/MACF1 (Actin Crosslinking Family 7/Microtubule And Actin Crosslinking Factor 1) gene seems to be closely related to connections between actin filaments and microtubules. To identify such roles of the ACF7/MACF1 gene of primary cortical neurons, we isolated neuronal cells from the cerebral cortex of the embryonic mouse brain, which is important in memory, language and perception. We exerted viscous shear flow to normal neuronal cells and ACF7/MACF1 gene knockout neuronal cells using rectangular microfluidic channels. While changing viscous shear stress on the cells, we recorded changes in the morphology of the two cell types using video microscopy. Having analyzed the deformation of the cells, we could quantitatively correlate differences in the morphological change between the both normal and ACF7/MACF1 gene knockout neuronal cells to the applied shear force, which will contribute toward identifying cell mechanical roles of the ACF7/MACF1 gene.

  20. Lymphocytes B and primary immunodeficiencies

    Directory of Open Access Journals (Sweden)

    Gabriela López-Herrera

    2016-03-01

    Full Text Available Primary antibody deficiencies represent the most frequent genetic diseases of the immune system and the first to be recognized along immunology history. The antibodies were recognized as part of the humoral immune system long ago, and after immunoglobulin discovery, the first antibody immunodeficiency were recognized and named as “agammaglobulinemia”, followed by the common variable immunodeficiency and the hyper-IgM syndrome. The following discoveries in immunology history made possible the understanding of these pathologies, for example: the discoveries of B cells, pre-B cells, the signaling pathway directed by the antigen receptor and many other cellular and molecular mechanisms. Primary antibody deficiencies have been studied for a long time and the discoveries of new syndromes have been helpful in the understanding of immunological mechanisms that take place in our organism. Then, this manuscript pretends to review the relevant findings in the history of immunology, focused on the B cells and the connection with the description of representative clinical entities of primary antibody deficiencies. The aim of this manuscript is to show to the reader that the generation of scientific knowledge has a direct application in the understanding of the molecular mechanisms that are affected in these diseases.

  1. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

  2. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  3. Maximising electro-mechanical response by minimising grain-scale strain heterogeneity in phase-change actuator ceramics

    DEFF Research Database (Denmark)

    Oddershede, Jette; Hossain, Mohammad Jahangir; Daniels, John E.

    2016-01-01

    Phase-change actuator ceramics directly couple electrical and mechanical energies through an electric-field-induced phase transformation. These materials are promising for the replacement of the most common electro-mechanical ceramic, lead zirconate titanate, which has environmental concerns. Here......, we show that by compositional modification, we reduce the grain-scale heterogeneity of the electro-mechanical response by 40%. In the materials investigated, this leads to an increase in the achievable electric-field-induced strain of the bulk ceramic of 45%. Compositions of (100-x)Bi0.5Na0.5TiO3-(x...... heterogeneity can be achieved by precise control of the lattice distortions and orientation distributions of the induced phases. The current results can be used to guide the design of next generation high-strain electro-mechanical ceramic actuator materials....

  4. Time course of lung inflammatory and fibrogenic responses during protective mechanical ventilation in healthy rats.

    Science.gov (United States)

    Krebs, Joerg; Pelosi, Paolo; Tsagogiorgas, Charalambos; Haas, Jenny; Yard, Benito; Rocco, Patricia R M; Luecke, Thomas

    2011-09-15

    This study aimed to assess pulmonary inflammatory and fibrogenic responses and their impact on lung mechanics and histology in healthy rats submitted to protective mechanical ventilation for different experimental periods. Eighteen Wistar rats were randomized to undergo open lung-mechanical ventilation (OL-MV) for 1, 6 or 12 h. Following a recruitment maneuver, a decremental PEEP trial was performed and PEEP set according to the minimal respiratory system static elastance. Respiratory system, lung, and chest-wall elastance and gas-exchange were maintained throughout the 12 h experimental period. Histological lung injury score remained low at 1 and 6 h, but was higher at 12 h due to overinflation. A moderate inflammatory response was observed with a distinct peak at 6h. Compared to unventilated controls, type I procollagen mRNA expression was decreased at 1 and 12h, while type III procollagen expression decreased throughout the 12h experimental period. In conclusion, OL-MV in healthy rats yielded overinflation after 6 h even though respiratory elastance and gas-exchange were preserved for up to 12 h. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Engine Tune-Up Service. Unit 3: Primary Circuit. Posttests. Automotive Mechanics Curriculum.

    Science.gov (United States)

    Morse, David T.

    This book of posttests is designed to accompany the Engine Tune-Up Service Student Guide for Unit 3, Primary Circuit, available separately as CE 031 211. Focus of the posttests is setting the primary ignition circuit. One multiple choice posttest is provided, covering the eight performance objectives contained in the unit. (No answer key is…

  6. Maize Stem Response to Long-Term Attack by Sesamia nonagrioides

    Directory of Open Access Journals (Sweden)

    Victor M. Rodriguez

    2018-04-01

    Full Text Available Plants defend themselves against herbivores by activating a plethora of genetic and biochemical mechanisms aimed at reducing plant damage and insect survival. The short-term plant response to insect attack is well understood, but less is known about the maintenance of this response over time. We performed transcriptomic and metabolomics analyses in order to identify genes and metabolites involved in the long-term response of maize to attack by the corn borer Sesamina nonagrioides. To determine the role of elicitors present in caterpillar secretions, we also evaluated the response of maize stem challenged with insect regurgitates. The integrative analysis of the omics results revealed that the long-term response in maize is characterized by repression of the primary metabolism and a strong redox response, mainly mediated by germin-like proteins to produce anti-nutritive and toxic compounds that reduce insect viability, and with the glutathione–ascorbate cycle being crucial to minimize the adverse effects of reactive oxygen species (ROS on the plant. Our results suggest that different defense mechanisms are involved in the long-term response compared to those reported during the early response. We also observed a marginal effect of the caterpillar regurgitates on the long-term defensive response.

  7. Lasers in primary open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Sihota Ramanjit

    2011-12-01

    Full Text Available Lasers have been used in the treatment of primary open angle glaucoma (POAG over the years, with the hope that they would eventually replace medical and surgical therapy. Laser trabeculoplasty (LT is an application of argon, diode, or selective laser energy to the surface of the trabecular meshwork to increase the aqueous outflow. The mechanisms by which intraocular pressure (IOP is lowered could be mechanical, biologic, or by division of adjacent cells. It is commonly used as an adjunct to medical therapy, but is contraindicated if the angle is obstructed, e.g., peripheral anterior synechia (PAS or developmental glaucomas. About 75% of individuals will show a significant fall in IOP after argon laser trabeculoplasty (ALT, and the response is similar with selective laser trabeculoplasty (SLT. The effects of LT are not always long lasting, with about 10% of individuals showing a rise in IOP with every passing year. Laser thermal sclerostomy, ab interno or externo, is an alternative to other full-thickness filtration procedures. Longer wavelengths in the infrared range have water-absorptive characteristics that facilitate perforation of the sclera. These lasers can be used to avoid intraocular instrumentation and minimize conjunctival trauma.

  8. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies.

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M

    2014-07-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitary-adrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the formation of

  9. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies

    Science.gov (United States)

    Finsterwald, Charles; Alberini, Cristina M.

    2013-01-01

    A proper response against stressors is critical for survival. In mammals, the stress response is primarily mediated by secretion of glucocorticoids via the hypothalamic-pituitaryadrenocortical (HPA) axis and release of catecholamines through adrenergic neurotransmission. Activation of these pathways results in a quick physical response to the stress and, in adaptive conditions, mediates long-term changes in the brain that lead to the formation of long-term memories of the experience. These long-term memories are an essential adaptive mechanism that allows an animal to effectively face similar demands again. Indeed, a moderate stress level has a strong positive effect on memory and cognition, as a single arousing or moderately stressful event can be remembered for up to a lifetime. Conversely, exposure to extreme, traumatic, or chronic stress can have the opposite effect and cause memory loss, cognitive impairments, and stress-related psychopathologies such as anxiety disorders, depression and post-traumatic stress disorder (PTSD). While more effort has been devoted to the understanding of the effects of the negative effects of chronic stress, much less has been done thus far on the identification of the mechanisms engaged in the brain when stress promotes long-term memory formation. Understanding these mechanisms will provide critical information for use in ameliorating memory processes in both normal and pathological conditions. Here, we will review the role of glucocorticoids and glucocorticoid receptors (GRs) in memory formation and modulation. Furthermore, we will discuss recent findings on the molecular cascade of events underlying the effect of GR activation in adaptive levels of stress that leads to strong, long-lasting memories. Our recent data indicate that the positive effects of GR activation on memory consolidation critically engage the brain-derived neurotrophic factor (BDNF) pathway. We propose and will discuss the hypothesis that stress promotes the

  10. Gravity response mechanisms of lateral organs and the control of plant architecture in Arabidopsis

    Science.gov (United States)

    Mullen, J.; Hangarter, R.

    Most research on gravity responses in plants has focused on primary roots and shoots, which typically grow in a vertical orientation. However, the patterns of lateral organ formation and their growth orientation, which typically are not vertical, govern plant architecture. For example, in Arabidopsis, when lateral roots emerge from the primary root, they grow at a nearly horizontal orientation. As they elongate, the roots slowly curve until they eventually reach a vertical orientation. The regulation of this lateral root orientation is an important component affecting the overall root system architecture. We have found that this change in orientation is not simply due to the onset of gravitropic competence, as non-vertical lateral roots are capable of both positive and negative gravitropism. Thus, the horizontal growth of the new lateral roots is determined by what is called the gravitropic set-point angle (GSA). In Arabidopsis shoots, rosette leaves and inflorescence branches also display GSA-dependent developmental changes in their orientation. The developmental control of the GSA of lateral organs in Arabidopsis provides us with a useful system for investigating the components involved in regulating directionality of tropistic responses. We have identified several Arabidopsis mutants that have either altered lateral root orientations, altered orientation of lateral organs in the shoot, or both, but maintain normal primary organ orientation. The mgsa ({m}odified {g}ravitropic {s}et-point {a}ngle) mutants with both altered lateral root and shoot orientation show that there are common components in the regulation of growth orientation in the different organs. Rosette leaves and lateral roots also have in common a regulation of positioning by red light. Further molecular and physiological analyses of the GSA mutants will provide insight into the basis of GSA regulation and, thus, a better understanding of how gravity controls plant architecture. [This work was

  11. Critiquing the response to the Ebola epidemic through a Primary Health Care Approach.

    Science.gov (United States)

    Scott, Vera; Crawford-Browne, Sarah; Sanders, David

    2016-05-17

    The 2014/2015 West Africa Ebola epidemic has caused the global public health community to engage in difficult self-reflection. First, it must consider the part it played in relation to an important public health question: why did this epidemic take hold and spread in this unprecedented manner? Second, it must use the lessons learnt to answer the subsequent question: what can be done now to prevent further such outbreaks in the future? These questions remain relevant, even as scientists announce that the Guinea Phase III efficacy vaccine trial shows that rVSV-EBOV (Merck, Sharp & Dohme) is highly efficacious in individuals. This is a major breakthrough in the fight against Ebola virus disease (EVD). It does not replace but may be a powerful adjunct to current strategies of EVD management and control. We contribute to the current self-reflection by presenting an analysis using a Primary Health Care (PHC) approach. This approach is appropriate as African countries in the region affected by EVD have recommitted themselves to PHC as a framework for organising health systems and the delivery of health services. The approach suggests that, in an epidemic made complex by weak pre-existing health systems, lack of trust in authorities and mobile populations, a broader approach is required to engage affected communities. In the medium-term health system development with attention to primary level services and community-based programmes to address the major disease burden of malaria, diarrhoeal disease, meningitis, tuberculosis and malnutrition is needed. This requires the development of local management and an investment in human resources for health. Crucially this has to be developed ahead of, and not in parallel with, future outbreaks. In the longer-term a commitment is required to address the underlying social determinants which make these countries so vulnerable, and limit their capacity to respond effectively to, epidemics such as EVD. The PHC approach offers an

  12. Critiquing the response to the Ebola epidemic through a Primary Health Care Approach

    Directory of Open Access Journals (Sweden)

    Vera Scott

    2016-05-01

    Full Text Available Abstract Background The 2014/2015 West Africa Ebola epidemic has caused the global public health community to engage in difficult self-reflection. First, it must consider the part it played in relation to an important public health question: why did this epidemic take hold and spread in this unprecedented manner? Second, it must use the lessons learnt to answer the subsequent question: what can be done now to prevent further such outbreaks in the future? These questions remain relevant, even as scientists announce that the Guinea Phase III efficacy vaccine trial shows that rVSV-EBOV (Merck, Sharp & Dohme is highly efficacious in individuals. This is a major breakthrough in the fight against Ebola virus disease (EVD. It does not replace but may be a powerful adjunct to current strategies of EVD management and control. Discussion We contribute to the current self-reflection by presenting an analysis using a Primary Health Care (PHC approach. This approach is appropriate as African countries in the region affected by EVD have recommitted themselves to PHC as a framework for organising health systems and the delivery of health services. The approach suggests that, in an epidemic made complex by weak pre-existing health systems, lack of trust in authorities and mobile populations, a broader approach is required to engage affected communities. In the medium-term health system development with attention to primary level services and community-based programmes to address the major disease burden of malaria, diarrhoeal disease, meningitis, tuberculosis and malnutrition is needed. This requires the development of local management and an investment in human resources for health. Crucially this has to be developed ahead of, and not in parallel with, future outbreaks. In the longer-term a commitment is required to address the underlying social determinants which make these countries so vulnerable, and limit their capacity to respond effectively to, epidemics

  13. Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki [Shimane Medical Univ., Izumo (Japan)

    1998-03-01

    Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

  14. Neoadjuvant radiotherapy for primary advanced or locally recurrent breast cancer

    International Nuclear Information System (INIS)

    Watanabe, Hiroaki; Nio, Yoshinori; Inoue, Yasushi; Teramoto, Mutsumi; Nagami, Haruhiko; Yano, Seiji; Sumi, Shoichiro; Tamura, Katsuhiro; Kushima, Takeyuki

    1998-01-01

    Neoadjuvant radiotherapy for breast cancer has rarely been reported. In the present study, we investigated the objective response and histopathological effects of neoadjuvant radiotherapy in patients with primary advanced or locally recurrent breast cancer. Between 1992 and 1997, a total of 11 patients with primary or recurrent breast cancer (5 primary advanced and 6 locally recurrent breast cancers) were treated with neoadjuvant radiotherapy before surgery. Six patients received radiotherapy alone and 5 received radiotherapy in combination with chemotherapy, and the objective response was assessed according to the criteria of the Japanese Society of Cancer Therapy. After neoadjuvant radiotherapy or radiochemotherapy, all patients underwent surgery or biopsy, and histopathological effects were assessed according to the criteria of the Japanese Research Society for Gastric Cancer Study. The overall objective response was 27% (3PR/11; 2PR in 5 primary cancers and 1PR in 6 recurrent cancers), and histopathological effects included 5 grade-3 or -2 responses (45%; 2 grade-3 and 1 grade-2 in primary cancers and 2 grade-2 in recurrent cancers). There were no correlations between total radiation dose and objective response or histopathological effects. The objective response rates were 40% (2/5) in the radiochemotherapy group and 17% (1/6) in the radiotherapy alone group, histopathological effects higher than grade-2 were seen in 60% (3/5) in the radiochemotherapy group and 33% (2/6) in the radiotherapy alone group, and a grade-3 response was seen only in the radiochemotherapy group. Neoadjuvant radiotherapy for breast cancer resulted in a high response rate and was more effective against primary cancer than recurrent cancer. Furthermore, chemotherapy may be beneficial in improving the efficacy of radiotherapy. (author)

  15. Adaptive Response in Animals Exposed to Non-Ionizing Radiofrequency Fields: Some Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Yi Cao

    2014-04-01

    Full Text Available During the last few years, our research group has been investigating the phenomenon of adaptive response in animals exposed to non-ionizing radiofrequency fields. The results from several separate studies indicated a significant increase in survival, decreases in genetic damage as well as oxidative damage and, alterations in several cellular processes in mice pre-exposed to radiofrequency fields and subsequently subjected to sub-lethal or lethal doses of γ-radiation or injected with bleomycin, a radiomimetic chemical mutagen. These observations indicated the induction of adaptive response providing the animals the ability to resist subsequent damage. Similar studies conducted by independent researchers in mice and rats have supported our observation on increased survival. In this paper, we have presented a brief review of all of our own and other independent investigations on radiofrequency fields-induced adaptive response and some underlying mechanisms discussed.

  16. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G

    2000-01-01

    Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...... on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...

  17. ICECO-CEL: a coupled Eulerian-Lagrangian code for analyzing primary system response in fast reactors

    International Nuclear Information System (INIS)

    Wang, C.Y.

    1981-02-01

    This report describes a coupled Eulerian-Lagrangian code, ICECO-CEL, for analyzing the response of the primary system during hypothetical core disruptive accidents. The implicit Eulerian method is used to calculate the fluid motion so that large fluid distortion, two-dimensional sliding interface, flow around corners, flow through coolant passageways, and out-flow boundary conditions can be treated. The explicit Lagrangian formulation is employed to compute the response of the containment vessel and other elastic-plastic solids inside the reactor containment. Large displacements, as well as geometrical and material nonlinearities are considered in the analysis. Marker particles are utilized to define the free surface or the material interface and to visualize the fluid motion. The basic equations and numerical techniques used in the Eulerian hydrodynamics and Lagrangian structural dynamics are described. Treatment of the above-core hydrodynamics, sodium spillage, fluid cavitation, free-surface boundary conditions and heat transfer are also presented. Examples are given to illustrate the capabilities of the computer code. Comparisons of the code predictions with available experimental data are also made

  18. Effects of cortisol on the primary response of mouse spleen cell cultures to heterologous erythrocytes

    International Nuclear Information System (INIS)

    Dracott, B.N.

    1974-01-01

    Cell viability and the production of direct PFC were studied in mouse spleen cell cultures after cortisol treatment in vivo or in vitro at various times relative to primary stimulation with SRBC in vitro. Cortisol treatment in vivo reduced spleen cell numbers by 88 percent after 48 hr, but cultures of the remaining cells produced as many PFC in vitro as did cultures of equal numbers of normal spleen cells. In normal spleen cell cultures incubated with cortisol for 4 hr prior to the addition of antigen, peak responses of PFC/culture and PFC/10 6 cells occurred 24 hr later than in controls and averaged, respectively, 27 and 141 percent of control values. Minimum viable cell numbers were observed in cortisol-treated cultures after 3 days; thereafter cell numbers gradually increased. These results were not significantly altered when cultures were treated simultaneously with cortisol and antigen. The response was not suppressed if the addition of antigen preceded that of cortisol by more than 4 hr. Suppression was also considerably reduced if fetal calf serum was used when preparing cells for culture

  19. Activation of Proinflammatory Responses in Cells of the Airway Mucosa by Particulate Matter: Oxidant- and Non-Oxidant-Mediated Triggering Mechanisms

    Directory of Open Access Journals (Sweden)

    Johan Øvrevik

    2015-07-01

    Full Text Available Inflammation is considered to play a central role in a diverse range of disease outcomes associated with exposure to various types of inhalable particulates. The initial mechanisms through which particles trigger cellular responses leading to activation of inflammatory responses are crucial to clarify in order to understand what physico-chemical characteristics govern the inflammogenic activity of particulate matter and why some particles are more harmful than others. Recent research suggests that molecular triggering mechanisms involved in activation of proinflammatory genes and onset of inflammatory reactions by particles or soluble particle components can be categorized into direct formation of reactive oxygen species (ROS with subsequent oxidative stress, interaction with the lipid layer of cellular membranes, activation of cell surface receptors, and direct interactions with intracellular molecular targets. The present review focuses on the immediate effects and responses in cells exposed to particles and central down-stream signaling mechanisms involved in regulation of proinflammatory genes, with special emphasis on the role of oxidant and non-oxidant triggering mechanisms. Importantly, ROS act as a central second-messenger in a variety of signaling pathways. Even non-oxidant mediated triggering mechanisms are therefore also likely to activate downstream redox-regulated events.

  20. CD79B limits response of diffuse large B cell lymphoma to ibrutinib.

    Science.gov (United States)

    Kim, Joo Hyun; Kim, Won Seog; Ryu, Kyungju; Kim, Seok Jin; Park, Chaehwa

    2016-01-01

    Blockage of B cell receptor signaling with ibrutinib presents a promising clinical approach for treatment of B-cell malignancies. However, many patients show primary resistance to the drug or develop secondary resistance. In the current study, cDNA microarray and Western blot analyses revealed CD79B upregulation in the activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL) that display differential resistance to ibrutinib. CD79B overexpression was sufficient to induce resistance to ibrutinib and enhanced AKT and MAPK activation, indicative of an alternative mechanism underlying resistance. Conversely, depletion of CD79B sensitized primary refractory cells to ibrutinib and led to reduced phosphorylation of AKT or MAPK. Combination of the AKT inhibitor or the MAPK inhibitor with ibrutinib resulted in circumvention of both primary and acquired resistance in ABC-DLBCL. Our data collectively indicate that CD79B overexpression leading to activation of AKT/MAPK is a potential mechanism underlying primary ibrutinib resistance in ABC-DLBCL, and support its utility as an effective biomarker to predict therapeutic response to ibrutinib.

  1. The molecular mechanisms of plant plasma membrane intrinsic proteins trafficking and stress response.

    Science.gov (United States)

    Wang, Xing; Zhang, Ji-long; Feng, Xiu-xiu; Li, Hong-jie; Zhang, Gen-fa

    2017-04-20

    Plasma membrane intrinsic proteins (PIPs) are plant channel proteins located on the plasma membrane. PIPs transfer water, CO 2 and small uncharged solutes through the plasma membrane. PIPs have high selectivity to substrates, suggestive of a central role in maintaining cellular water balance. The expression, activity and localization of PIPs are regulated at the transcriptional and post-translational levels, and also affected by environmental factors. Numerous studies indicate that the expression patterns and localizations of PIPs can change in response to abiotic stresses. In this review, we summarize the mechanisms of PIP trafficking, transcriptional and post-translational regulations, and abiotic stress responses. Moreover, we also discuss the current research trends and future directions on PIPs.

  2. Dissection of Ire1 functions reveals stress response mechanisms uniquely evolved in Candida glabrata.

    Directory of Open Access Journals (Sweden)

    Taiga Miyazaki

    2013-01-01

    Full Text Available Proper protein folding in the endoplasmic reticulum (ER is vital in all eukaryotes. When misfolded proteins accumulate in the ER lumen, the transmembrane kinase/endoribonuclease Ire1 initiates splicing of HAC1 mRNA to generate the bZIP transcription factor Hac1, which subsequently activates its target genes to increase the protein-folding capacity of the ER. This cellular machinery, called the unfolded protein response (UPR, is believed to be an evolutionarily conserved mechanism in eukaryotes. In this study, we comprehensively characterized mutant phenotypes of IRE1 and other related genes in the human fungal pathogen Candida glabrata. Unexpectedly, Ire1 was required for the ER stress response independently of Hac1 in this fungus. C. glabrata Ire1 did not cleave mRNAs encoding Hac1 and other bZIP transcription factors identified in the C. glabrata genome. Microarray analysis revealed that the transcriptional response to ER stress is not mediated by Ire1, but instead is dependent largely on calcineurin signaling and partially on the Slt2 MAPK pathway. The loss of Ire1 alone did not confer increased antifungal susceptibility in C. glabrata contrary to UPR-defective mutants in other fungi. Taken together, our results suggest that the canonical Ire1-Hac1 UPR is not conserved in C. glabrata. It is known in metazoans that active Ire1 nonspecifically cleaves and degrades a subset of ER-localized mRNAs to reduce the ER load. Intriguingly, this cellular response could occur in an Ire1 nuclease-dependent fashion in C. glabrata. We also uncovered the attenuated virulence of the C. glabrata Δire1 mutant in a mouse model of disseminated candidiasis. This study has unveiled the unique evolution of ER stress response mechanisms in C. glabrata.

  3. Mechanical properties and shape memory effect of thermal-responsive polymer based on PVA

    Science.gov (United States)

    Lin, Liulan; Zhang, Lingfeng; Guo, Yanwei

    2018-01-01

    In this study, the effect of content of glutaraldehyde (GA) on the shape memory behavior of a shape memory polymer based on polyvinyl alcohol chemically cross-linked with GA was investigated. Thermal-responsive shape memory composites with three different GA levels, GA-PVA (3 wt%, 5 wt%, 7 wt%), were prepared by particle melting, mold forming and freeze-drying technique. The mechanical properties, thermal properties and shape memory behavior were measured by differential scanning calorimeter, physical bending test and cyclic thermo-mechanical test. The addition of GA to PVA led to a steady shape memory transition temperature and an improved mechanical compressive strength. The composite with 5 wt% of GA exhibited the best shape recoverability. Further increase in the crosslinking agent content of GA would reduce the recovery force and prolong the recovery time due to restriction in the movement of the soft PVA chain segments. These results provide important information for the study on materials in 4D printing.

  4. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

    Energy Technology Data Exchange (ETDEWEB)

    Kadhim, Munira A

    2012-08-22

    The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program. To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e. less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these "non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate non-targeted effects of ionizing radiation with a focus on the induction of genomic instability (GI) in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/CaH and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition in these models on genomic instability. We will specifically focus on the effects of low doses of low LET radiation, down to the dose of 10mGy (0.01Gy) X-rays. Using conventional X-ray and we will be able to assess the role of genetic variation under various conditions at a range of doses down to the very low dose of 0.01Gy. Irradiations will be carried out using facilities in routine operation for such studies. Mechanistic studies of instability in different cell

  5. On chaos in quantum mechanics: The two meanings of sensitive dependence

    International Nuclear Information System (INIS)

    Ingraham, R.L.; Luna Acosta, G.A.

    1993-08-01

    Sensitive dependence on initial conditions, the most important signature of chaos, can mean failure of Lyapunov stability, the primary meaning adopted in dynamical systems theory, or the presence of positive Lyapunov exponents, the meaning favored in physics. These are not equivalent in general. We show that there is sensitive dependence in quantum mechanics in the sense of violation of Lyapunov stability for maps of the state vector like involving unbounded operators A. This is true even for bounded quantum systems, where the corresponding Lyapunov exponents are all zero. Experiments to reveal this sensitive dependence, a definite though unfamiliar prediction of quantum mechanics, should be devised. It may also invalidate the usual assumption of linear response theory in quantum statistical mechanics in some cases. (author) 13 refs

  6. CD11c controls herpes simplex virus 1 responses to limit virus replication during primary infection.

    Science.gov (United States)

    Allen, Sariah J; Mott, Kevin R; Chentoufi, Aziz A; BenMohamed, Lbachir; Wechsler, Steven L; Ballantyne, Christie M; Ghiasi, Homayon

    2011-10-01

    CD11c is expressed on the surface of dendritic cells (DCs) and is one of the main markers for identification of DCs. DCs are the effectors of central innate immune responses, but they also affect acquired immune responses to infection. However, how DCs influence the efficacy of adaptive immunity is poorly understood. Here, we show that CD11c(+) DCs negatively orchestrate both adaptive and innate immunity against herpes simplex virus type 1 (HSV-1) ocular infection. The effectiveness and quantity of virus-specific CD8(+) T cell responses are increased in CD11c-deficient animals. In addition, the levels of CD83, CD11b, alpha interferon (IFN-α), and IFN-β, but not IFN-γ, were significantly increased in CD11c-deficient animals. Higher levels of IFN-α, IFN-β, and CD8(+) T cells in the CD11c-deficient mice may have contributed to lower virus replication in the eye and trigeminal ganglia (TG) during the early period of infection than in wild-type mice. However, the absence of CD11c did not influence survival, severity of eye disease, or latency. Our studies provide for the first time evidence that CD11c expression may abrogate the ability to reduce primary virus replication in the eye and TG via higher activities of type 1 interferon and CD8(+) T cell responses.

  7. Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis.

    Directory of Open Access Journals (Sweden)

    Scott Kilpatrick

    Full Text Available Primary hepatopathies are a common cause of morbidity and mortality in dogs. The underlying aetiology of most cases of canine hepatitis is unknown. Consequently, treatments are typically palliative and it is difficult to provide accurate prognostic information to owners. In human hepatology there is accumulating data which indicates that the presence of systemic inflammatory response syndrome (SIRS is a common and debilitating event in patients with liver diseases. For example, the presence of SIRS has been linked to the development of complications such as hepatic encephalopathy (HE and is associated with a poor clinical outcome in humans with liver diseases. In contrast, the relationship between SIRS and clinical outcome in dogs with a primary hepatitis is unknown. Seventy dogs with histologically confirmed primary hepatitis were enrolled into the study. Additional clinical and clinicopathological information including respiratory rate, heart rate, temperature, white blood cell count, sodium, potassium, sex, presence of ascites, HE score, alanine aminotransferase (ALT, alkaline phosphatase (ALP, bilirubin and red blood cell concentration were available in all cases. The median survival of dogs with a SIRS score of 0 or 1 (SIRS low was 231 days compared to a median survival of 7 days for dogs with a SIRS score of 2, 3 or 4 (SIRS high (p<0.001. A Cox proportional hazard model, which included all other co-variables, revealed that a SIRS high score was an independent predictor of a poor clinical outcome. The effect of modulating inflammation on treatment outcomes in dogs with a primary hepatitis is deserving of further study.

  8. Short- and long-term behavioural, physiological and stoichiometric responses to predation risk indicate chronic stress and compensatory mechanisms.

    Science.gov (United States)

    Van Dievel, Marie; Janssens, Lizanne; Stoks, Robby

    2016-06-01

    Prey organisms are expected to use different short- and long-term responses to predation risk to avoid excessive costs. Contrasting both types of responses is important to identify chronic stress responses and possible compensatory mechanisms in order to better understand the full impact of predators on prey life history and population dynamics. Using larvae of the damselfly Enallagma cyathigerum, we contrasted the effects of short- and long-term predation risk, with special focus on consequences for body stoichiometry. Under short-term predation risk, larvae reduced growth rate, which was associated with a reduced food intake, increased metabolic rate and reduced glucose content. Under long-term predation risk, larvae showed chronic predator stress as indicated by persistent increases in metabolic rate and reduced food intake. Despite this, larvae were able to compensate for the short-term growth reduction under long-term predation risk by relying on physiological compensatory mechanisms, including reduced energy storage. Only under long-term predation risk did we observe an increase in body C:N ratio, as predicted under the general stress paradigm (GSP). Although this was caused by a predator-induced decrease in N content, there was no associated increase in C content. These stoichiometric changes could not be explained by GSP responses because, under chronic predation risk, there was no decrease in N-rich proteins or increase in C-rich fat and sugars; instead glycogen decreased. Our results highlight the importance of compensatory mechanisms and the value of explicitly integrating physiological mechanisms to obtain insights into the temporal dynamics of non-consumptive effects, including effects on body stoichiometry.

  9. The Coda of the Transient Response in a Sensitive Cochlea: A Computational Modeling Study.

    Directory of Open Access Journals (Sweden)

    Yizeng Li

    2016-07-01

    Full Text Available In a sensitive cochlea, the basilar membrane response to transient excitation of any kind-normal acoustic or artificial intracochlear excitation-consists of not only a primary impulse but also a coda of delayed secondary responses with varying amplitudes but similar spectral content around the characteristic frequency of the measurement location. The coda, sometimes referred to as echoes or ringing, has been described as a form of local, short term memory which may influence the ability of the auditory system to detect gaps in an acoustic stimulus such as speech. Depending on the individual cochlea, the temporal gap between the primary impulse and the following coda ranges from once to thrice the group delay of the primary impulse (the group delay of the primary impulse is on the order of a few hundred microseconds. The coda is physiologically vulnerable, disappearing when the cochlea is compromised even slightly. The multicomponent sensitive response is not yet completely understood. We use a physiologically-based, mathematical model to investigate (i the generation of the primary impulse response and the dependence of the group delay on the various stimulation methods, (ii the effect of spatial perturbations in the properties of mechanically sensitive ion channels on the generation and separation of delayed secondary responses. The model suggests that the presence of the secondary responses depends on the wavenumber content of a perturbation and the activity level of the cochlea. In addition, the model shows that the varying temporal gaps between adjacent coda seen in experiments depend on the individual profiles of perturbations. Implications for non-invasive cochlear diagnosis are also discussed.

  10. Mechanical response of jointed granite during shaft sinking at the Canadian Underground Research Laboratory

    International Nuclear Information System (INIS)

    Chan, T.; Lang, P.A.; Thompson, P.M.

    1985-01-01

    As part of the geoscience research within the Canadian Nuclear Fuel Waste Management Program, Atomic Energy of Canada Limited (AECL) is constructing an underground research laboratory (URL) in a previously undisturbed portion of a granitic intrusive, the Lac du Bonnet batholith, approximately 100 km northeast of Winnipeg, Manitoba. The overall geotechnical objectives of the URL are to assess and improve our ability to interpret and predict the geological, geophysical, geochemical, geomechanical and hydrogeological conditions of large bodies of plutonic rock, as well as to assess the accuracy of mathematical models used to predict the near-field mechanical and hydrogeological responses of the rock mass to excavation and thermal loading. Construction will be completed in July, 1986. Large-scale testing will commence soon afterwards and will last until the facility is decommissioned in the year 2000. A rectangular access shaft, 255 m deep x 2.8 m x 4.8 m, was sunk during the period May 1984 to March 1985. Rock displacements and stress changes were monitored as the excavation face (bottom) of the shaft advanced. The major objectives of this monitoring were (a) to evaluate and improve the ability of numerical models in predicting the mechanical response of the rock mass, (b) to back-calculate the rock-mass deformation modulus as a function of depth, (c) to assess the influence of natural fractures on the mechanical response of the granitic rock mass, and (d) to evaluate the quality of the geomechanical instrumentation, to determine instrumentation needs for future field experiments. Analysis of the data from this monitoring will aid the design and modelling of further experiments in the URL. In this paper, the rock displacements measured by an array of extensometers at 15 m below ground surface are presented and compared with predictions by a three-dimensional elastic continuum finite-element model

  11. Low dose irradiation does not stimulate in vivo primary antibody response in specific-pathogen-free mice

    International Nuclear Information System (INIS)

    Kamisaku, H.; Sado, T.; Muto, M.; Pongpiachan, P.; Magnemi, U.

    1991-01-01

    Recent studies from other laboratories indicated that exposure of mice to low dose radiation resulted in the enhancement of primary anti-SRBC PFC response in mice. We have repeated these experiments using four strains of mice that are known to differ in radiosensitivity of immune response potential in vivo. In one study mice were exposed to 2.5-25 cGy of X-rays. Nine hours later they were injected with SRBC and the number of PFCs per spleen was assessed individually at 4.5 days. The results indicated no evidence for the enhancement of PFC response at all exposure levels examined. In another study, groups of C57BL/6J mice were immunized with SRBC and exposed to 0, 150, or 300 cGy of X-rays 2 days later. Numbers of direct as well as indirect PFCs per spleen were then assessed individually at frequent intervals thereafter. The results indicated that exposure of mice to 150 cGy resulted in a significant increase in the number of indirect PFCs assessed at day 11 after SRBC injection, or 9 days after radiation exposure. Dose-response analysis of radiation-induced enhancement of indirect PFC response by this protocol indicated that only after exposure to 150 and 300 cGy for C57BL/6 and C3H/He strain, respectively, a significant enhancement of indirect PFC response was demonstrated. Flow cytometric analysis of spleen cells from these animals indicated that CD4+/CD+ cell ratios increased rapidly during the first three days after radiation exposure, followed by a rapid decline, suggesting that relative proportion of helper/inducer as compared to cytotoxic/suppressor T cell subset changed rapidly in favor of the former shortly after radiation exposure and possibly contributed to the observed enhancement of indirect PFC response. (author)

  12. Mechanical ventilation during extracorporeal membrane oxygenation. An international survey.

    Science.gov (United States)

    Marhong, Jonathan D; Telesnicki, Teagan; Munshi, Laveena; Del Sorbo, Lorenzo; Detsky, Michael; Fan, Eddy

    2014-07-01

    In patients with severe, acute respiratory failure undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO), the optimal strategy for mechanical ventilation is unclear. Our objective was to describe ventilation practices used in centers registered with the Extracorporeal Life Support Organization (ELSO). We conducted an international cross-sectional survey of medical directors and ECMO program coordinators from all ELSO-registered centers. The survey was distributed using a commercial website that collected information on center characteristics, the presence of a mechanical ventilator protocol, ventilator settings, and weaning practices. E-mails were sent out to medical directors or coordinators at each ELSO center and their responses were pooled for analysis. We analyzed 141 (50%) individual responses from the 283 centers contacted across 28 countries. Only 27% of centers reported having an explicit mechanical ventilation protocol for ECMO patients. The majority of these centers (77%) reported "lung rest" to be the primary goal of mechanical ventilation, whereas 9% reported "lung recruitment" to be their ventilation strategy. A tidal volume of 6 ml/kg or less was targeted by 76% of respondents, and 58% targeted a positive end-expiratory pressure of 6-10 cm H2O while ventilating patients on VV-ECMO. Centers prioritized weaning VV-ECMO before mechanical ventilation. Although ventilation practices in patients supported by VV-ECMO vary across ELSO centers internationally, the majority of centers used a strategy that targeted lung-protective thresholds and prioritized weaning VV-ECMO over mechanical ventilation.

  13. Multiscalar black holes with contingent primary hair: Mechanics and stability

    International Nuclear Information System (INIS)

    Mignemi, Salvatore; Wiltshire, David L.

    2004-01-01

    We generalize a class of magnetically charged black holes nonminimally coupled to two scalar fields previously found by one of us to the case of multiple scalar fields. The black holes possess a novel type of primary scalar hair, which we call a contingent primary hair: although the solutions possess degrees of freedom which are not completely determined by the other charges of the theory, the charges necessarily vanish in the absence of the magnetic monopole. Only one constraint relates the black hole mass to the magnetic charge and scalar charges of the theory. We obtain a Smarr-type thermodynamic relation, and the first law of black hole thermodynamics for the system. We further explicitly show in the two-scalar-field case that, contrary to the case of many other hairy black holes, the black hole solutions are stable to radial perturbations

  14. Influence of hydrazine primary water chemistry on corrosion of fuel cladding and primary circuit components

    International Nuclear Information System (INIS)

    Iourmanov, V.; Pashevich, V.; Bogancs, J.; Tilky, P.; Schunk, J.; Pinter, T.

    1999-01-01

    Earlier at Paks 1-4 NPP standard ammonia chemistry was in use. The following station performance indicators were improved when hydrazine primary water chemistry was introduced: occupational radiation exposures of personnel; gamma-radiation dose rates near primary system components during refuelling and maintenance outages. The reduction of radiation exposures and radiation fields were achieved without significant expenses. Recent results of experimental studies allowed to explain the mechanism of hydrazine dosing influence on: corrosion rate of structure materials in primary coolant; behaviour of soluble and insoluble corrosion products including long-life corrosion-induced radionuclides in primary system during steady-state and transient operation modes; radiolytic generation of oxidising radiolytic products in core and its corrosion activity in primary system; radiation situation during refuelling and maintenance outages; foreign material degradation and removal (including corrosion active oxidant species) from primary system during abnormal events. Operational experience and experimental data have shown that hydrazine primary water chemistry allows to reduce corrosion wear and thereby makes it possible to extend the life-time of plant components in primary system. (author)

  15. A study of eukaryotic response mechanisms to atmospheric pressure cold plasma by using Saccharomyces cerevisiae single gene mutants

    International Nuclear Information System (INIS)

    Feng Hongqing; Wang Ruixue; Sun Peng; Wu Haiyan; Liu Qi; Li Fangting; Fang Jing; Zhang Jue; Zhu Weidong

    2010-01-01

    The mechanisms of eukaryotic cell response to cold plasma are studied. A series of single gene mutants of eukaryotic model organism Saccharomyces cerevisiae are used to compare their sensitivity to plasma treatment with the wild type. We examined 12 mutants in the oxidative stress pathway and the cell cycle pathway, in which 8 are found to be hypersensitive to plasma processing. The mutated genes' roles in the two pathways are analyzed to understand the biological response mechanisms of plasma treatment. The results demonstrate that genes from both pathways are needed for the eukaryotic cells to survive the complex plasma treatment.

  16. Fast coding of orientation in primary visual cortex.

    Directory of Open Access Journals (Sweden)

    Oren Shriki

    Full Text Available Understanding how populations of neurons encode sensory information is a major goal of systems neuroscience. Attempts to answer this question have focused on responses measured over several hundred milliseconds, a duration much longer than that frequently used by animals to make decisions about the environment. How reliably sensory information is encoded on briefer time scales, and how best to extract this information, is unknown. Although it has been proposed that neuronal response latency provides a major cue for fast decisions in the visual system, this hypothesis has not been tested systematically and in a quantitative manner. Here we use a simple 'race to threshold' readout mechanism to quantify the information content of spike time latency of primary visual (V1 cortical cells to stimulus orientation. We find that many V1 cells show pronounced tuning of their spike latency to stimulus orientation and that almost as much information can be extracted from spike latencies as from firing rates measured over much longer durations. To extract this information, stimulus onset must be estimated accurately. We show that the responses of cells with weak tuning of spike latency can provide a reliable onset detector. We find that spike latency information can be pooled from a large neuronal population, provided that the decision threshold is scaled linearly with the population size, yielding a processing time of the order of a few tens of milliseconds. Our results provide a novel mechanism for extracting information from neuronal populations over the very brief time scales in which behavioral judgments must sometimes be made.

  17. 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

  18. THE EFFECT OF CORPORATE GOVERNANCE MECHANISM, OWNERSHIP STRUCTURE, AND EXTERNAL AUDITOR TOWARD CORPORATE SOCIAL RESPONSIBILITY DISCLOSURE WITH EARNING MANAGEMENT AS MODERATING VARIABLE

    Directory of Open Access Journals (Sweden)

    Suwana M.A.J.

    2017-08-01

    Full Text Available The purpose of this study is to examine the moderating effect of earning management on corporate governance mechanism, ownership structure, and external auditor toward corporate social responsibility disclosure. This study finds that the increase of ownership structure (foreign ownership and institutional ownership will increase corporate social responsibility disclosure. However corporate governance mechanism and external auditor is not affecting corporate social responsibility disclosure. Furthermore, this study provides additional empirical evidence for agency theory especially agency cost, that corporate governance mechanism, ownership structure, and Big Four audit firm do not have an effective role as agency cost to prevent or decrease earning management practice.

  19. Ecological mechanisms underlying soil bacterial responses to rainfall along a steep natural precipitation gradient.

    Science.gov (United States)

    Waring, Bonnie; Hawkes, Christine V

    2018-02-01

    Changes in the structure and function of soil microbial communities can drive substantial ecosystem feedbacks to altered precipitation. However, the ecological mechanisms underlying community responses to environmental change are not well understood. We used an 18-month soil reciprocal transplant experiment along a steep precipitation gradient to quantify how changes in rainfall affected bacterial community structure. We also conducted an enhanced dispersal treatment to ask whether higher immigration rates of taxa from the surrounding environment would accelerate community responses to climate change. Finally, we addressed how the composition of soil bacteria communities was related to the functional response of soil respiration to moisture in these treatments. Bacterial community structure (OTU abundance) and function (respiration rates) changed little in response to manipulation of either rainfall environment or dispersal rates. Although most bacteria were ecological generalists, a subset of specialist taxa, over 40% of which were Actinobacteria, tended to be more abundant in the rainfall environment that matched their original conditions. Bacteria community composition was an important predictor of the respiration response to moisture. Thus, the high compositional resistance of microbial communities dictated respiration responses to altered rainfall in this system.

  20. A quantitative trait locus for a primary antibody response to keyhole limpet hemocyanin on chicken chromosome 14-Confirmation and candidate gene approach

    NARCIS (Netherlands)

    Siwek, M.; Slawinska, A.; Nieuwland, M.G.B.; Witkowski, A.; Zieba, G.; Minozzi, G.; Knol, E.F.; Bednarczyk, M.

    2010-01-01

    A QTL involved in the primary antibody response toward keyhole limpet hemocyanin (KLH) was detected on chicken chromosome 14 in the experimental population, which was created by crossing commercial White Leghorn and a Polish native chicken breed (green-legged partridgelike). The current QTL location

  1. Reciprocal Interactions between Cadmium-Induced Cell Wall Responses and Oxidative Stress in Plants

    Directory of Open Access Journals (Sweden)

    Christophe Loix

    2017-10-01

    Full Text Available Cadmium (Cd pollution renders many soils across the world unsuited or unsafe for food- or feed-orientated agriculture. The main mechanism of Cd phytotoxicity is the induction of oxidative stress, amongst others through the depletion of glutathione. Oxidative stress can damage lipids, proteins, and nucleic acids, leading to growth inhibition or even cell death. The plant cell has a variety of tools to defend itself against Cd stress. First and foremost, cell walls might prevent Cd from entering and damaging the protoplast. Both the primary and secondary cell wall have an array of defensive mechanisms that can be adapted to cope with Cd. Pectin, which contains most of the negative charges within the primary cell wall, can sequester Cd very effectively. In the secondary cell wall, lignification can serve to immobilize Cd and create a tougher barrier for entry. Changes in cell wall composition are, however, dependent on nutrients and conversely might affect their uptake. Additionally, the role of ascorbate (AsA as most important apoplastic antioxidant is of considerable interest, due to the fact that oxidative stress is a major mechanism underlying Cd toxicity, and that AsA biosynthesis shares several links with cell wall construction. In this review, modifications of the plant cell wall in response to Cd exposure are discussed. Focus lies on pectin in the primary cell wall, lignification in the secondary cell wall and the importance of AsA in the apoplast. Regarding lignification, we attempt to answer the question whether increased lignification is merely a consequence of Cd toxicity, or rather an elicited defense response. We propose a model for lignification as defense response, with a central role for hydrogen peroxide as substrate and signaling molecule.

  2. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    Science.gov (United States)

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  3. Low Complexity Signed Response Based Sybil Attack Detection Mechanism in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    M. Saud Khan

    2016-01-01

    Full Text Available Security is always a major concern in wireless sensor networks (WSNs. Identity based attacks such as spoofing and sybil not only compromise the network but also slow down its performance. This paper proposes a low complexity sybil attack detection scheme, that is, based on signed response (SRES authentication mechanism developed for Global System for Mobile (GSM communications. A probabilistic model is presented which analyzes the proposed authentication mechanism for its probability of sybil attack. The paper also presents a simulation based comparative analysis of the existing sybil attack schemes with respect to the proposed scheme. It is observed that the proposed sybil detection scheme exhibits lesser computational cost and power consumption as compared to the existing schemes for the same sybil detection performance.

  4. Photooptical response of the blood plasma to the low-intensity red light

    International Nuclear Information System (INIS)

    Mints, R.I.; Skopinov, S.A.; Yakovleva, S.V.

    1990-01-01

    Photooptical response to low-intensity red light by irradiation of the whole blood as well as of its pigmentless plasma part is investigated. It is shown by the example of blood irradiation that the mechanism of action of low-intensity red light on the blood is not directly related to pigmented molecular complexes. The conclusion is made, that the effect of low-intensity red light on living organisms includes mechanism not utilizing light absorption by a specialized molecule-photoreceptor as a primary photophysical act

  5. 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).

  6. Intravenous IgA complexed with antigen reduces primary antibody response to the antigen and anaphylaxis upon antigen re-exposure by inhibiting Th1 and Th2 activation in mice.

    Science.gov (United States)

    Yamaki, Kouya; Miyatake, Kenji; Nakashima, Takayuki; Morioka, Ayumi; Yamamoto, Midori; Ishibashi, Yuki; Ito, Ayaka; Kuranishi, Ayu; Yoshino, Shin

    2014-10-01

    Serum IgG, IgE and IgM have been shown to enhance the primary antibody responses upon exposure to the soluble antigens recognized by those antibodies. However, how IgA affects these responses remains unknown. We investigated the effects of intravenously administered monoclonal IgA on the immune responses in mice. DBA/1J mice were immunized with ovalbumin in the presence or absence of anti-ovalbumin monoclonal IgA. The Th1 and Th2 immune responses to ovalbumin and the anaphylaxis induced by re-exposure to ovalbumin were measured. IgA complexed with antigen attenuated the primary antibody responses to the antigen in mice, in contrast to IgG2b and IgE. The primary antibody responses, i.e. the de novo synthesis of anti-ovalbumin IgG2a, IgG1 and IgE in the serum, and the subsequent anaphylaxis induced with re-exposure to ovalbumin were reduced by the co-injection of anti-ovalbumin monoclonal IgA at ovalbumin immunization. The Th1, Th2 and Tr1 cytokines interferon-γ, interleukin-4 and interleukin-10, respectively, released from ovalbumin-restimulated cultured splenocytes collected from allergic mice were also reduced by the treatment. The induction of interferon-γ and interleukin-4 secretion by splenocytes from ovalbumin-immunized mice stimulated in vitro with ovalbumin was also significantly reduced by the antigen complexed with anti-ovalbumin IgA. These data suggest that the direct inhibition of Th1 and Th2 activation by anti-ovalbumin monoclonal IgA participates in the inhibition of the primary antibody responses. IgA plays important immunosuppressive roles under physiological and pathological conditions and is a promising candidate drug for the treatment of immune disorders.

  7. Study of the Genes and Mechanism Involved in the Radioadaptive Response

    Science.gov (United States)

    Dasgupta, Pushan R.

    2009-01-01

    The radioadaptive response is a phenomenon where exposure to a prior low dose of radiation reduces the level of damage induced by a subsequent high radiation dose. The molecular mechanism behind this is still not well understood. Learning more about the radioadaptive response is critical for long duration spaceflight since astronauts are exposed to low levels of cosmic radiation. The micronucleus assay was used to measure the level of damage caused by radiation. Although cells which were not washed with phosphate buffered saline (PBS) after a low priming dose of 5cGy did not show adaptation to the challenge dose, washing the cells with PBS and giving the cells fresh media after the low dose did allow radioadaptation to occur. This is consistent with the results of a previous publication by another research group. In the present study, genes involved in DNA damage signaling and the oxidative stress response were studied using RT PCR techniques in order to look at changes in expression level after the low dose with or without washing. Our preliminary results indicate that upregulation of oxidative stress response genes ANGPTL7, NCF2, TTN, and SRXN1 may be involved in the radioadaptive response. The low dose of radiation alone was found to activate the oxidative stress response genes GPR156 and MTL5, whereas, washing the cells alone caused relatively robust upregulation of the oxidative stress response genes DUSP1 and PTGS2. Washing after the priming dose showed some changes in the expression level of several DNA damage signaling genes. In addition, we studied whether washing the cells after the priming dose has an effect on the level of nitric oxide in both the media and cells, since nitric oxide levels are known to increase in the media of the cells after a high dose of radiation only if the cells were already exposed to a low priming dose. Based on this preliminary study, we propose that washing the cells after priming exposure actually eliminates some factor

  8. Net primary productivity and its partitioning in response to precipitation gradient in an alpine meadow.

    Science.gov (United States)

    Zhang, Fangyue; Quan, Quan; Song, Bing; Sun, Jian; Chen, Youjun; Zhou, Qingping; Niu, Shuli

    2017-11-09

    The dynamics of net primary productivity (NPP) and its partitioning to the aboveground versus belowground are of fundamental importance to understand carbon cycling and its feedback to climate change. However, the responses of NPP and its partitioning to precipitation gradient are poorly understood. We conducted a manipulative field experiment with six precipitation treatments (1/12 P, 1/4 P, 1/2 P, 3/4 P, P, and 5/4 P, P is annual precipitation) in an alpine meadow to examine aboveground and belowground NPP (ANPP and BNPP) in response to precipitation gradient in 2015 and 2016. We found that changes in precipitation had no significant impact on ANPP or belowground biomass in 2015. Compared with control, only the extremely drought treatment (1/12 P) significantly reduced ANPP by 37.68% and increased BNPP at the depth of 20-40 cm by 80.59% in 2016. Across the gradient, ANPP showed a nonlinear response to precipitation amount in 2016. Neither BNPP nor NPP had significant relationship with precipitation changes. The variance in ANPP were mostly due to forbs production, which was ultimately caused by altering soil water content and soil inorganic nitrogen concentration. The nonlinear precipitation-ANPP relationship indicates that future precipitation changes especially extreme drought will dramatically decrease ANPP and push this ecosystem beyond threshold.

  9. Features of formation of the mechanism of introduction of the corporate social responsibility in activity the domestic industrial enterprises

    OpenAIRE

    Antoshko, T.

    2011-01-01

    Article opens essence of the corporate social responsibility (CSR), its components and principles CSR. The developed process model of formation of the mechanism of introduction CSR on the basis of disclosing principles of directions CSR. The mechanism of introduction CSR at the enterprise is developed. As criterion of an assessment of the mechanism of introduction CSR it has been suggested factor of activity of use of components of the mechanism of introduction CSR.

  10. Neural mechanisms of mismatch negativity dysfunction in schizophrenia.

    Science.gov (United States)

    Lee, M; Sehatpour, P; Hoptman, M J; Lakatos, P; Dias, E C; Kantrowitz, J T; Martinez, A M; Javitt, D C

    2017-11-01

    Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls. rsfcMRI was obtained from a subsample of 38 patients and 23 controls. As expected, schizophrenia patients showed highly significant, large effect size (P=0.0004, d=1.0) deficits in MMN generation across deviant types. In ERSP analyses, responses to deviants occurred primarily the theta (4-7 Hz) frequency range consistent with distributed corticocortical processing, whereas responses to standards occurred primarily in alpha (8-12 Hz) range consistent with known frequencies of thalamocortical activation. Independent deficits in schizophrenia were observed in both the theta response to deviants (P=0.021) and the alpha-response to standards (P=0.003). At the single-trial level, differential patterns of response were observed for frequency vs duration/intensity deviants, along with At the network level, MMN deficits engaged canonical somatomotor, ventral attention and default networks, with a differential pattern of engagement across deviant types (Pschizophrenia. In addition, differences in ERSP and rsfcMRI profiles across deviant types suggest potential differential engagement of underlying generator mechanisms.

  11. 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....

  12. Prediction of Unmet Primary Care Needs for the Medically Vulnerable Post-Disaster: An Interrupted Time-Series Analysis of Health System Responses

    Directory of Open Access Journals (Sweden)

    Amy B. Martin

    2012-09-01

    Full Text Available Disasters serve as shocks and precipitate unanticipated disturbances to the health care system. Public health surveillance is generally focused on monitoring latent health and environmental exposure effects, rather than health system performance in response to these local shocks. The following intervention study sought to determine the long-term effects of the 2005 chlorine spill in Graniteville, South Carolina on primary care access for vulnerable populations. We used an interrupted time-series approach to model monthly visits for Ambulatory Care Sensitive Conditions, an indicator of unmet primary care need, to quantify the impact of the disaster on unmet primary care need in Medicaid beneficiaries. The results showed Medicaid beneficiaries in the directly impacted service area experienced improved access to primary care in the 24 months post-disaster. We provide evidence that a health system serving the medically underserved can prove resilient and display improved adaptive capacity under adverse circumstances (i.e., technological disasters to ensure access to primary care for vulnerable sub-groups. The results suggests a new application for ambulatory care sensitive conditions as a population-based metric to advance anecdotal evidence of secondary surge and evaluate pre- and post-health system surge capacity following a disaster.

  13. The body’s immune response in the induction and progression of cancer of the cervix uteri: possible mechanisms

    Directory of Open Access Journals (Sweden)

    O. V. Kurmyshkina

    2011-01-01

    Full Text Available Human papillomavirus (HPV that is a main cause of cancer of the cervix uteri (CCU has immunogenic properties, i.e. an abilityto activate antiviral immunity responses as adaptive HPV-specific and innate ones. For this reason, despite multiple mechanisms generated by HPV to avoid immunity responses, the human body can eliminate the infection in most cases. At the same time, CCU results from the combined influence of many factors of different nature, among which the factors that impair the normal course of an immune response are of vital importance.This review describes the major factors and mechanisms, which promote the establishment of persistent HPV infection and the progression of dysplasia to cancer, on the one hand, and allow the tumor cells in CCU to restrict the body’s immune reactions, on the other Immune disorders induced by the virus and/or tumor cells are considered at both local and systemic levels. Particular emphasis is placed on the molecular mechanisms that can change the population composition and functional activity of leukocytes and the cytokine profile of cells and can form the tumor suppressor microenvironment.

  14. Response of the primary tumor in symptomatic and asymptomatic stage IV colorectal cancer to combined interventional endoscopy and palliative chemotherapy

    International Nuclear Information System (INIS)

    Cameron, Silke; Hünerbein, Diana; Mansuroglu, Tümen; Armbrust, Thomas; Scharf, Jens-Gerd; Schwörer, Harald; Füzesi, László; Ramadori, Giuliano

    2009-01-01

    The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease. 20 patients [14 men, 6 women, median age 67 (39–82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy. Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3–71) months. No complications due to the primary were observed. This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC

  15. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    International Nuclear Information System (INIS)

    Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.; Issitt, Theo; Ulyatt, Clare; Walker, John H.; Homer-Vanniasinkam, Shervanthi; Ponnambalam, Sreenivasan

    2012-01-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

  16. Modelling and simulating the forming of new dry automated lay-up reinforcements for primary structures

    Science.gov (United States)

    Bouquerel, Laure; Moulin, Nicolas; Drapier, Sylvain; Boisse, Philippe; Beraud, Jean-Marc

    2017-10-01

    While weight has been so far the main driver for the development of prepreg based-composites solutions for aeronautics, a new weight-cost trade-off tends to drive choices for next-generation aircrafts. As a response, Hexcel has designed a new dry reinforcement type for aircraft primary structures, which combines the benefits of automation, out-of-autoclave process cost-effectiveness, and mechanical performances competitive to prepreg solutions: HiTape® is a unidirectional (UD) dry carbon reinforcement with thermoplastic veil on each side designed for aircraft primary structures [1-3]. One privileged process route for HiTape® in high volume automated processes consists in forming initially flat dry reinforcement stacks, before resin infusion [4] or injection. Simulation of the forming step aims at predicting the geometry and mechanical properties of the formed stack (so-called preform) for process optimisation. Extensive work has been carried out on prepreg and dry woven fabrics forming behaviour and simulation, but the interest for dry non-woven reinforcements has emerged more recently. Some work has been achieved on non crimp fabrics but studies on the forming behaviour of UDs are seldom and deal with UD prepregs only. Tension and bending in the fibre direction, along with inter-ply friction have been identified as the main mechanisms controlling the HiTape® response during forming. Bending has been characterised using a modified Peirce's flexometer [5] and inter-ply friction study is under development. Anisotropic hyperelastic constitutive models have been selected to represent the assumed decoupled deformation mechanisms. Model parameters are then identified from associated experimental results. For forming simulation, a continuous approach at the macroscopic scale has been selected first, and simulation is carried out in the Zset framework [6] using proper shell finite elements.

  17. Influence of primary α-phase volume fraction on the mechanical properties of Ti-6Al-4V alloy at different strain rates and temperatures

    Science.gov (United States)

    Ren, Yu; Zhou, Shimeng; Luo, Wenbo; Xue, Zhiyong; Zhang, Yajing

    2018-03-01

    Bimodal microstructures with primary α-phase volume fractions ranging from 14.3% to 57.1% were gained in Ti-6Al-4V (Ti-64) alloy through annealed in two-phase region at various temperatures below the β-transus point. Then the influence of the primary α-phase volume fraction on the mechanical properties of Ti-64 were studied. The results show that, at room temperature and a strain rate of 10‑3 s‑1, the yield stress decreases but the fracture strain augments with added primary α-phase volume fraction. The equiaxed primary α-phase possesses stronger ability to coordinate plastic deformation, leading to the improvement of the ductile as well as degradation of the strength of Ti-64 with higher primary α-phase volume fraction. As the temperature goes up to 473 K, the quasi-static yield stress and ultimate strength decrease first and then increase with the incremental primary α-phase volume fraction, due to the interaction between the work hardening and the softening caused by the DRX and the growth of the primary α-phase. At room temperature and a strain rate of 3×103 s‑1, the varying pattern of strength with the primary α-phase volume fraction resembles that at a quasi-static strain rate. However, the flow stress significantly increases but the strain-hardening rate decreases compared to those at quasi-static strain rate due to the competition between the strain rate hardening and the thermal softening during dynamic compression process.

  18. Artifact correction and source analysis of early electroencephalographic responses evoked by transcranial magnetic stimulation over primary motor cortex.

    Science.gov (United States)

    Litvak, Vladimir; Komssi, Soile; Scherg, Michael; Hoechstetter, Karsten; Classen, Joseph; Zaaroor, Menashe; Pratt, Hillel; Kahkonen, Seppo

    2007-08-01

    Analyzing the brain responses to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) is a promising method for the assessment of functional cortical connectivity and excitability of areas accessible to this stimulation. However, until now it has been difficult to analyze the EEG responses during the several tens of milliseconds immediately following the stimulus due to TMS-induced artifacts. In the present study we show that by combining a specially adapted recording system with software artifact correction it is possible to remove a major part of the artifact and analyze the cortical responses as early as 10 ms after TMS. We used this methodology to examine responses of left and right primary motor cortex (M1) to TMS at different intensities. Based on the artifact-corrected data we propose a model for the cortical activation following M1 stimulation. The model revealed the same basic response sequence for both hemispheres. A large part of the response could be accounted for by two sources: a source close to the stimulation site (peaking approximately 15 ms after the stimulus) and a midline frontal source ipsilateral to the stimulus (peaking approximately 25 ms). In addition the model suggests responses in ipsilateral temporo-parietal junction areas (approximately 35 ms) and ipsilateral (approximately 30 ms) and middle (approximately 50 ms) cerebellum. Statistical analysis revealed significant dependence on stimulation intensity for the ipsilateral midline frontal source. The methodology developed in the present study paves the way for the detailed study of early responses to TMS in a wide variety of brain areas.

  19. Jatropha curcasand Ricinus communisdisplay contrasting photosynthetic mechanisms in response to environmental conditions

    Directory of Open Access Journals (Sweden)

    Milton Costa Lima Neto

    2015-06-01

    Full Text Available Higher plants display different adaptive strategies in photosynthesis to cope with abiotic stress. In this study, photosynthetic mechanisms and water relationships displayed byJatropha curcasL. (physic nuts andRicinus communisL. (castor bean, in response to variations in environmental conditions, were assessed.R. communis showed higher CO2 assimilation, stomatal and mesophyll conductance thanJ. curcas as light intensity and intercellular CO2 pressure increased. On the other hand,R. communis was less effective in stomatal control in response to adverse environmental factors such as high temperature, water deficit and vapor pressure deficit, indicating lower water use efficiency. Conversely,J. curcas exhibited higher photosynthetic efficiency (gas exchange and photochemistry and water use efficiency under these adverse environmental conditions.R. communisdisplayed higher potential photosynthesis, but exhibited a lowerin vivo Rubisco carboxylation rate (Vcmax and maximum electron transport rate (Jmax. During the course of a typical day, in a semiarid environment, with high irradiation, high temperature and high vapor pressure deficit, but exposed to well-watered conditions, the two studied species presented similar photosynthesis. Losing potential photosynthesis, but maintaining favorable water status and increasing non-photochemical quenching to avoid photoinhibition, are important acclimation mechanisms developed byJ. curcas to cope with dry and hot conditions. We suggest thatJ. curcas is more tolerant to hot and dry environments thanR. communis but the latter species displays higher photosynthetic efficiency under well-watered and non-stressful conditions.

  20. Manifestation of Particle Morphology on the Mechanical Response of a Granular Ensemble

    Science.gov (United States)

    Murthy, Tejas; Kandasami, Ramesh

    We present the effect of particle morphology (grain shape) on the mechanical response of granular materials at an ensemble level. We chose two model systems with extreme differences in morphology, i.e. spherical glass ballotini and angular sand in our experimental programme. We conducted a series of continuum elemental tests under these model materials reconstituted to the same packing. We arrive at the failure locus on the octahedral plane experimentally for these two systems. The ballotini shows increased dilation at the outset of the test, however, at large strains, the particle rearrangement in the angular sand and the increased interlocking leads to higher strength. The effect of individual particle morphology is manifested in both the increased friction angle and a larger sized failure locus in stress space with increase in angularity. The stresses developed in these two model materials are also accompanied by intriguing volume change behaviour. The glass ballotini despite a lower strength presents a predominantly dilative response while the angular sand shows showing a contractive response. Such an ensemble manifestation of individual particle morphology is useful in interpreting the extensive DEM simulations that are available in literature.

  1. Total elbow arthroplasty for primary osteoarthritis.

    Science.gov (United States)

    Schoch, Bradley S; Werthel, Jean-David; Sánchez-Sotelo, Joaquín; Morrey, Bernard F; Morrey, Mark

    2017-08-01

    Primary osteoarthritis of the elbow is a less common indication for total elbow arthroplasty (TEA). Higher complication rates in younger, active patients may offset short-term improvements in pain and function. The purpose of this study was to determine pain relief, functional outcomes, complications, and survival of TEA in this population. Between 1984 and 2011, 20 consecutive TEAs were performed for primary elbow osteoarthritis. Two patients died before the 2-year follow-up. Mean age at surgery was 68 years (range, 51-85 years). Outcome measures included pain, motion, Mayo Elbow Performance Score, satisfaction, complications, and reoperations. Mean follow-up was 8.9 years (range, 2-20 years). Three elbows sustained mechanical failures. Complications included intraoperative fracture (n = 2), wound irrigation and débridement (n = 1), bony ankylosis (n = 1), humeral loosening (n = 1), humeral component fracture (n = 1), and mechanical failure of a radial head component (n = 1). Fifteen elbows without mechanical failure were examined clinically. Pain improved from 3.6 to 1.5 (P  .05), with preoperative flexion contractures not improving. Mayo Elbow Performance Scores were available for 13 elbows without mechanical failure, averaging 81.5 points (range, 60-100 points); these were graded as excellent (n = 5), good (n = 2), and fair (n = 6). Subjectively, all patients without mechanical failure were satisfied. TEA represents a reliable surgical option for pain relief in patients with primary osteoarthritis. However, restoration of extension is not always obtained, indicating that more aggressive soft tissue releases or bony resection should be considered. Complications occurred in a large number of elbows, but mechanical failure was low considering the nature of this population and the length of follow-up. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  2. Theory of the mechanical response of focal adhesions to shear flow

    International Nuclear Information System (INIS)

    Biton, Y Y; Safran, S A

    2010-01-01

    The response of cells to shear flow is primarily determined by the asymmetry of the external forces and moments that are sensed by each member of a focal adhesion pair connected by a contractile stress fiber. In the theory presented here, we suggest a physical model in which each member of such a pair of focal adhesions is treated as an elastic body subject to both a myosin-activated contractile force and the shear stress induced by the external flow. The elastic response of a focal adhesion complex is much faster than the active cellular processes that determine the size of the associated focal adhesions and the direction of the complex relative to the imposed flow. Therefore, the complex attains its mechanical equilibrium configuration which may change because of the cellular activity. Our theory is based on the experimental observation that focal adhesions modulate their cross-sectional area in order to attain an optimal shear. Using this assumption, our elastic model shows that such a complex can passively change its orientation to align parallel to the direction of the flow.

  3. Beryllium-specific immune response in primary cells from healthy individuals

    International Nuclear Information System (INIS)

    Chaudhary, Anu; Sauer, Nancy N.; Gupta, Goutam

    2004-01-01

    The effect of beryllium (Be) exposure has been extensively studied in patients with chronic beryllium disease (CBD). CBD patients carry mutated MHC class II alleles and show a hyperproliferation of T cells upon Be exposure. The exact mechanism of Be-induced T-cell proliferation in these patients is not clearly understood. It is also not known how the inflammatory and suppressive cytokines maintain a balance in healthy individuals and how this balance is lost in CBD patients. To address these issues, we have initiated cellular and biochemical studies to identify Be-responsive cytokines and other cellular markers that help maintain a balance in healthy individuals. We have established an immune cell model derived from a mixture of peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs). In this article, we demonstrate that pro-inflammatory cytokine IL6 shows decreased release whereas suppressive cytokine IL10 shows enhanced release after 5-10 h of Be treatment. Furthermore, the Be-specific pattern of IL6 and IL10 release is dependent upon induction of threonine phosphorylation of a 45 kDa cytosolic protein (p45), as early as 90 min after Be treatment. Pharmacological inhibition of phosphatidylinositol 3' kinase (PI3'K) by wortmannin and p38 mitogen-activated protein kinase (MAPK) by SB203580 reveal that PI3'K mediates Be-specific p45 phosphorylation and IL6 release, whereas p38 MAPK regulates the release of IL6 and IL10 and the phosphorylation of p45 independent of metal-salt treatment. While the IL10 and IL6 release pathways are uncoupled in these cells, they are linked to phosphorylation of p45. These findings suggest that the balance between IL10 and IL6 release and the correlated p45 phosphorylation are important components of the Be-mediated immune response in healthy individuals

  4. Factorial Study of Compressive Mechanical Properties and Primary In Vitro Osteoblast Response of PHBV/PLLA Scaffolds

    Directory of Open Access Journals (Sweden)

    Naznin Sultana

    2012-01-01

    Full Text Available For bone tissue regeneration, composite scaffolds containing biodegradable polymers and nanosized osteoconductive bioceramics have been regarded as promising biomimetic systems. Polymer blends of poly(hydroxybutyrate-co-hydroxyvalerate (PHBV and poly(L-lactic acid (PLLA can be used as the polymer matrix to control the degradation rate. In order to render the scaffolds osteoconductive, nano-sized hydroxyapatite (nHA particles can be incorporated into the polymer matrix. In the first part of this study, a factorial design approach to investigate the influence of materials on the initial compressive mechanical properties of the scaffolds was studied. In the second part, the protein adsorption behavior and the attachment and morphology of osteoblast-like cells (Saos-2 of the scaffolds in vitro were also studied. It was observed that nHA incorporated PHBV/PLLA composite scaffolds adsorbed more bovine serum albumin (BSA protein than PHBV or PHBV/PLLA scaffolds. In vitro studies also revealed that the attachment of human osteoblastic cells (SaOS-2 was significantly higher in nHA incorporated PHBV/PLLA composite scaffolds. From the SEM micrographs of nHA incorporated PHBV/PLLA composite scaffolds seeded with SaOS-2 cells after a 7-day cell culture period, it was observed that the cells were well expanded and spread in all directions on the scaffolds.

  5. 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

  6. Clinical Outcome and Predictive Factors in the Response to Splenectomy in Elderly Patients with Primary Immune Thrombocytopenia: A Multicenter Retrospective Study.

    Science.gov (United States)

    Park, Young Hoon; Yi, Hyeon Gyu; Kim, Chul Soo; Hong, Junshik; Park, Jinny; Lee, Jae Hoon; Kim, Ho Young; Kim, Hyo Jung; Zang, Dae Young; Kim, Se Hyung; Park, Seong Kyu; Hong, Dae Sik; Lee, Guk Jin; Jin, Jong-Youl

    2016-01-01

    Because many physicians seem reluctant to recommend splenectomy for elderly patients with immune thrombocytopenia (ITP), we investigated the safety and efficacy of splenectomy and the predictive factors for response in these patients. 184 patients with primary ITP were retrospectively analyzed based on age at splenectomy: an elderly group (≥60 years, n = 52) and a younger group (splenectomy (HR 2.9, 95% CI: 1.24-6.80, p = 0.014) and platelet count on postoperative day 14 ≥200 × 109/l (HR 31.43, 95% CI: 4.15-238.28, p = 0.001) were independent factors for a favorable response. Age ≥60 years did not influence the response to splenectomy but was associated with increased relapse and postoperative complications. Splenectomy could provide a durable long-term response for elderly ITP patients. © 2016 S. Karger AG, Basel.

  7. Plants know where it hurts: root and shoot jasmonic acid induction elicit differential responses in Brassica oleracea.

    Directory of Open Access Journals (Sweden)

    Tom O G Tytgat

    Full Text Available Plants respond to herbivore attack by rapidly inducing defenses that are mainly regulated by jasmonic acid (JA. Due to the systemic nature of induced defenses, attack by root herbivores can also result in a shoot response and vice versa, causing interactions between above- and belowground herbivores. However, little is known about the molecular mechanisms underlying these interactions. We investigated whether plants respond differently when roots or shoots are induced. We mimicked herbivore attack by applying JA to the roots or shoots of Brassica oleracea and analyzed molecular and chemical responses in both organs. In shoots, an immediate and massive change in primary and secondary metabolism was observed. In roots, the JA-induced response was less extensive and qualitatively different from that in the shoots. Strikingly, in both roots and shoots we also observed differential responses in primary metabolism, development as well as defense specific traits depending on whether the JA induction had been below- or aboveground. We conclude that the JA response is not only tissue-specific but also dependent on the organ that was induced. Already very early in the JA signaling pathway the differential response was observed. This indicates that both organs have a different JA signaling cascade, and that the signal eliciting systemic responses contains information about the site of induction, thus providing plants with a mechanism to tailor their responses specifically to the organ that is damaged.

  8. Exposing primary rat retina cell cultures to γ-rays: An in vitro model for evaluating radiation responses.

    Science.gov (United States)

    Gaddini, Lucia; Balduzzi, Maria; Campa, Alessandro; Esposito, Giuseppe; Malchiodi-Albedi, Fiorella; Patrono, Clarice; Matteucci, Andrea

    2018-01-01

    Retinal tissue can receive incidental γ-rays exposure during radiotherapy either of tumors of the eye and optic nerve or of head-and-neck tumors, and during medical diagnostic procedures. Healthy retina is therefore at risk of suffering radiation-related side effects and the knowledge of pathophysiological response of retinal cells to ionizing radiations could be useful to design possible strategies of prevention and management of radiotoxicity. In this study, we have exploited an in vitro model (primary rat retinal cell culture) to study an array of biological effects induced on retinal neurons by γ-rays. Most of the different cell types present in retinal tissue - either of the neuronal or glial lineages - are preserved in primary rat retinal cultures. Similar to the retina in situ, neuronal cells undergo in vitro a maturational development shown by the formation of polarized neuritic trees and operating synapses. Since 2 Gy is the incidental dose received by the healthy retina per fraction when the standard treatment is delivered to the brain, retina cell cultures have been exposed to 1 or 2 Gy of γ-rays at different level of neuronal differentiation in vitro: days in vitro (DIV)2 or DIV8. At DIV9, retinal cultures were analyzed in terms of viability, apoptosis and characterized by immunocytochemistry to identify alterations in neuronal differentiation. After irradiation at DIV2, MTT assay revealed an evident loss of cell viability and βIII-tubulin immunostaining highlighted a marked neuritic damage, indicating that survived neurons showed an impaired differentiation. Differentiated cultures (DIV8) appeared to be more resistant with respect to undifferentiated, DIV2 cultures, both in terms of cell viability and differentiation. Apoptosis evaluated with TUNEL assay showed that irradiation at both DIV2 and DIV8 induced a significant increase in the apoptotic rate. To further investigate the effects of γ-rays on retinal neurons, we evaluated the

  9. Thermal-mechanical-hydrological-chemical responses in the single heater test at the ESF

    International Nuclear Information System (INIS)

    Lin, W.; Blair, S.; Buettner, M

    1997-01-01

    The Single Heater Test (SHT) is conducted in the Exploratory Studies Facility (ESF) to study the thermal-mechanical responses of the rock mass. A set of boreholes were drilled in the test region for conducting a scoping test of the coupled thermal-mechanical- hydrological-chemical (TMHC) processes. The holes for the TMHC tests include electrical resistivity tomography (ERT), neutron logging/temperature, hydrological, and optical multiple point borehole extensometers. A 4-kW heater was installed in the heater hole, and was energized on August 26, 1996. Some observed movements of the water around the heater are associated with a possible dry-out region near the heater. The water that has been moved is more dilute than the in situ ground water, except for the concentration of Ca. This indicates that fractures are the major water pathways, and the displaced water may have reached an equilibrium with carbonate minerals on the fracture surfaces. No mechanical-hydrological coupling has been observed. The tests are on-going, and more data will be collected and analyzed

  10. Benthic reef primary production in response to large amplitude internal waves at the Similan Islands (Andaman Sea, Thailand)

    KAUST Repository

    Jantzen, Carin

    2013-11-29

    Coral reefs are facing rapidly changing environments, but implications for reef ecosystem functioning and important services, such as productivity, are difficult to predict. Comparative investigations on coral reefs that are naturally exposed to differing environmental settings can provide essential information in this context. One prevalent phenomenon regularly introducing alterations in water chemistry into coral reefs are internal waves. This study therefore investigates the effect of large amplitude internal waves (LAIW) on primary productivity in coral reefs at the Similan Islands (Andaman Sea, Thailand). The LAIW-exposed west sides of the islands are subjected to sudden drops in water temperature accompanied by enhanced inorganic nutrient concentrations compared to the sheltered east. At the central island, Ko Miang, east and west reefs are only few hundred meters apart, but feature pronounced differences. On the west lower live coral cover (-38%) coincides with higher turf algae cover (+64%) and growth (+54%) compared to the east side. Turf algae and the reef sand-associated microphytobenthos displayed similar chlorophyll a contents on both island sides, but under LAIW exposure, turf algae exhibited higher net photosynthesis (+23%), whereas the microphytobenthos displayed reduced net and gross photosynthesis (-19% and -26%, respectively) accompanied by lower respiration (-42%). In contrast, the predominant coral Porites lutea showed higher chlorophyll a tissues contents (+42%) on the LAIW-exposed west in response to lower light availability and higher inorganic nutrient concentrations, but net photosynthesis was comparable for both sides. Turf algae were the major primary producers on the west side, whereas microphytobenthos dominated on the east. The overall primary production rate (comprising all main benthic primary producers) was similar on both island sides, which indicates high primary production variability under different environmental conditions.

  11. Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy

    Directory of Open Access Journals (Sweden)

    Lucy C. Fox

    2018-06-01

    Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p.L265P mutation. Ibrutinib therapy was subsequently commenced, resulting in complete resolution of the skin disease. Despite an ongoing skin response, the patient developed progressive nodal disease at two months. Genomic analysis of the cutaneous tumor sample at baseline was compared to that of the inguinal lymph node upon progression, and revealed the acquisition of multiple genomic changes. These included several aberrations expected to bypass BTK inhibition, including two CARD11-activating mutations, and a deleterious mutation in the nuclear factor kappa B (NF-κB negative regulator, NFKBIE. In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus, representing a third plausible mechanism contributing to ibrutinib resistance. Several copy-number changes occurred in both samples, including an amplification of 18q, which encodes the anti-apoptotic protein BCL2. We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance.

  12. Cancer Survivorship Care Plan Utilization and Impact on Clinical Decision-Making at Point-of-Care Visits with Primary Care: Results from an Engineering, Primary Care, and Oncology Collaborative for Survivorship Health.

    Science.gov (United States)

    Donohue, SarahMaria; Haine, James E; Li, Zhanhai; Feldstein, David A; Micek, Mark; Trowbridge, Elizabeth R; Kamnetz, Sandra A; Sosman, James M; Wilke, Lee G; Sesto, Mary E; Tevaarwerk, Amye J

    2017-11-02

    Every cancer survivor and his/her primary care provider should receive an individualized survivorship care plan (SCP) following curative treatment. Little is known regarding point-of-care utilization at primary care visits. We assessed SCP utilization in the clinical context of primary care visits. Primary care physicians and advanced practice providers (APPs) who had seen survivors following provision of an SCP were identified. Eligible primary care physicians and APPs were sent an online survey, evaluating SCP utilization and influence on decision-making at the point-of-care, accompanied by copies of the survivor's SCP and the clinic note. Eighty-eight primary care physicians and APPs were surveyed November 2016, with 40 (45%) responding. Most respondents (60%) reported discussing cancer or related issues during the visit. Information needed included treatment (66%) and follow-up visits, and the cancer team was responsible for (58%) vs primary care (58%). Respondents acquired this information by asking the patient (79%), checking oncology notes (75%), the SCP (17%), or online resources (8%). Barriers to SCP use included being unaware of the SCP (73%), difficulty locating it (30%), and finding needed information faster via another mechanism (15%). Despite largely not using the SCP for the visit (90%), most respondents (61%) believed one would be quite or very helpful for future visits. Most primary care visits included discussion of cancer or cancer-related issues. SCPs may provide the information necessary to deliver optimal survivor care but efforts are needed to reduce barriers and design SCPs for primary care use.

  13. PRIMARY PALLIATIVE CARE? - Treating terminally ill cancer patients in the primary care sector

    DEFF Research Database (Denmark)

    Neergaard, Mette Asbjørn; Jensen, Anders Bonde; Olesen, Frede

    BACKGROUND. Palliative care for cancer patients is an important part of a GP's work. Although every GP is frequently involved in care for terminally ill cancer patients, only little is known about how these palliative efforts are perceived by the patients and their families, a knowledge...... that is vital to further improve palliative care in the primary sector.AIM. The aim of the study was to analyse the quality of palliative home care with focus on the GP's role based on evaluations by relatives of recently deceased cancer patients and professionals from both the primary and secondary health care...... approach.RESULTS. The analyses revealed several key areas, e.g.: 1) How to take, give and maintain professional responsibility for palliative home care. 2) A need for transparent communication both among primary care professionals and among professionals across the primary/secondary interface. 3...

  14. Neurophysiological mechanisms underlying sex- and maturation-related variation in pheromone responses in honey bees (Apis mellifera).

    Science.gov (United States)

    Villar, Gabriel; Baker, Thomas C; Patch, Harland M; Grozinger, Christina M

    2015-07-01

    In the honey bee (Apis mellifera), social organization is primarily mediated by pheromones. Queen-produced 9-oxo-2-decenoic acid (9-ODA) functions as both a social and sex pheromone, eliciting attraction in both female workers and male drones, but also affecting other critical aspects of worker physiology and behavior. These effects are also maturation related, as younger workers and sexually mature drones are most receptive to 9-ODA. While changes in the peripheral nervous system drive sex-related differences in sensitivity to 9-ODA, the mechanisms driving maturation-related shifts in receptivity to 9-ODA remain unknown. Here, we investigate the hypothesis that changes at the peripheral nervous system may be mediating plastic responses to 9-ODA by characterizing expression levels of AmOR11 (the olfactory receptor tuned to 9-ODA) and electrophysiological responses to 9-ODA. We find that receptor expression correlates significantly with behavioral receptivity to 9-ODA, with nurses and sexually mature drones exhibiting higher levels of expression than foragers and immature drones, respectively. Electrophysiological responses to 9-ODA were not found to correlate with behavioral receptivity or receptor expression, however. Thus, while receptor expression at the periphery exhibits a level of plasticity that correlates with behavior, the mechanisms driving maturation-dependent responsiveness to 9-ODA appear to function primarily in the central nervous system.

  15. 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

  16. The effect of grain size on the mechanical response of a metastable austenitic stainless steel

    Directory of Open Access Journals (Sweden)

    Sinclair C.W.

    2013-11-01

    Full Text Available The combination of high environmental resistance and excellent strength, elongation and energy absorption make austenitic stainless steels potentially attractive for transportation applications. In the case of metastable grades that undergo a strain induced martensitic transformation it is possible to significantly change the mechanical properties simply by changing the austenite grain size. Predicting such behaviour using physically based models is, however, extremely challenging. Here, some recent work on the coupling between grain size and mechanical response will be presented for a metastable AISI 301 LN stainless steel. Successes and continuing challenges will be highlighted.

  17. Investigation of the energy transport mechanism in the TCA tokamak by studying the plasma dynamical response

    International Nuclear Information System (INIS)

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

    1989-01-01

    The energy transport mechanisms that govern the electron temperature behaviour of a tokamak remain very badly understood and up to now no proper model has been proposed that can explain experimental observations such as profile consistency or the influence of the density profile. One approach to this problem, extensively used on TCA, is to study the dynamical response of the plasma due to externally imposed modifications of parameters which have an influence on the plasma energy content. The temporal evolution of the electron temperature will closely depend on the type and the characteristics of the implied mechanisms. Thus a detailed measurement of the dynamical response would reveal experimentally the dominant properties that would have to be taken into account in the elaboration of a model of the transport processes. Most of the results presented here were obtained by analysing the electron temperature response inferred from soft X-ray emissivity during modification of the plasma density due to either gas puffing, laser impurity ablation or alfven wave heating on TCA (a = 0.18 m, R = 0.61 m, B Φ = 1.52 T). 4 refs., 3 figs

  18. Fatigue response of a PZT multilayer actuator under high-field electric cycling with mechanical preload

    Science.gov (United States)

    Wang, Hong; Wereszczak, Andrew A.; Lin, Hua-Tay

    2009-01-01

    An electric fatigue test system was developed for evaluating the reliability of piezoelectric actuators with a mechanical loading capability. Fatigue responses of a lead zirconate titanate (PZT) multilayer actuator with a platethrough electrode configuration were studied under an electric field (1.7 times that of the coercive field of PZT material) and a concurrent mechanical preload (30.0 MPa). A total of 109 cycles was carried out. Variations in charge density and mechanical strain under the high electric field and constant mechanical loads were observed during the fatigue test. The dc and the first harmonic (at 10 Hz) dielectric and piezoelectric coefficients were subsequently characterized using fast Fourier transformation. Both the dielectric and the piezoelectric coefficients exhibited a monotonic decrease prior to 2.86×108 cycles under certain preloading conditions, and then fluctuated. Both the dielectric loss tangent and the piezoelectric loss tangent also fluctuated after a decrease. The results are interpreted and discussed with respect to domain wall activities, microdefects, and other anomalies.

  19. Mechanical stress induces neuroendocrine and immune responses of sea cucumber ( Apostichopus japonicus)

    Science.gov (United States)

    Tan, Jie; Li, Fenghui; Sun, Huiling; Gao, Fei; Yan, Jingping; Gai, Chunlei; Chen, Aihua; Wang, Qingyin

    2015-04-01

    Grading procedure in routine sea cucumber hatchery production is thought to affect juvenile sea cucumber immunological response. The present study investigated the impact of a 3-min mechanical perturbation mimicking the grading procedure on neuroendocrine and immune parameters of the sea cucumber Apostichopus japonicus. During the application of stress, concentrations of noradrenaline and dopamine in coelomic fluid increased significantly, indicating that the mechanical perturbation resulted in a transient state of stress in sea cucumbers. Coelomocytes concentration in coelomic fluid increased transiently after the beginning of stressing, and reached the maximum in 1 h. Whereas, coelomocytes phagocytosis at 3 min, superoxide anion production from 3 min to 0.5 h, acid phosphatase activity at 0.5 h, and phenoloxidase activity from 3 min to 0.5 h were all significantly down-regulated. All of the immune parameters recovered to baseline levels after the experiment was conducted for 8 h, and an immunostimulation occurred after the stress considering the phagocytosis and acid phosphatase activity. The results suggested that, as in other marine invertebrates, neuroendocrine/immune connections exist in sea cucumber A. japonicus. Mechanical stress can elicit a profound influence on sea cucumber neuroendocrine system. Neuroendocrine messengers act in turn to modulate the immunity functions. Therefore, these effects should be considered for developing better husbandry procedures.

  20. Team-based primary care: The medical assistant perspective.

    Science.gov (United States)

    Sheridan, Bethany; Chien, Alyna T; Peters, Antoinette S; Rosenthal, Meredith B; Brooks, Joanna Veazey; Singer, Sara J

    Team-based care has the potential to improve primary care quality and efficiency. In this model, medical assistants (MAs) take a more central role in patient care and population health management. MAs' traditionally low status may give them a unique view on changing organizational dynamics and teamwork. However, little empirical work exists on how team-based organizational designs affect the experiences of low-status health care workers like MAs. The aim of this study was to describe how team-based primary care affects the experiences of MAs. A secondary aim was to explore variation in these experiences. In late 2014, the authors interviewed 30 MAs from nine primary care practices transitioning to team-based care. Interviews addressed job responsibilities, teamwork, implementation, job satisfaction, and learning. Data were analyzed using a thematic networks approach. Interviews also included closed-ended questions about workload and job satisfaction. Most MAs reported both a higher workload (73%) and a greater job satisfaction (86%) under team-based primary care. Interview data surfaced four mechanisms for these results, which suggested more fulfilling work and greater respect for the MA role: (a) relationships with colleagues, (b) involvement with patients, (c) sense of control, and (d) sense of efficacy. Facilitators and barriers to these positive changes also emerged. Team-based care can provide low-status health care workers with more fulfilling work and strengthen relationships across status lines. The extent of this positive impact may depend on supporting factors at the organization, team, and individual worker levels. To maximize the benefits of team-based care, primary care leaders should recognize the larger role that MAs play under this model and support them as increasingly valuable team members. Contingent on organizational conditions, practices may find MAs who are willing to manage the increased workload that often accompanies team-based care.

  1. Prediction of transient mechanical response of type 316 stainless steel cladding using an equation-of-state approach

    International Nuclear Information System (INIS)

    Wire, G.L.; Cannon, N.S.; Johnson, G.D.

    1979-01-01

    Correlation of short-term mechanical properties of breeder reactor core component materials play an important role in design and safety analysis. A description of the short-term high strain-rate flow properties for 20% CW 316 SS was developed using a mechanical equation-of-state approach developed by Hart. The stress strain-rate relationship was developed from tensile yield strength data over the temperature range 427-871 0 C. The description, developed for constant structure or hardness, was then combined with simplified work hardening and recovery models to predict response of unirradiated 20% CW 316 SS over loading paths important to breeder reactor cladding. The advantage of the method is that it provides a description of mechanical response under a wide range of loading conditions, yet the formulation is simple in form with a single structure parameter used to describe material structure changes. The method is also shown to be applicable to neutron irradiated 316 SS. This implies that while neutron irradiation can change the hardness and ductility of 316 SS, the basic flow law is unchanged by irradiation. (Auth.)

  2. System size effects on the mechanical response of cohesive-frictional granular ensembles

    Directory of Open Access Journals (Sweden)

    Singh Saurabh

    2017-01-01

    Full Text Available Shear resistance in granular ensembles is a result of interparticle interaction and friction. However, even the presence of small amounts of cohesion between the particles changes the landscape of the mechanical response considerably. Very often such cohesive frictional (c-ϕ granular ensembles are encountered in nature as well as while handling and storage of granular materials in the pharmaceutical, construction and mining industries. Modeling of these c-ϕ materials, especially in engineering applications have relied on the oft-made assumption of a “continua” and have utilized the popular tenets of continuum plasticity theory. We present an experimental investigation on the fundamental mechanics of c-ϕ materials specifically; we investigate if there exists a system size effect and any additional length scales beyond the continuum length scale on their mechanical response. For this purpose, we conduct a series of 1-D compression (UC tests on cylindrical specimens reconstituted in the laboratory with a range of model particle–binder combinations such as sandcement, sand-epoxy, and glass ballotini-epoxy mixtures. Specimens are reconstituted to various diameters ranging from 10 mm to 150 mm (with an aspect ratio of 2 to a predefined packing fraction. In addition to the effect of the type of binder (cement, epoxy and system size, the mean particle size is also varied from 0.5 to 2.5 mm. The peak strength of these materials is significant as it signals the initiation of the cohesive-bond breaking and onset of mobilization of the inter particle frictional resistance. For these model systems, the peak strength is a strong function of the system size of the ensemble as well as the mean particle size. This intriguing observation is counter to the traditional notion of a continuum plastic typical granular ensemble. Microstructure studies in a computed-tomograph have revealed the existence of a web patterned ‘entangled-chain’ like structure

  3. System size effects on the mechanical response of cohesive-frictional granular ensembles

    Science.gov (United States)

    Singh, Saurabh; Kandasami, Ramesh Kannan; Mahendran, Rupesh Kumar; Murthy, Tejas

    2017-06-01

    Shear resistance in granular ensembles is a result of interparticle interaction and friction. However, even the presence of small amounts of cohesion between the particles changes the landscape of the mechanical response considerably. Very often such cohesive frictional (c-ϕ) granular ensembles are encountered in nature as well as while handling and storage of granular materials in the pharmaceutical, construction and mining industries. Modeling of these c-ϕ materials, especially in engineering applications have relied on the oft-made assumption of a "continua" and have utilized the popular tenets of continuum plasticity theory. We present an experimental investigation on the fundamental mechanics of c-ϕ materials specifically; we investigate if there exists a system size effect and any additional length scales beyond the continuum length scale on their mechanical response. For this purpose, we conduct a series of 1-D compression (UC) tests on cylindrical specimens reconstituted in the laboratory with a range of model particle-binder combinations such as sandcement, sand-epoxy, and glass ballotini-epoxy mixtures. Specimens are reconstituted to various diameters ranging from 10 mm to 150 mm (with an aspect ratio of 2) to a predefined packing fraction. In addition to the effect of the type of binder (cement, epoxy) and system size, the mean particle size is also varied from 0.5 to 2.5 mm. The peak strength of these materials is significant as it signals the initiation of the cohesive-bond breaking and onset of mobilization of the inter particle frictional resistance. For these model systems, the peak strength is a strong function of the system size of the ensemble as well as the mean particle size. This intriguing observation is counter to the traditional notion of a continuum plastic typical granular ensemble. Microstructure studies in a computed-tomograph have revealed the existence of a web patterned `entangled-chain' like structure, we argue that this ushers

  4. Ion transport by the amphibian primary ureter

    DEFF Research Database (Denmark)

    Møbjerg, Nadja

    2008-01-01

    putative ion transport mechanisms in the primary ureter of the freshwater amphibian Ambystoma mexicanum (axolotl). Primary ureters isolated from axolotl larvae were perfused in vitro and single cells were impaled across the basal cell membrane with glass microelectrodes. In 42 cells the membrane potential......+] steps from 3 to 20 mmol/l and a hyperpolarization of Vm upon lowering [Na+] from 102 to 2 mmol/l, indicating the presence of luminal K+ and Na+ conductances. This study provides the first functional data on the vertebrate primary ureter. The data show that the primary ureter of axolotl larvae...

  5. Anti-Epidermal Growth Factor Receptor Therapy in Head and Neck Squamous Cell Carcinoma: Focus on Potential Molecular Mechanisms of Drug Resistance

    Science.gov (United States)

    Baay, Marc; Wouters, An; Specenier, Pol; Vermorken, Jan B.; Peeters, Marc; Lardon, Filip

    2013-01-01

    Targeted therapy against the epidermal growth factor receptor (EGFR) is one of the most promising molecular therapeutics for head and neck squamous cell carcinoma (HNSCC). EGFR is overexpressed in a wide range of malignancies, including HNSCC, and initiates important signal transduction pathways in HNSCC carcinogenesis. However, primary and acquired resistance are serious problems and are responsible for low single-agent response rate and tumor recurrence. Therefore, an improved understanding of the molecular mechanisms of resistance to EGFR inhibitors may provide valuable indications to identify biomarkers that can be used clinically to predict response to EGFR blockade and to establish new treatment options to overcome resistance. To date, no predictive biomarker for HNSCC is available in the clinic. Therapeutic resistance to anti-EGFR therapy may arise from mechanisms that can compensate for reduced EGFR signaling and/or mechanisms that can modulate EGFR-dependent signaling. In this review, we will summarize some of these molecular mechanisms and describe strategies to overcome that resistance. PMID:23821327

  6. Primary Nurse - Role Evolution

    Science.gov (United States)

    Mundinger, Mary O'Neil

    1973-01-01

    Primary nursing means that each patient has an individual nurse who is responsible for assessing his nursing needs and planning and evaluating his nursing care. The article describes the advantages and problems connected with this approach to patient care. (AG)

  7. Patients harboring EGFR mutation after primary resistance to crizotinib and response to EGFR-tyrosine kinase inhibitor

    Directory of Open Access Journals (Sweden)

    Wang WX

    2016-01-01

    Full Text Available Wenxian Wang,1 Xiaowen Jiang,1 Zhengbo Song,1,2 Yiping Zhang1,2 1Department of Chemotherapy, Zhejiang Cancer Hospital, 2Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang, People’s Republic of China Abstract: Anaplastic lymphoma kinase (ALK rearrangement lung cancer responds to ALK tyrosine kinase inhibitors. It is known that many cases ultimately acquired resistance to crizotinib. However, a case of primary resistance is rare. We present a case of harboring exon 19 deletion in epidermal growth factor receptor in ALK rearranged lung adenocarcinoma, who experienced a partial tumor response to icotinib after failure with crizotinib therapy and chemotherapy. Considering the partial response, we conclude that it is important to find the cause of resistance to crizotinib. We detected gene mutations with plasma by the next-generation sequencing; the next-generation sequencing demonstrates an attractive system to identify mutations improving the outcome of patients with a deadly disease. Keywords: non-small cell lung cancer, anaplastic lymphoma kinase, crizotinib, epidermal growth factor receptor

  8. A Participatory Model of the Paradox of Primary Care

    Science.gov (United States)

    Homa, Laura; Rose, Johnie; Hovmand, Peter S.; Cherng, Sarah T.; Riolo, Rick L.; Kraus, Alison; Biswas, Anindita; Burgess, Kelly; Aungst, Heide; Stange, Kurt C.; Brown, Kalanthe; Brooks-Terry, Margaret; Dec, Ellen; Jackson, Brigid; Gilliam, Jules; Kikano, George E.; Reichsman, Ann; Schaadt, Debbie; Hilfer, Jamie; Ticknor, Christine; Tyler, Carl V.; Van der Meulen, Anna; Ways, Heather; Weinberger, Richard F.; Williams, Christine

    2015-01-01

    PURPOSE The paradox of primary care is the observation that primary care is associated with apparently low levels of evidence-based care for individual diseases, but systems based on primary care have healthier populations, use fewer resources, and have less health inequality. The purpose of this article is to explore, from a complex systems perspective, mechanisms that might account for the effects of primary care beyond disease-specific care. METHODS In an 8-session, participatory group model-building process, patient, caregiver, and primary care clinician community stakeholders worked with academic investigators to develop and refine an agent-based computer simulation model to test hypotheses about mechanisms by which features of primary care could affect health and health equity. RESULTS In the resulting model, patients are at risk for acute illness, acute life-changing illness, chronic illness, and mental illness. Patients have changeable health behaviors and care-seeking tendencies that relate to their living in advantaged or disadvantaged neighborhoods. There are 2 types of care available to patients: primary and specialty. Primary care in the model is less effective than specialty care in treating single diseases, but it has the ability to treat multiple diseases at once. Primary care also can provide disease prevention visits, help patients improve their health behaviors, refer to specialty care, and develop relationships with patients that cause them to lower their threshold for seeking care. In a model run with primary care features turned off, primary care patients have poorer health. In a model run with all primary care features turned on, their conjoint effect leads to better population health for patients who seek primary care, with the primary care effect being particularly pronounced for patients who are disadvantaged and patients with multiple chronic conditions. Primary care leads to more total health care visits that are due to more disease

  9. Mechanism of Penicillium expansum in response to exogenous nitric oxide based on proteomics analysis.

    Science.gov (United States)

    Lai, Tongfei; Chen, Yong; Li, Boqiang; Qin, Guozheng; Tian, Shiping

    2014-05-30

    Penicillium expansum is an important fungal pathogen, which causes blue mold rot in various fruits and produces a mycotoxin (patulin) with potential damage to public health. Here, we found that nitric oxide (NO) donor could significantly inhibit germinability of P. expansum spores, resulting in lower virulence to apple fruit. Based on two dimension electrophoresis (2-DE) and mass spectrometry (MS) analysis, we identified ten differentially expressed proteins in response to exogenous NO in P. expansum. Among of them, five proteins, such as glutamine synthetase (GS), amidohydrolase, nitrilases, nitric oxide dioxygenase (NOD) and heat shock protein 70, were up-regulated. Others including tetratricopeptide repeat domain, UDP-N-acetylglucosamine pyrophosphorylase, enolase (Eno), heat shock protein 60 and K homology RNA-binding domain were down-regulated. The expression of three genes associated with the identified proteins (GS, NOD, and Eno) was evaluated at the mRNA level by RT-PCR. Our results provide the novel evidence for understanding the mechanism, by which NO regulates growth of P. expansum and its virulence. Crop diseases caused by fungal pathogens lead to huge economic losses every year in the world. Application of chemical fungicides to control diseases brings the concern about food and environmental safety. Screening new antimicrobial compounds and exploring involved mechanisms have great significance to development of new disease management strategies. Nitric oxide (NO), as an important intracellular signaling molecule, has been proved to be involved in many physiological processes and defense responses during plant-pathogen interactions. In this study, we firstly found that NO at high concentration could distinctly delay spore germination and significantly reduce virulence of P. expansum to fruit host, identified some important proteins in response to NO stress and characterized the functions of these proteins. These results provide novel evidence for

  10. Research on Formation Mechanism of Dynamic Response and Residual Stress of Sheet Metal Induced by Laser Shock Wave

    Science.gov (United States)

    Feng, Aixin; Cao, Yupeng; Wang, Heng; Zhang, Zhengang

    2018-01-01

    In order to reveal the quantitative control of the residual stress on the surface of metal materials, the relevant theoretical and experimental studies were carried out to investigate the dynamic response of metal thin plates and the formation mechanism of residual stress induced by laser shock wave. In this paper, the latest research trends on the surface residual stress of laser shock processing technology were elaborated. The main progress of laser shock wave propagation mechanism and dynamic response, laser shock, and surface residual stress were discussed. It is pointed out that the multi-scale characterization of laser and material, surface residual stress and microstructure change is a new hotspot in laser shock strengthening technology.

  11. Cu removal and response mechanisms of periphytic biofilms in a tubular bioreactor.

    Science.gov (United States)

    Ma, Lan; Wang, Fengwu; Yu, Yuanchun; Liu, Junzhuo; Wu, Yonghong

    2018-01-01

    This work studied Cu removal and response mechanisms of periphytic biofilms in a tubular bioreactor. Periphytic biofilms immobilized in a tubular bioreactor were used to remove Cu from wastewater with different Cu concentrations. Results showed that periphytic biofilms had a high removal efficiency (max. 99%) at a hydraulic retention time (HRT) of 12h under initial Cu concentrations of 2.0 and 10.0mgL -1 . Periphyton quickly adapted to Cu stress by regulating the community composition. Species richness, evenness and carbon metabolic diversity of the periphytic community increased when exposed to Cu. Diatoms, green algae, and bacteria (Gammaproteobacteria and Bacteroidia) were the dominant microorganisms and responsible for Cu removal. This study indicates that periphytic biofilms are promising in Cu removal from wastewater due to their strong adaptation capacity to Cu toxicity and also provides valuable information for understanding the relationships between microbial communities and heavy metal stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Nonlinear dynamic analysis of nuclear reactor primary coolant systems

    International Nuclear Information System (INIS)

    Saffell, B.F. Jr.; Macek, R.W.; Thompson, T.R.; Lippert, R.F.

    1979-01-01

    The ADINA computer code is utilized to perform mechanical response analysis of pressurized reactor primary coolant systems subjected to postulated loss-of-coolant accident (LOCA) loadings. Specifically, three plant analyses are performed utilizing the geometric and material nonlinear analysis capabilities of ADINA. Each reactor system finite element model represents the reactor vessel and internals, piping, major components, and component supports in a single coupled model. Material and geometric nonlinear capabilities of the beam and truss elements are employed in the formulation of each finite element model. Loadings applied to each plant for LOCA dynamic analysis include steady-state pressure, dead weight, strain energy release, transient piping hydraulic forces, and reactor vessel cavity pressurization. Representative results are presented with some suggestions for consideration in future ADINA code development

  13. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  14. Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Funda Erol Çipe

    2014-01-01

    Full Text Available Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1 was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases.

  15. Simulation of the Mechanical Response of the 11T Magnet by Means of COMSOL-MpCCI-ANSYS Coupling

    CERN Document Server

    Wilczek, Michal

    2017-01-01

    This report covers the work during my Summer Student internship at CERN as a part of the STEAM group (Simulation of Transient Effects in Accelerator Magnets) in the Technology Department, Machine Protection and Electrical Integrity group. I was responsible for the development of the ANSYS APDL model of the 11T superconducting magnet serving as a proof of concept for magneto-thermo-mechanical co-simulations of quench propagation in COMSOL and ANSYS software. The aforementioned co-simulation estimates the magnetic, thermal, and mechanical response of the magnet during the discharge process, while protected by a recently developed method, called Coupling-Loss Induced Quench (CLIQ). The already existing STEAM framework performs field/circuit coupling of a magneto-thermal field models previously developed by the STEAM. The next task of the group aimed at combining magneto-thermal field solution with the mechanical simulations. Such a coupling is of interest for the High-Luminosity upgrade of the Large Hadron Colli...

  16. Mechanical response of the herniated human abdomen to the placement of different prostheses.

    Science.gov (United States)

    Hernández-Gascón, Belén; Peña, Estefanía; Grasa, Jorge; Pascual, Gemma; Bellón, Juan M; Calvo, Begoña

    2013-05-01

    This paper describes a method designed to model the repaired herniated human abdomen just after surgery and examine its static mechanical response to the maximum intra-abdominal pressure provoked by a physiological movement (standing cough). The model is based on the real geometry of the human abdomen bearing a large incisional hernia with several anatomical structures differentiated by MRI. To analyze the outcome of hernia repair, the surgical procedure was simulated by modeling a prosthesis placed over the hernia. Three surgical meshes with different mechanical properties were considered: an isotropic heavy-weight mesh (Surgipro®), a slightly anisotropic light-weight mesh (Optilene®), and a highly anisotropic medium-weight mesh (Infinit®). Our findings confirm that anisotropic implants need to be positioned such that the most compliant axis of the mesh coincides with the craneo-caudal direction of the body.

  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. Developing a programme theory to explain how primary health care teams learn to respond to intimate partner violence: a realist case-study.

    Science.gov (United States)

    Goicolea, Isabel; Hurtig, Anna-Karin; San Sebastian, Miguel; Vives-Cases, Carmen; Marchal, Bruno

    2015-06-09

    Despite the progress made on policies and programmes to strengthen primary health care teams' response to Intimate Partner Violence, the literature shows that encounters between women exposed to IPV and health-care providers are not always satisfactory, and a number of barriers that prevent individual health-care providers from responding to IPV have been identified. We carried out a realist case study, for which we developed and tested a programme theory that seeks to explain how, why and under which circumstances a primary health care team in Spain learned to respond to IPV. A realist case study design was chosen to allow for an in-depth exploration of the linkages between context, intervention, mechanisms and outcomes as they happen in their natural setting. The first author collected data at the primary health care center La Virgen (pseudonym) through the review of documents, observation and interviews with health systems' managers, team members, women patients, and members of external services. The quality of the IPV case management was assessed with the PREMIS tool. This study found that the health care team at La Virgen has managed 1) to engage a number of staff members in actively responding to IPV, 2) to establish good coordination, mutual support and continuous learning processes related to IPV, 3) to establish adequate internal referrals within La Virgen, and 4) to establish good coordination and referral systems with other services. Team and individual level factors have triggered the capacity and interest in creating spaces for team leaning, team work and therapeutic responses to IPV in La Virgen, although individual motivation strongly affected this mechanism. Regional interventions did not trigger individual and/ or team responses but legitimated the workings of motivated professionals. The primary health care team of La Virgen is involved in a continuous learning process, even as participation in the process varies between professionals. This

  19. Effect of surface loading on the hydro-mechanical response of a tunnel in saturated ground

    Directory of Open Access Journals (Sweden)

    Simon Heru Prassetyo

    2016-09-01

    Full Text Available The design of underground spaces in urban areas must account not only for the current overburden load but also for future surface loads, such as from construction of high-rise buildings above underground structures. In saturated ground, the surface load will generate an additional mechanical response through stress changes and ground displacement, as well as a hydraulic response through pore pressure changes. These hydro-mechanical (H-M changes can severely influence tunnel stability. This paper examines the effect of surface loading on the H-M response of a typical horseshoe-shaped tunnel in saturated ground. Two tunnel models were created in the computer code Fast Lagrangian Analysis of Continua (FLAC. One model represented weak and low permeability ground (stiff clay, and the other represented strong and high permeability ground (weathered granite. Each of the models was run under two liner permeabilities: permeable and impermeable. Two main cases were compared. In Case 1, the surface load was applied 10 years after tunnel construction. In Case 2, the surface load was applied after the steady state pore pressure condition was achieved. The simulation results show that tunnels with impermeable liners experienced the most severe influence from the surface loading, with high pore pressures, large inward displacement around the tunnels, and high bending moments in the liner. In addition, the severity of the response increased toward steady state. This induced H-M response was worse for tunnels in clay than for those in granite. Furthermore, the long-term liner stabilities in Case 1 and Case 2 were similar, indicating that the influence of the length of time between when the tunnel was completed and when the surface load was applied was negligible. These findings suggest that under surface loading, in addition to the ground strength, tunnel stability in saturated ground is largely influenced by liner permeability and the long-term H-M response of

  20. Access to primary care for socioeconomically disadvantaged older people in rural areas: a realist review.

    Science.gov (United States)

    Ford, John A; Wong, Geoff; Jones, Andy P; Steel, Nick

    2016-05-17

    The aim of this review is to identify and understand the contexts that effect access to high-quality primary care for socioeconomically disadvantaged older people in rural areas. A realist review. MEDLINE and EMBASE electronic databases and grey literature (from inception to December 2014). Broad inclusion criteria were used to allow articles which were not specific, but might be relevant to the population of interest to be considered. Studies meeting the inclusion criteria were assessed for rigour and relevance and coded for concepts relating to context, mechanism or outcome. An overarching patient pathway was generated and used as the basis to explore contexts, causal mechanisms and outcomes. 162 articles were included. Most were from the USA or the UK, cross-sectional in design and presented subgroup data by age, rurality or deprivation. From these studies, a patient pathway was generated which included 7 steps (problem identified, decision to seek help, actively seek help, obtain appointment, get to appointment, primary care interaction and outcome). Important contexts were stoicism, education status, expectations of ageing, financial resources, understanding the healthcare system, access to suitable transport, capacity within practice, the booking system and experience of healthcare. Prominent causal mechanisms were health literacy, perceived convenience, patient empowerment and responsiveness of the practice. Socioeconomically disadvantaged older people in rural areas face personal, community and healthcare barriers that limit their access to primary care. Initiatives should be targeted at local contextual factors to help individuals recognise problems, feel welcome, navigate the healthcare system, book appointments easily, access appropriate transport and have sufficient time with professional staff to improve their experience of healthcare; all of which will require dedicated primary care resources. Published by the BMJ Publishing Group Limited. For