Controlled ultrasound-induced blood-brain barrier disruption using passive acoustic emissions monitoring.

Directory of Open Access Journals (Sweden)

Costas D Arvanitis

Full Text Available The ability of ultrasonically-induced oscillations of circulating microbubbles to permeabilize vascular barriers such as the blood-brain barrier (BBB holds great promise for noninvasive targeted drug delivery. A major issue has been a lack of control over the procedure to ensure both safe and effective treatment. Here, we evaluated the use of passively-recorded acoustic emissions as a means to achieve this control. An acoustic emissions monitoring system was constructed and integrated into a clinical transcranial MRI-guided focused ultrasound system. Recordings were analyzed using a spectroscopic method that isolates the acoustic emissions caused by the microbubbles during sonication. This analysis characterized and quantified harmonic oscillations that occur when the BBB is disrupted, and broadband emissions that occur when tissue damage occurs. After validating the system's performance in pilot studies that explored a wide range of exposure levels, the measurements were used to control the ultrasound exposure level during transcranial sonications at 104 volumes over 22 weekly sessions in four macaques. We found that increasing the exposure level until a large harmonic emissions signal was observed was an effective means to ensure BBB disruption without broadband emissions. We had a success rate of 96% in inducing BBB disruption as measured by in contrast-enhanced MRI, and we detected broadband emissions in less than 0.2% of the applied bursts. The magnitude of the harmonic emissions signals was significantly (P<0.001 larger for sonications where BBB disruption was detected, and it correlated with BBB permeabilization as indicated by the magnitude of the MRI signal enhancement after MRI contrast administration (R(2 = 0.78. Overall, the results indicate that harmonic emissions can be a used to control focused ultrasound-induced BBB disruption. These results are promising for clinical translation of this technology.

Perceptual, not memorial, disruption underlies emotion-induced blindness.

Science.gov (United States)

Kennedy, Briana L; Most, Steven B

2012-04-01

Emotion-induced blindness refers to impaired awareness of stimuli appearing in the temporal wake of an emotionally arousing stimulus (S. B. Most, Chun, Widders, & Zald, 2005). In previous emotion-induced blindness experiments, participants withheld target responses until the end of a rapid stream of stimuli, even though each target appeared in the middle of the stream. The resulting interval between the targets' offset and participants' initiation of a response leaves open the possibility that emotion-induced blindness reflects a failure to encode or maintain target information in memory rather than a failure of perception. In the present study, participants engaged in a typical emotion-induced blindness task but initiated a response immediately upon seeing each target. Emotion-induced blindness was nevertheless robust. This suggests that emotion-induced blindness is not attributable to the delay between awareness of a target and the initiation of a response, but rather reflects the disruptive impact of emotional distractors on mechanisms driving conscious perception. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Applying fluorescence correlation spectroscopy to investigate peptide-induced membrane disruption

DEFF Research Database (Denmark)

Kristensen, Kasper; Henriksen, Jonas Rosager; Andresen, Thomas Lars

2017-01-01

to quantify leakage of fluorescent molecules of different sizes from large unilamellar lipid vesicles, thereby providing a tool for estimating the size of peptide-induced membrane disruptions. If fluorescently labeled lipids are incorporated into the membranes of the vesicles, FCS can also be used to obtain...

Disruption prediction at JET

International Nuclear Information System (INIS)

Milani, F.

1998-12-01

The sudden loss of the plasma magnetic confinement, known as disruption, is one of the major issue in a nuclear fusion machine as JET (Joint European Torus). Disruptions pose very serious problems to the safety of the machine. The energy stored in the plasma is released to the machine structure in few milliseconds resulting in forces that at JET reach several Mega Newtons. The problem is even more severe in the nuclear fusion power station where the forces are in the order of one hundred Mega Newtons. The events that occur during a disruption are still not well understood even if some mechanisms that can lead to a disruption have been identified and can be used to predict them. Unfortunately it is always a combination of these events that generates a disruption and therefore it is not possible to use simple algorithms to predict it. This thesis analyses the possibility of using neural network algorithms to predict plasma disruptions in real time. This involves the determination of plasma parameters every few milliseconds. A plasma boundary reconstruction algorithm, XLOC, has been developed in collaboration with Dr. D. O'Brien and Dr. J. Ellis capable of determining the plasma wall/distance every 2 milliseconds. The XLOC output has been used to develop a multilayer perceptron network to determine plasma parameters as l i and q ψ with which a machine operational space has been experimentally defined. If the limits of this operational space are breached the disruption probability increases considerably. Another approach for prediction disruptions is to use neural network classification methods to define the JET operational space. Two methods have been studied. The first method uses a multilayer perceptron network with softmax activation function for the output layer. This method can be used for classifying the input patterns in various classes. In this case the plasma input patterns have been divided between disrupting and safe patterns, giving the possibility of

Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

Energy Technology Data Exchange (ETDEWEB)

Gao, Fu [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Chambon, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104, INSERM U596, ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg (France); Tellides, George [Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT (United States); Kong, Wei [Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing (China); Zhang, Xiaoming, E-mail: rmygxgwk@163.com [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Li, Wei [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China)

2014-11-07

Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

Science.gov (United States)

Busschaert, Nathalie; Park, Seong-Hyun; Baek, Kyung-Hwa; Choi, Yoon Pyo; Park, Jinhong; Howe, Ethan N. W.; Hiscock, Jennifer R.; Karagiannidis, Louise E.; Marques, Igor; Félix, Vítor; Namkung, Wan; Sessler, Jonathan L.; Gale, Philip A.; Shin, Injae

2017-07-01

Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism.

Directory of Open Access Journals (Sweden)

Xiling Liu

2016-09-01

Full Text Available Cognitive defects in autism spectrum disorder (ASD include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans.

Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

Science.gov (United States)

Jiang, Xi; Hu, Haiyang; Guijarro, Patricia; Mitchell, Amanda; Ely, John J.; Sherwood, Chet C.; Hof, Patrick R.; Qiu, Zilong; Pääbo, Svante; Akbarian, Schahram; Khaitovich, Philipp

2016-01-01

Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. PMID:27685936

Withaferin A disrupts ubiquitin-based NEMO reorganization induced by canonical NF-κB signaling

Energy Technology Data Exchange (ETDEWEB)

Jackson, Shawn S. [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Medical Scientist Training Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Cellular and Molecular Biology Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Oberley, Christopher [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Hooper, Christopher P. [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Cellular and Molecular Biology Program, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Grindle, Kreg [Department of Medicine, Division of Hematology and Oncology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); Wuerzberger-Davis, Shelly [McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, 6159 Wisconsin Institute for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (United States); Wolff, Jared [Department of Medicine, Division of Hematology and Oncology, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705 (United States); and others

2015-02-01

The NF-κB family of transcription factors regulates numerous cellular processes, including cell proliferation and survival responses. The constitutive activation of NF-κB has also emerged as an important oncogenic driver in many malignancies, such as activated B-cell like diffuse large B cell lymphoma, among others. In this study, we investigated the impact and mechanisms of action of Withaferin A, a naturally produced steroidal lactone, against both signal-inducible as well as constitutive NF-κB activities. We found that Withaferin A is a robust inhibitor of canonical and constitutive NF-κB activities, leading to apoptosis of certain lymphoma lines. In the canonical pathway induced by TNF, Withaferin A did not disrupt RIP1 polyubiquitination or NEMO–IKKβ interaction and was a poor direct IKKβ inhibitor, but prevented the formation of TNF-induced NEMO foci which colocalized with TNF ligand. While GFP-NEMO efficiently formed TNF-induced foci, a GFP-NEMO{sup Y308S} mutant that is defective in binding to polyubiquitin chains did not form foci. Our study reveals that Withaferin A is a novel type of IKK inhibitor which acts by disrupting NEMO reorganization into ubiquitin-based signaling structures in vivo. - Highlights: • Withaferin A, a NF-κB inhibitor, disrupts signaling induced NEMO localization, a novel point of inhibition. • NEMO can be localized to distinct signaling foci after treatment with TNF. • ABC-type DLCBL cells can be sensitized to apoptosis after treatment with Withaferin A.

Blood-brain barrier disruption induced by diagnostic ultrasound combined with microbubbles in mice.

Science.gov (United States)

Zhao, Bingxia; Chen, Yihan; Liu, Jinfeng; Zhang, Li; Wang, Jing; Yang, Yali; Lv, Qing; Xie, Mingxing

2018-01-12

To investigate the effects of the microbubble (MB) dose, mechanism index (MI) and sonication duration on blood-brain barrier (BBB) disruption induced by diagnostic ultrasound combined with MBs as well as to investigate the potential molecular mechanism. The extent of BBB disruption increased with MB dose, MI and sonication duration. A relatively larger extent of BBB disruption associated with minimal tissue damage was achieved by an appropriate MB dose and ultrasound exposure parameters with diagnostic ultrasound. Decreased expression of ZO-1, occludin and claudin-5 were correlated with disruption of the BBB, as confirmed by paracellular passage of the tracer lanthanum nitrate into the brain parenchyma after BBB disruption. These findings indicated that this technique is a promising tool for promoting brain delivery of diagnostic and therapeutic agents in the diagnosis and treatment of brain diseases. The extent of BBB disruption was qualitatively assessed by Evans blue (EB) staining and quantitatively analyzed by an EB extravasation measurement. A histological examination was performed to evaluate tissue damage. Expression of tight junction (TJ) related proteins ZO-1, occludin and claudin-5 was determined by western blotting analysis and immunohistofluorescence. Transmission electron microscopy was performed to observe ultrastructure changes of TJs after BBB disruption.

Disruptive coloration in woodland camouflage: evaluation of camouflage effectiveness due to minor disruptive patches

Science.gov (United States)

Selj, Gorm K.; Heinrich, Daniela H.

2016-10-01

We present results from an observer based photosimulation study of generic camouflage patterns, intended for military uniforms, where three near-identical patterns have been compared. All the patterns were prepared with similar effective color, but were different in how the individual pattern patches were distributed throughout the target. We did this in order to test if high contrast (black) patches along the outline of the target would enhance the survivability when exposed to human observers. In the recent years it has been shown that disruptive coloration in the form of high contrast patches are capable of disturbing an observer by creating false edges of the target and consequently enhance target survivability. This effect has been shown in different forms in the Animal Kingdom, but not to the same extent in camouflaged military targets. The three patterns in this study were i) with no disruptive preference, ii) with a disruptive patch along the outline of the head and iii) with a disruptive patch on the outline of one of the shoulders. We used a high number of human observers to assess the three targets in 16 natural (woodland) backgrounds by showing images of one of the targets at the time on a high definition pc screen. We found that the two patterns that were thought to have a minor disruptive preference to the remaining pattern were more difficult to detect in some (though not all) of the 16 scenes and were also better in overall performance when all the scenes were accounted for.

The Impact of Operating Room Layout on Circulating Nurse's Work Patterns and Flow Disruptions: A Behavioral Mapping Study.

Science.gov (United States)

Bayramzadeh, Sara; Joseph, Anjali; San, Dee; Khoshkenar, Amin; Taaffe, Kevin; Jafarifiroozabadi, Roxana; Neyens, David M

2018-01-01

To assess how the adjacencies of functionally different areas within operating rooms (ORs) can influence the circulating nurse's (CN) workflow patterns and disruptions. The CN plays a significant role in promoting patient safety during surgical procedures by observing, monitoring, and managing potential threats at and around the surgical field. Their work requires constant movement to different parts of the OR to support team members. The layout of the OR and crowded and cluttered environment might impact the CN's workflow and cause disruptions during the surgery. A convenience sample of 25 surgeries were video recorded and thematically coded for CN's activities, locations, and flow disruptions. The OR layout was categorized into transitional zones and functional zones (workstations, supply zones, support zones, and sterile areas around the surgical table). CN's activities were classified into patient-, equipment-, material-, and information-related activities. Flow disruptions included those related to environmental hazards and layout. The CN traveled through multiple zones during 91% of the activities. The CN's workstation acted as a main hub from which the CN made frequent trips to both sides of the surgical table, the foot of the OR table, supply zones, and support zones. Transitional zones accounted for 58.3% of all flow disruption that the CN was involved in whereas 28% occurred in areas surrounding the OR bed. The similarity of the movement and flow disruption patterns, despite variations in OR layout, highlighted the adjacencies required between major zones that CNs regularly visit. These optimum adjacencies should be considered while designing ORs such that they are more efficient and safer.

Disrupting the memory of places induced by drugs of abuse weakens motivational withdrawal in a context-dependent manner.

Science.gov (United States)

Taubenfeld, Stephen M; Muravieva, Elizaveta V; Garcia-Osta, Ana; Alberini, Cristina M

2010-07-06

Addicts repeatedly relapse to drug seeking even after years of abstinence, and this behavior is frequently induced by the recall of memories of the rewarding effects of the drug. Established memories, including those induced by drugs of abuse, can become transiently fragile if reactivated, and during this labile phase, known as reconsolidation, can be persistently disrupted. Here we show that, in rats, a morphine-induced place preference (mCPP) memory is linked to context-dependent withdrawal as disrupting the reconsolidation of the memory leads to a significant reduction of withdrawal evoked in the same context. Moreover, the hippocampus plays a critical role in linking the place preference memory with the context-conditioned withdrawal, as disrupting hippocampal protein synthesis and cAMP-dependent-protein kinase A after the reactivation of mCPP significantly weakens the withdrawal. Hence, targeting memories induced by drugs may represent an important strategy for attenuating context-conditioned withdrawal and therefore subsequent relapse in opiate addicts.

Tributyltin induces disruption of microfilament in HL7702 cells via MAPK-mediated hyperphosphorylation of VASP.

Science.gov (United States)

Tu, Wei-Wei; Ji, Lin-Dan; Qian, Hai-Xia; Zhou, Mi; Zhao, Jin-Shun; Xu, Jin

2016-11-01

Tributyltin (TBT) has been widely used for various industrial purposes, and it has toxic effects on multiple organs and tissues. Previous studies have found that TBT could induce cytoskeletal disruption, especially of the actin filaments. However, the underlying mechanisms remain unclear. The aim of the present study was to determine whether TBT could induce microfilament disruption using HL7702 cells and then to assess for the total levels of various microfilament-associated proteins; finally, the involvement of the MAPK pathway was investigated. The results showed that after TBT treatment, F-actin began to depolymerize and lost its characteristic filamentous structure. The protein levels of Ezrin and Cofilin remained unchanged, the actin-related protein (ARP) 2/3 levels decreased slightly, and the vasodilator-stimulated phosphoprotein (VASP) decreased dramatically. However, the phosphorylation levels of VASP increased 2.5-fold, and the ratio of phosphorylated-VASP/unphosphorylated-VASP increased 31-fold. The mitogen-activated protein kinases (MAPKs) ERK and JNK were discovered to be activated. Inhibition of ERK and JNK not only largely diminished the TBT-induced hyperphosphorylation of VASP but also recovered the cellular morphology and rescued the cells from death. In summary, this study demonstrates that TBT-induced disruption of actin filaments is caused by the hyperphosphorylation of VASP through MAPK pathways. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1530-1538, 2016. © 2015 Wiley Periodicals, Inc.

Modeling bubble dynamics and radical kinetics in ultrasound induced microalgal cell disruption.

Science.gov (United States)

Wang, Meng; Yuan, Wenqiao

2016-01-01

Microalgal cell disruption induced by acoustic cavitation was simulated through solving the bubble dynamics in an acoustical field and their radial kinetics (chemical kinetics of radical species) occurring in the bubble during its oscillation, as well as calculating the bubble wall pressure at the collapse point. Modeling results indicated that increasing ultrasonic intensity led to a substantial increase in the number of bubbles formed during acoustic cavitation, however, the pressure generated when the bubbles collapsed decreased. Therefore, cumulative collapse pressure (CCP) of bubbles was used to quantify acoustic disruption of a freshwater alga, Scenedesmus dimorphus, and a marine alga, Nannochloropsis oculata and compare with experimental results. The strong correlations between CCP and the intracellular lipid fluorescence density, chlorophyll-a fluorescence density, and cell particle/debris concentration were found, which suggests that the developed models could accurately predict acoustic cell disruption, and can be utilized in the scale up and optimization of the process. Copyright © 2015 Elsevier B.V. All rights reserved.

Femtosecond laser-induced herringbone patterns

Science.gov (United States)

Garcell, Erik M.; Lam, Billy; Guo, Chunlei

2018-06-01

Femtosecond laser-induced herringbone patterns are formed on copper (Cu). These novel periodic structures are created following s-polarized, large incident angle, femtosecond laser pulses. Forming as slanted and axially symmetric laser-induced periodic surface structures along the side walls of ablated channels, the result is a series of v-shaped structures that resemble a herringbone pattern. Fluence mapping, incident angle studies, as well as polarization studies have been conducted and provide a clear understanding of this new structure.

Mast cell chymase induces smooth muscle cell apoptosis by disrupting NF-κB-mediated survival signaling

International Nuclear Information System (INIS)

Leskinen, Markus J.; Heikkilae, Hanna M.; Speer, Mei Y.; Hakala, Jukka K.; Laine, Mika; Kovanen, Petri T.; Lindstedt, Ken A.

2006-01-01

Chymase released from activated mast cells induces apoptosis of vascular smooth muscle cells (SMCs) in vitro by degrading the pericellular matrix component fibronectin, so causing disruption of focal adhesion complexes and Akt dephosphorylation, which are necessary for cell adhesion and survival. However, the molecular mechanisms of chymase-mediated apoptosis downstream of Akt have remained elusive. Here, we show by means of RT-PCR, Western blotting, EMSA, immunocytochemistry and confocal microscopy, that chymase induces SMC apoptosis by disrupting NF-κB-mediated survival signaling. Following chymase treatment, the translocation of active NF-κB/p65 to the nucleus was partly abolished and the amount of nuclear p65 was reduced. Pretreatment of SMCs with chymase also inhibited LPS- and IL-1β-induced nuclear translocation of p65. The chymase-induced degradation of p65 was mediated by active caspases. Loss of NF-κB-mediated transactivation resulted in downregulation of bcl-2 mRNA and protein expression, leading to mitochondrial swelling and release of cytochrome c. The apoptotic process involved activation of both caspase 9 and caspase 8. The results reveal that, by disrupting the NF-κB-mediated survival-signaling pathway, activated chymase-secreting mast cells can mediate apoptosis of cultured arterial SMCs. Since activated mast cells colocalize with apoptotic SMCs in vulnerable areas of human atherosclerotic plaques, they may participate in the weakening and rupture of atherosclerotic plaques

Effects of sigma(1) receptor ligand, MS-377 on apomorphine- or phencyclidine-induced disruption of prepulse inhibition of acoustic startle in rats.

Science.gov (United States)

Yamada, S; Yamauchi, K; Hisatomi, S; Annoh, N; Tanaka, M

2000-08-25

To evaluate the antipsychotic property of a sigma(1) receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-¿4-(2-methoxyethyl)piperazin-1-yl¿ methyl-2-pyrrolidinone-L-tartrate (MS-377), an antagonistic effect of MS-377 on the disruption of prepulse inhibition (PPI) of the acoustic startle by apomorphine or phencyclidine (PCP) was investigated in rats. MS-377 antagonized the PCP-induced disruption of PPI. The ED(50) value of MS-377 for this effect was 0.66 mg/kg. In contrast, apomorphine-induced disruption of PPI was not attenuated by MS-377. These data indicate that the PCP-induced disruption of PPI in rats would be, at least partially, mediated by sigma receptors and MS-377 could be a novel anti-psychotic agent with clinical efficacy for the sensorimotor-gating deficit in schizophrenia.

Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice

Energy Technology Data Exchange (ETDEWEB)

Farfán-García, E.D.; Pérez-Rodríguez, M. [Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México (Mexico); Espinosa-García, C. [Departamento de Biología de la Reproducción, Universidad Autónoma Metropolitana (UAM), 09310 Ciudad de México (Mexico); Castillo-Mendieta, N.T.; Maldonado-Castro, M.; Querejeta, E.; Trujillo-Ferrara, J.G. [Academias de Fisiología Humana, Bioquímica y Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, 11340 Ciudad de México (Mexico); and others

2016-09-15

The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥ 200 mg/kg, and involving granular cell damage at doses of 400 mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system. - Highlights: • Intraperitoneal 3-thienylboronic acid (3TB) induces tremor in CD1 or C57BL6 mice. • Injury on CNS as well as motor disruption is dose-dependent. • Damage is greater in basal ganglia than in cerebellum or motor cortex. • The DMSO as vehicle plays a key role in the induced effect. • Motor disruption seems to involve basal ganglia and cerebellum damage.

Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic acid in mice

International Nuclear Information System (INIS)

Farfán-García, E.D.; Pérez-Rodríguez, M.; Espinosa-García, C.; Castillo-Mendieta, N.T.; Maldonado-Castro, M.; Querejeta, E.; Trujillo-Ferrara, J.G.

2016-01-01

The scarcity of studies on boron containing compounds (BCC) in the medicinal field is gradually being remedied. Efforts have been made to explore the effects of BCCs due to the properties that boron confers to molecules. Research has shown that the safety of some BCCs is similar to that found for boron-free compounds (judging from the acute toxicological evaluation). However, it has been observed that the administration of 3-thienylboronic acid (3TB) induced motor disruption in CD1 mice. In the current contribution we studied in deeper form the disruption of motor performance produced by the intraperitoneal administration of 3TB in mice from two strains (CD1 and C57BL6). Disruption of motor activity was dependent not only on the dose of 3TB administered, but also on the DMSO concentration in the vehicle. The ability of 3TB to enter the Central Nervous System (CNS) was evidenced by Raman spectroscopy as well as morphological effects on the CNS, such as loss of neurons yielding biased injury to the substantia nigra and striatum at doses ≥ 200 mg/kg, and involving granular cell damage at doses of 400 mg/kg but less injury in the motor cortex. Our work acquaints about the use of this compound in drug design, but the interesting profile as neurotoxic agent invite us to study it regarding the damage on the motor system. - Highlights: • Intraperitoneal 3-thienylboronic acid (3TB) induces tremor in CD1 or C57BL6 mice. • Injury on CNS as well as motor disruption is dose-dependent. • Damage is greater in basal ganglia than in cerebellum or motor cortex. • The DMSO as vehicle plays a key role in the induced effect. • Motor disruption seems to involve basal ganglia and cerebellum damage.

Ionizing radiation induces heritable disruption of epithelial cell interactions

Science.gov (United States)

Park, Catherine C.; Henshall-Powell, Rhonda L.; Erickson, Anna C.; Talhouk, Rabih; Parvin, Bahram; Bissell, Mina J.; Barcellos-Hoff, Mary Helen; Chatterjee, A. (Principal Investigator)

2003-01-01

Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. As a consequence, we have proposed that an additional factor contributing to IR carcinogenesis is the potential disruption of critical constraints that are imposed by normal cell interactions. To test this hypothesis, we asked whether IR affected the ability of nonmalignant human mammary epithelial cells (HMEC) to undergo tissue-specific morphogenesis in culture by using confocal microscopy and imaging bioinformatics. We found that irradiated single HMEC gave rise to colonies exhibiting decreased localization of E-cadherin, beta-catenin, and connexin-43, proteins necessary for the establishment of polarity and communication. Severely compromised acinar organization was manifested by the majority of irradiated HMEC progeny as quantified by image analysis. Disrupted cell-cell communication, aberrant cell-extracellular matrix interactions, and loss of tissue-specific architecture observed in the daughters of irradiated HMEC are characteristic of neoplastic progression. These data point to a heritable, nonmutational mechanism whereby IR compromises cell polarity and multicellular organization.

Cephalopod dynamic camouflage: bridging the continuum between background matching and disruptive coloration

Science.gov (United States)

Hanlon, R.T.; Chiao, C.-C.; Mäthger, L.M.; Barbosa, A.; Buresch, K.C.; Chubb, C.

2008-01-01

Individual cuttlefish, octopus and squid have the versatile capability to use body patterns for background matching and disruptive coloration. We define—qualitatively and quantitatively—the chief characteristics of the three major body pattern types used for camouflage by cephalopods: uniform and mottle patterns for background matching, and disruptive patterns that primarily enhance disruptiveness but aid background matching as well. There is great variation within each of the three body pattern types, but by defining their chief characteristics we lay the groundwork to test camouflage concepts by correlating background statistics with those of the body pattern. We describe at least three ways in which background matching can be achieved in cephalopods. Disruptive patterns in cuttlefish possess all four of the basic components of ‘disruptiveness’, supporting Cott's hypotheses, and we provide field examples of disruptive coloration in which the body pattern contrast exceeds that of the immediate surrounds. Based upon laboratory testing as well as thousands of images of camouflaged cephalopods in the field (a sample is provided on a web archive), we note that size, contrast and edges of background objects are key visual cues that guide cephalopod camouflage patterning. Mottle and disruptive patterns are frequently mixed, suggesting that background matching and disruptive mechanisms are often used in the same pattern. PMID:19008200

PMA synergistically enhances apicularen A-induced cytotoxicity by disrupting microtubule networks in HeLa cells

International Nuclear Information System (INIS)

Seo, Kang-Sik; Hwang, Byung-Doo; Kim, Jong-Seok; Park, Ji-Hoon; Song, Kyoung-Sub; Yun, Eun-Jin; Park, Jong-Il; Kweon, Gi Ryang; Yoon, Wan-Hee; Lim, Kyu

2014-01-01

Combination therapy is key to improving cancer treatment efficacy. Phorbol 12-myristate 13-acetate (PMA), a well-known PKC activator, increases the cytotoxicity of several anticancer drugs. Apicularen A induces cytotoxicity in tumor cells through disrupting microtubule networks by tubulin down-regulation. In this study, we examined whether PMA increases apicularen A-induced cytotoxicity in HeLa cells. Cell viability was examined by thiazolyl blue tetrazolium (MTT) assays. To investigate apoptotic potential of apicularen A, DNA fragmentation assays were performed followed by extracting genomic DNA, and caspase-3 activity assays were performed by fluorescence assays using fluorogenic substrate. The cell cycle distribution induced by combination with PMA and apicularen A was examined by flow cytometry after staining with propidium iodide (PI). The expression levels of target proteins were measured by Western blotting analysis using specific antibodies, and α-tubulin mRNA levels were assessed by reverse transcription polymerase chain reaction (RT-PCR). To examine the effect of combination of PMA and apicularen A on the microtubule architecture, α-tubulin protein and nuclei were visualized by immunofluorescence staining using an anti-α-tubulin antibody and PI, respectively. We found that apicularen A induced caspase-dependent apoptosis in HeLa cells. PMA synergistically increased cytotoxicity and apoptotic sub-G 1 population induced by apicularen A. These effects were completely blocked by the PKC inhibitors Ro31-8220 and Go6983, while caspase inhibition by Z-VAD-fmk did not prevent cytotoxicity. RNA interference using siRNA against PKCα, but not PKCβ and PKCγ, inhibited cytotoxicity induced by combination PMA and apicularen A. PMA increased the apicularen A-induced disruption of microtubule networks by further decreasing α- and β-tubulin protein levels in a PKC-dependent manner. These results suggest that the synergy between PMA and apicularen A is involved by

Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

Science.gov (United States)

Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

2008-03-01

Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

Respiratory Patterns in Students Enrolled in Schools for Disruptive Behaviour before, during, and after "Yoga Nidra" Relaxation

Science.gov (United States)

Jensen, P. S.; Stevens, P. J.; Kenny, D. T.

2012-01-01

This study investigated the effects of one session of "Yoga Nidra" (relaxation technique) on the breathing patterns/respiratory effort in the thoracic and abdominal chest regions of boys with disruptive behaviour using a Respiratory Inductive Plethysmography (RIP). The participants (n = 7) were aged 10-15 years and attending NSW, Department of…

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

Science.gov (United States)

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-02-24

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

Inhibition of autophagy enhances DNA damage-induced apoptosis by disrupting CHK1-dependent S phase arrest

Energy Technology Data Exchange (ETDEWEB)

Liou, Jong-Shian; Wu, Yi-Chen; Yen, Wen-Yen; Tang, Yu-Shuan [Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, ROC (China); Kakadiya, Rajesh B.; Su, Tsann-Long [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, ROC (China); Yih, Ling-Huei, E-mail: lhyih@gate.sinica.edu.tw [Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan, ROC (China)

2014-08-01

DNA damage has been shown to induce autophagy, but the role of autophagy in the DNA damage response and cell fate is not fully understood. BO-1012, a bifunctional alkylating derivative of 3a-aza-cyclopenta[a]indene, is a potent DNA interstrand cross-linking agent with anticancer activity. In this study, BO-1012 was found to reduce DNA synthesis, inhibit S phase progression, and induce phosphorylation of histone H2AX on serine 139 (γH2AX) exclusively in S phase cells. Both CHK1 and CHK2 were phosphorylated in response to BO-1012 treatment, but only depletion of CHK1, but not CHK2, impaired BO-1012-induced S phase arrest and facilitated the entry of γH2AX-positive cells into G2 phase. CHK1 depletion also significantly enhanced BO-1012-induced cell death and apoptosis. These results indicate that BO-1012-induced S phase arrest is a CHK1-dependent pro-survival response. BO-1012 also resulted in marked induction of acidic vesicular organelle (AVO) formation and microtubule-associated protein 1 light chain 3 (LC3) processing and redistribution, features characteristic of autophagy. Depletion of ATG7 or co-treatment of cells with BO-1012 and either 3-methyladenine or bafilomycin A1, two inhibitors of autophagy, not only reduced CHK1 phosphorylation and disrupted S phase arrest, but also increased cleavage of caspase-9 and PARP, and cell death. These results suggest that cells initiate S phase arrest and autophagy as pro-survival responses to BO-1012-induced DNA damage, and that suppression of autophagy enhances BO-1012-induced apoptosis via disruption of CHK1-dependent S phase arrest. - Highlights: • Autophagy inhibitors enhanced the cytotoxicity of a DNA alkylating agent, BO-1012. • BO-1012-induced S phase arrest was a CHK1-dependent pro-survival response. • Autophagy inhibition enhanced BO-1012 cytotoxicity via disrupting the S phase arrest.

Disruption of Circadian Rhythms by Light During Day and Night.

Science.gov (United States)

Figueiro, Mariana G

2017-06-01

This study aims to discuss possible reasons why research to date has not forged direct links between light at night, acute melatonin suppression or circadian disruption, and risks for disease. Data suggest that irregular light-dark patterns or light exposures at the wrong circadian time can lead to circadian disruption and disease risks. However, there remains an urgent need to: (1) specify light stimulus in terms of circadian rather than visual response; (2) when translating research from animals to humans, consider species-specific spectral and absolute sensitivities to light; (3) relate the characteristics of photometric measurement of light at night to the operational characteristics of the circadian system; and (4) examine how humans may be experiencing too little daytime light, not just too much light at night. To understand the health effects of light-induced circadian disruption, we need to measure and control light stimulus during the day and at night.

Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

Science.gov (United States)

Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

2017-11-01

Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

Hydrogeologic effects of natural disruptive events on nuclear waste repositories

International Nuclear Information System (INIS)

Davis, S.N.

1980-06-01

Some possible hydrogeologic effects of disruptive events that may affect repositories for nuclear waste are described. A very large number of combinations of natural events can be imagined, but only those events which are judged to be most probable are covered. Waste-induced effects are not considered. The disruptive events discussed above are placed into four geologic settings. Although the geology is not specific to given repository sites that have been considered by other agencies, the geology has been generalized from actual field data and is, therefore, considered to be physically reasonable. The geologic settings considered are: (1) interior salt domes of the Gulf Coast, (2) bedded salt of southeastern New Mexico, (3) argillaceous rocks of southern Nevanda, and (4) granitic stocks of the Basin and Range Province. Log-normal distributions of permeabilities of rock units are given for each region. Chapters are devoted to: poresity and permeability of natural materials, regional flow patterns, disruptive events (faulting, dissolution of rock forming minerals, fracturing from various causes, rapid changes of hydraulic regimen); possible hydrologic effects of disruptive events; and hydraulic fracturing

Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption.

Directory of Open Access Journals (Sweden)

Michelle Lajko

Full Text Available Bronchopulmonary dysplasia (BPD is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR, shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P0 to P14 to model BPD, then allowed to recover in room air for 1 (P15, 7 (P21, or 14 days (P28. We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80 and lymphocytes (CD45R. Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment.

Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B1

International Nuclear Information System (INIS)

Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S.; Swanevelder, Sonja

2004-01-01

In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B 1 (FB 1 ) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB 1 containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB 1 dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB 1 treatment in the control rats was significantly (P 1 initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB 1 treatment, the initiation effected by FB 1 was less (P 1 initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P 1 treatment. Although, the FB 1 -induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

Protective effect of taurine on the light-induced disruption of isolated frog rod outer segments

International Nuclear Information System (INIS)

Pasantes-Morales, H.; Ademe, R.M.; Quesada, O.

1981-01-01

Isolated frog rod outer segments (ROS) incubated in a Krebs-bicarbonate medium, and illuminated for 2 h, show a profound alteration in their structure. This is characterized by distention of discs, vesiculation, and a marked swelling. The light-induced ROS disruption requires the presence of bicarbonate and sodium chloride. Replacement of bicarbonate by TRIS or HEPES protects ROS structure. Also, substitution of sodium chloride by sucrose or choline chloride maintains unaltered the ROS structure. Deletion of calcium, magnesium, or phosphate does not modify the effect produced by illumination. An increased accumulation of labeled bicarbonate and tritiated water is observed in illuminated ROS, as compared with controls in the dark. The presence of taurine, GABA, or glycine, at concentrations of 5-25 mM, effectively counteracts the light-induced ROS disruption. Taurine (25 mM) reduces labeled bicarbonate and tritiated water levels to those observed in the dark incubated ROS

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus.

Science.gov (United States)

Pérez-Hernández, Mercedes; Fernández-Valle, María Encarnación; Rubio-Araiz, Ana; Vidal, Rebeca; Gutiérrez-López, María Dolores; O'Shea, Esther; Colado, María Isabel

2017-05-15

The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X 7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats. We also evaluated the ability of the MMP-9 inhibitor, SB-3CT (25 mg/kg, i.p.), to prevent these changes in order to validate the involvement of MMP-9 activation in MDMA-induced BBB disruption. The results show that MDMA produces edema of short duration temporally associated with changes in AQP4 expression and a reduction in claudin-5 expression, changes which are prevented by SB-3CT. In addition, MDMA induces a short-term increase in both tPA activity and expression, a serine-protease which is involved in BBB disruption and upregulation of MMP-9 expression. In conclusion, this study provides evidence enough to conclude that MDMA induces edema of short duration due to BBB disruption mediated by MMP-9 activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

Energy Technology Data Exchange (ETDEWEB)

Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

2015-09-15

Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

International Nuclear Information System (INIS)

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-01-01

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues

Disruptions in the TFTR tokamak

International Nuclear Information System (INIS)

Janos, A.; Fredrickson, E.D.; McGuire, K.; Batha, S.H.; Bell, M.G.; Bitter, M.; Budny, R.; Bush, C.E.; Efthimion, P.C.; Hawryluk, R.J.; Hill, K.W.; Hosea, J.; Jobes, F.C.; Johnson, D.W.; Levinton, F.; Mansfield, D.; Meade, D.; Medley, S.S.; Monticello, D.; Mueller, D.; Nagayama, Y.; Owens, D.K.; Park, H.; Park, W.; Post, D.E.; Schivell, J.; Strachan, J.D.; Taylor, G.; Ulrickson, M.; Goeler, S. von; Wilfrid, E.; Wong, K.L.; Yamada, M.; Young, K.M.; Zarnstorff, M.C.; Zweben, S.J.; Drake, J.F.; Kleva, R.G.; Fleischmann, H.H.

1993-03-01

For a successful reactor, it will be useful to predict the occurrence of disruptions and to understand disruption effects including how a plasma disrupts onto the wall and how reproducibly it does so. Studies of disruptions on TFTR at both high-β pol and high-density have shown that, in both types, a fast growing m/n=1/1 mode plays an important role. In highdensity disruptions, a newly observed fast m/n = 1/1 mode occurs early in the thermal decay phase. For the first time in TFTR q-profile measurements just prior to disruptions have been made. Experimental studies of heat deposition patterns on the first wall of TFTR due to disruptions have provided information on MHD phenomena prior to or during the disruption, how the energy is released to the wall, and the reproducibility of the heat loads from disruptions. This information is important in the design of future devices such as ITER. Several new processes of runaway electron generation are theoretically suggested and their application to TFTR and ITER is considered, together with a preliminary assessment of x-ray data from runaways generated during disruptions

A camera-phone based study reveals erratic eating pattern and disrupted daily eating-fasting cycle among adults in India.

Directory of Open Access Journals (Sweden)

Neelu Jain Gupta

Full Text Available The daily rhythm of feeding-fasting and meal-timing are emerging as important determinants of health. Circadian rhythm research in animal models and retrospective analyses of human nutrition data have shown that reduced length of overnight fasting or increased late night eating increases risk for metabolic diseases including obesity and diabetes. However, the daily rhythm in eating pattern in humans is rarely measured. Traditional methods to collect nutrition information through food diary and food log pay little attention to the timing of eating which may also change from day to day. We adopted a novel cell-phone based approach to longitudinally record all events of food and beverage intake in adults. In a feasibility study daily food-eating patterns of 93 healthy individuals were recorded for 21 days using camera phones. Analysis of the daily eating patterns of these individuals indicates deviation from conventional assumption that people eat three meals-a-day within a 12 h interval. We found that eating events are widespread throughout the day, with 30% consumed in evening and late night hours. There was little difference in eating pattern between weekdays and weekends. In this cohort more than 50% of people spread their caloric intake events over 15 h or longer. One decile of the cohort who were spouses of shift-workers or had flexible work schedule spread their caloric intake over 20 h. Although the nutrition quality and diversity of food consumed is different between South-East Asian and Western countries, such overall disruption of daily eating-fasting rhythm is similar. Therefore, in view of hypothesis that disrupted daily eating pattern may contribute to the global increase in metabolic diseases and modification of daily eating pattern is a potential modifiable behavior to contain these diseases, monitoring eating pattern is an important aspect of lifestyle.

A camera-phone based study reveals erratic eating pattern and disrupted daily eating-fasting cycle among adults in India.

Science.gov (United States)

Gupta, Neelu Jain; Kumar, Vinod; Panda, Satchidananda

2017-01-01

The daily rhythm of feeding-fasting and meal-timing are emerging as important determinants of health. Circadian rhythm research in animal models and retrospective analyses of human nutrition data have shown that reduced length of overnight fasting or increased late night eating increases risk for metabolic diseases including obesity and diabetes. However, the daily rhythm in eating pattern in humans is rarely measured. Traditional methods to collect nutrition information through food diary and food log pay little attention to the timing of eating which may also change from day to day. We adopted a novel cell-phone based approach to longitudinally record all events of food and beverage intake in adults. In a feasibility study daily food-eating patterns of 93 healthy individuals were recorded for 21 days using camera phones. Analysis of the daily eating patterns of these individuals indicates deviation from conventional assumption that people eat three meals-a-day within a 12 h interval. We found that eating events are widespread throughout the day, with 30% consumed in evening and late night hours. There was little difference in eating pattern between weekdays and weekends. In this cohort more than 50% of people spread their caloric intake events over 15 h or longer. One decile of the cohort who were spouses of shift-workers or had flexible work schedule spread their caloric intake over 20 h. Although the nutrition quality and diversity of food consumed is different between South-East Asian and Western countries, such overall disruption of daily eating-fasting rhythm is similar. Therefore, in view of hypothesis that disrupted daily eating pattern may contribute to the global increase in metabolic diseases and modification of daily eating pattern is a potential modifiable behavior to contain these diseases, monitoring eating pattern is an important aspect of lifestyle.

Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.

Science.gov (United States)

Kamat, Pradip K; Kyles, Philip; Kalani, Anuradha; Tyagi, Neetu

2016-05-01

Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation. Hcy intracerebral (IC) treatment significantly impaired cerebral blood flow (CBF), and cerebral circulation and memory function. Hcy treatment also decreases the expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) in the brain along with increased expression of NMDA-R (NR1) and synaptosomal Ca(2+) indicating excitotoxicity. Additionally, we found that Hcy treatment increased protein and mRNA expression of intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 and also increased MMP-2 and MMP-9 activity in the brain. The increased expression of ICAM-1, glial fibrillary acidic protein (GFAP), and the decreased expression of vascular endothelial (VE)-cadherin and claudin-5 indicates BBB disruption and vascular inflammation. Moreover, we also found decreased expression of microtubule-associated protein 2 (MAP-2), postsynaptic density protein 95 (PSD-95), synapse-associated protein 97 (SAP-97), synaptosomal-associated protein 25 (SNAP-25), synaptophysin, and brain-derived neurotrophic factor (BDNF) showing synapse dysfunction in the hippocampus. Furthermore, NaHS and MK801 treatment ameliorates BBB disruption, CBF, and synapse functions in the mice brain. These results demonstrate a neuro-protective effect of H2S over Hcy-induced

Surgery-induced hippocampal angiotensin II elevation causes blood-brain barrier disruption via MMP/TIMP in aged rats

Directory of Open Access Journals (Sweden)

Zhengqian eLi

2016-04-01

Full Text Available Reversible BBB disruption has been uniformly reported in several animal models of postoperative cognitive dysfunction (POCD. Nevertheless, the precise mechanism underlying this occurrence remains unclear. Using an aged rat model of POCD, we investigated the dynamic changes in expression of molecules involved in BBB disintegration, matrix metalloproteinase-2 (MMP-2 and -9 (MMP-9, as well as three of their endogenous tissue inhibitors (TIMP-1, -2, -3, and tried to establish the correlation between MMP/TIMP balance and surgery-induced hippocampal BBB disruption. We validated the increased hippocampal expression of angiotensin II (Ang II and Ang II receptor type 1 (AT1 after surgery. We also found MMP/TIMP imbalance as early as 6 h after surgery, together with increased BBB permeability and decreased expression of Occludin and zonula occludens-1 (ZO-1, as well as increased basal lamina protein laminin at 24 h postsurgery. The AT1 antagonist candesartan restored MMP/TIMP equilibrium and modulated expression of Occludin and laminin, but not ZO-1, thereby improving BBB permeability. These events were accompanied by suppression of the surgery-induced canonical nuclear factor-κB (NF-κB activation cascade. Nevertheless, AT1 antagonism did not affect nuclear receptor peroxisome proliferator-activated receptor-γ expression. Collectively, these findings suggest that surgery-induced Ang II release impairs BBB integrity by activating NF-κB signaling and disrupting downstream MMP/TIMP balance via AT1 receptor.

Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

International Nuclear Information System (INIS)

Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

2011-01-01

Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

Il camouflage nel campo allargato. Variazioni su Disruptive Pattern Material e Dazzle Painting nella cultura visiva contemporanea

OpenAIRE

Maite Méndez Baiges

2016-01-01

The First World War was the scenario that led to the invention and systematic use of military camouflage techniques. Between them, the two fundamental modes of static or pictorial camouflage: mimetic, known as Disruptive Pattern Material, and the naval, called Dazzle Painting. Avantgarde artists contributed to their birth. Immediately, there was the transfer of these techniques to the civilian sphere, revealing that its essentially practical essence did not prevent the exploitation of its aes...

Metabolic disruption in context: Clinical avenues for synergistic perturbations in energy homeostasis by endocrine disrupting chemicals.

Science.gov (United States)

Sargis, Robert M

2015-01-01

The global epidemic of metabolic disease is a clear and present danger to both individual and societal health. Understanding the myriad factors contributing to obesity and diabetes is essential for curbing their decades-long expansion. Emerging data implicate environmental endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases such as obesity and diabetes. The phenylsulfamide fungicide and anti-fouling agent tolylfluanid (TF) was recently added to the list of EDCs promoting metabolic dysfunction. Dietary exposure to this novel metabolic disruptor promoted weight gain, increased adiposity, and glucose intolerance as well as systemic and cellular insulin resistance. Interestingly, the increase in body weight and adipose mass was not a consequence of increased food consumption; rather, it may have resulted from disruptions in diurnal patterns of energy intake, raising the possibility that EDCs may promote metabolic dysfunction through alterations in circadian rhythms. While these studies provide further evidence that EDCs may promote the development of obesity and diabetes, many questions remain regarding the clinical factors that modulate patient-specific consequences of EDC exposure, including the impact of genetics, diet, lifestyle, underlying disease, pharmacological treatments, and clinical states of fat redistribution. Currently, little is known regarding the impact of these factors on an individual's susceptibility to environmentally-mediated metabolic disruption. Advances in these areas will be critical for translating EDC science into the clinic to enable physicians to stratify an individual's risk of developing EDC-induced metabolic disease and to provide direction for treating exposed patients.

Cue-induced alcohol-seeking behaviour is reduced by disrupting the reconsolidation of alcohol-related memories.

Science.gov (United States)

von der Goltz, Christoph; Vengeliene, Valentina; Bilbao, Ainhoa; Perreau-Lenz, Stephanie; Pawlak, Cornelius R; Kiefer, Falk; Spanagel, Rainer

2009-08-01

In humans, the retrieval of memories associated with an alcohol-related experience frequently evokes alcohol-seeking behaviour. The reconsolidation hypothesis states that a consolidated memory could again become labile and susceptible to disruption after memory retrieval. The aim of our study was to examine whether retrieval of alcohol-related memories undergoes a reconsolidation process. For this purpose, male Wistar rats were trained to self-administer ethanol in the presence of specific conditioned stimuli. Thereafter, animals were left undisturbed in their home cages for the following 21 days. Memory retrieval was performed in a single 5-min exposure to all alcohol-associated stimuli. The protein synthesis inhibitor anisomycin, the non-competitive N-methyl-D: -aspartate (NMDA) receptor antagonist MK-801 and acamprosate, a clinically used drug known to reduce a hyper-glutamatergic state, were given immediately after retrieval of alcohol-related memories. The impact of drug treatment on cue-induced alcohol-seeking behaviour was measured on the following day and 7 days later. Administration of both anisomycin and MK-801 reduced cue-induced alcohol-seeking behaviour, showing that memory reconsolidation was disrupted by these compounds. However, acamprosate had no effect on the reconsolidation process, suggesting that this process is not dependent on a hyper-glutamatergic state but is more related to protein synthesis and NMDA receptor activity. Pharmacological disruption of reconsolidation of alcohol-associated memories can be achieved by the use of NMDA antagonists and protein synthesis inhibitors and may thus provide a potential new therapeutic strategy for the prevention of relapse in alcohol addiction.

Survey of disruption causes at JET

International Nuclear Information System (INIS)

De Vries, P.C.; Johnson, M.F.; Alper, B.; Hender, T.C.; Riccardo, V.; Buratti, P.; Koslowski, H.R.

2011-01-01

A survey has been carried out into the causes of all 2309 disruptions over the last decade of JET operations. The aim of this survey was to obtain a complete picture of all possible disruption causes, in order to devise better strategies to prevent or mitigate their impact. The analysis allows the effort to avoid or prevent JET disruptions to be more efficient and effective. As expected, a highly complex pattern of chain of events that led to disruptions emerged. It was found that the majority of disruptions had a technical root cause, for example due to control errors, or operator mistakes. These bring a random, non-physics, factor into the occurrence of disruptions and the disruption rate or disruptivity of a scenario may depend more on technical performance than on physics stability issues. The main root cause of JET disruptions was nevertheless due to neo-classical tearing modes that locked, closely followed in second place by disruptions due to human error. The development of more robust operational scenarios has reduced the JET disruption rate over the last decade from about 15% to below 4%. A fraction of all disruptions was caused by very fast, precursorless unpredictable events. The occurrence of these disruptions may set a lower limit of 0.4% to the disruption rate of JET. If one considers on top of that human error and all unforeseen failures of heating or control systems this lower limit may rise to 1.0% or 1.6%, respectively.

Alteration of sheep coat color pattern by disruption of ASIP gene via CRISPR Cas9.

Science.gov (United States)

Zhang, Xuemei; Li, Wenrong; Liu, Chenxi; Peng, Xinrong; Lin, Jiapeng; He, Sangang; Li, Xuejiao; Han, Bing; Zhang, Ning; Wu, Yangsheng; Chen, Lei; Wang, Liqin; MaYila; Huang, Juncheng; Liu, Mingjun

2017-08-15

Coat color is an important characteristic and economic trait in domestic sheep. Aiming at alteration of Chinese merino sheep coat color by genome manipulation, we disrupted sheep agouti signaling protein gene by CRISPR/Cas9. A total of seven indels were identified in 5 of 6 born lambs. Each targeted lamb happened at least two kinds of modifications, and targeted lambs with multiple modifications displayed variety of coat color patterns. Three lambs with 4 bp deletion showed badgerface with black body coat color in two lambs, and brown coat color with light ventral pigmentation in another one. The black-white spotted color was observed in two lambs with 2 bp deletion. Further analysis unraveled that modifications happened in one or more than two copies of ASIP gene, and moreover, the additional spontaneous mutations of D 9 and/or D 5 preceding the targeting modification could also involve the formation of coat color patterns. Taken together, the entanglement of ASIP modifications by CRISPR/Cas9, spontaneous D 9 /D 5 mutations, and ASIP gene duplications contributed to the variety of coat color patterns in targeted lambs.

Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption.

Science.gov (United States)

Moosavi, Maryam; Zarifkar, Amir Hossein; Farbood, Yaghoub; Dianat, Mahin; Sarkaki, Alireza; Ghasemi, Rasoul

2014-08-05

Centrally administered streptozotocin (STZ), is known to cause Alzheimer׳s like memory deterioration. It mainly affects insulin signaling pathways such as PI3/Akt and GSK-3β which are involved in cell survival. Previous studies indicate that STZ increases the ratio of Bax/Bcl-2 and thereby induces caspase-3 activation and apoptosis. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study aimed to assess if agmatine reverses STZ-induced memory deficits, hippocampal Akt/GSK-3β signaling disruption and caspase-3 activation. Adult male Sprague-Dawely rats weighing 200-250 g were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg) and agmatine treatment (40 or 80 mg/kg) was started from day 4 and continued in an every other day manner till day 14. The animal׳s learning and memory capability was assessed on days 15-18 using Morris water maze. After complement of behavioral studies the hippocampi was isolated and the amounts of hippocampal cleaved caspase-3 (the landmark of apoptosis), Bax/Bcl-2 ratio, total and phosphorylated forms of GSK-3β and Akt were analyzed by western blot. The results showed that agmatine in 80 but not 40 mg/kg reversed the memory deterioration induced by STZ. Western blot analysis revealed that STZ prompted elevation of caspase-3; Bax/Bcl-2 ratio and disrupted Akt/GSK-3β signaling in the hippocampus. Agmatine treatment prevented apoptosis and Akt/GSK-3β signaling impairment induced by STZ. This study disclosed that agmatine treatment averts not only STZ-induced memory deterioration but also hippocampal apoptosis and Akt/GSK-3β signaling disruption. Copyright © 2014 Elsevier B.V. All rights reserved.

Distal-less induces elemental color patterns in Junonia butterfly wings.

Science.gov (United States)

Dhungel, Bidur; Ohno, Yoshikazu; Matayoshi, Rie; Iwasaki, Mayo; Taira, Wataru; Adhikari, Kiran; Gurung, Raj; Otaki, Joji M

2016-01-01

The border ocellus, or eyespot, is a conspicuous color pattern element in butterfly wings. For two decades, it has been hypothesized that transcription factors such as Distal-less (Dll) are responsible for eyespot pattern development in butterfly wings, based on their expression in the prospective eyespots. In particular, it has been suggested that Dll is a determinant for eyespot size. However, functional evidence for this hypothesis has remained incomplete, due to technical difficulties. Here, we show that ectopically expressed Dll induces ectopic elemental color patterns in the adult wings of the blue pansy butterfly, Junonia orithya (Lepidoptera, Nymphalidae). Using baculovirus-mediated gene transfer, we misexpressed Dll protein fused with green fluorescent protein (GFP) in pupal wings, resulting in ectopic color patterns, but not the formation of intact eyespots. Induced changes included clusters of black and orange scales (a basic feature of eyespot patterns), black and gray scales, and inhibition of cover scale development. In contrast, ectopic expression of GFP alone did not induce any color pattern changes using the same baculovirus-mediated gene transfer system. These results suggest that Dll plays an instructive role in the development of color pattern elements in butterfly wings, although Dll alone may not be sufficient to induce a complete eyespot. This study thus experimentally supports the hypothesis of Dll function in eyespot development.

Fuel retention and recovery in natural and MGI disruptions on KSTAR

International Nuclear Information System (INIS)

Yu, Y.W.; Hong, S.H.; Yoon, S.W.; Kim, K.P.; Kim, W.C.; Seo, D.C.

2013-01-01

Fuel retention and recovery are studied during natural and Massive Gas Injection (MGI) induced disruptions in KSTAR with full graphite wall. The amount of released particles in natural disruptions in 15 s after the discharge is ∼5–10 times higher than that of non-disruption shots, but the difference is only ∼ 2 MGI induced disruptions depends on magnetic field (B t ) and MGI amount. The MGI disruption under a low B t and a medium MGI amount shows shorter thermal quench (TQ) and current quench (CQ), thereby higher fuel recovery. High B t plasma requires higher MGI amount for both disruption mitigation and fuel recovery. A high recovery of 4.2 × 10 22 D (∼0.78 monolayers) is obtained by MGI disruption in KSTAR 2011

Disruption of the thyroid system by the thyroid-disrupting compound Aroclor 1254 in juvenile Japanese flounder (Paralichthys olivaceus.

Directory of Open Access Journals (Sweden)

Yifei Dong

Full Text Available Polychlorinated biphenyls (PCBs are a group of persistent organochlorine compounds that have the potential to disrupt the homeostasis of thyroid hormones (THs in fish, particularly juveniles. In this study, thyroid histology, plasma TH levels, and iodothyronine deiodinase (IDs, including ID1, ID2, and ID3 gene expression patterns were examined in juvenile Japanese flounder (Paralichthys olivaceus following 25- and 50-day waterborne exposure to environmentally relevant concentrations of a commercial PCB mixture, Aroclor 1254 (10, 100, and 1000 ng/L with two-thirds of the test solutions renewed daily. The results showed that exposure to Aroclor 1254 for 50 d increased follicular cell height, colloid depletion, and hyperplasia. In particular, hypothyroidism, which was induced by the administration of 1000 ng/L Aroclor 1254, significantly decreased plasma TT4, TT3, and FT3 levels. Profiles of the changes in mRNA expression levels of IDs were observed in the liver and kidney after 25 and 50 d PCB exposure, which might be associated with a reduction in plasma THs levels. The expression level of ID2 mRNA in the liver exhibited a dose-dependent increase, indicating that this ID isotype might serve as sensitive and stable indicator for thyroid-disrupting chemical (TDC exposure. Overall, our study confirmed that environmentally relevant concentrations of Aroclor 1254 cause significant thyroid disruption, with juvenile Japanese flounder being suitable candidates for use in TDC studies.

Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Herbert, Katharine J. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Holloway, Adele [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Cook, Anthony L. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Chin, Suyin P. [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia)

2014-11-15

Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

International Nuclear Information System (INIS)

Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

2014-01-01

Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals

Science.gov (United States)

Zeng, Ying; Yang, Kai; Tong, Li; Yan, Bin

2018-01-01

Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods. PMID:29534515

Investigating Patterns for Self-Induced Emotion Recognition from EEG Signals.

Science.gov (United States)

Zhuang, Ning; Zeng, Ying; Yang, Kai; Zhang, Chi; Tong, Li; Yan, Bin

2018-03-12

Most current approaches to emotion recognition are based on neural signals elicited by affective materials such as images, sounds and videos. However, the application of neural patterns in the recognition of self-induced emotions remains uninvestigated. In this study we inferred the patterns and neural signatures of self-induced emotions from electroencephalogram (EEG) signals. The EEG signals of 30 participants were recorded while they watched 18 Chinese movie clips which were intended to elicit six discrete emotions, including joy, neutrality, sadness, disgust, anger and fear. After watching each movie clip the participants were asked to self-induce emotions by recalling a specific scene from each movie. We analyzed the important features, electrode distribution and average neural patterns of different self-induced emotions. Results demonstrated that features related to high-frequency rhythm of EEG signals from electrodes distributed in the bilateral temporal, prefrontal and occipital lobes have outstanding performance in the discrimination of emotions. Moreover, the six discrete categories of self-induced emotion exhibit specific neural patterns and brain topography distributions. We achieved an average accuracy of 87.36% in the discrimination of positive from negative self-induced emotions and 54.52% in the classification of emotions into six discrete categories. Our research will help promote the development of comprehensive endogenous emotion recognition methods.

Disruption of crystalline structure of Sn3.5Ag induced by electric current

International Nuclear Information System (INIS)

Huang, Han-Chie; Lin, Kwang-Lung; Wu, Albert T.

2016-01-01

This study presented the disruption of the Sn and Ag_3Sn lattice structures of Sn3.5Ag solder induced by electric current at 5–7 × 10"3 A/cm"2 with a high resolution transmission electron microscope investigation and electron diffraction analysis. The electric current stressing induced a high degree of strain on the alloy, as estimated from the X-ray diffraction (XRD) peak shift of the current stressed specimen. The XRD peak intensity of the Sn matrix and the Ag_3Sn intermetallic compound diminished to nearly undetectable after 2 h of current stressing. The electric current stressing gave rise to a high dislocation density of up to 10"1"7/m"2. The grain morphology of the Sn matrix became invisible after prolonged current stressing as a result of the coalescence of dislocations.

Ketamine alleviates bradykinin-induced disruption of the mouse cerebrovascular endothelial cell-constructed tight junction barrier via a calcium-mediated redistribution of occludin polymerization

International Nuclear Information System (INIS)

Chen, Jui-Tai; Lin, Yi-Ling; Chen, Ta-Liang; Tai, Yu-Ting; Chen, Cheng-Yu; Chen, Ruei-Ming

2016-01-01

Highlights: • Ketamine could suppress bradykinin-induced intracellular calcium mobilization. • Ketamine induced B1R protein and mRNA expressions but did not change B2R protein levels. • Ketamine attenuated bradykinin-induced redistribution of occludin tight junctions. • Ketamine prevented bradykinin-induced breakage of the MCEC-constructed tight junction barrier. - Abstract: Following brain injury, a sequence of mechanisms leads to disruption of the blood-brain barrier (BBB) and subsequent cerebral edema, which is thought to begin with activation of bradykinin. Our previous studies showed that ketamine, a widely used intravenous anesthetic agent, can suppress bradykinin-induced cell dysfunction. This study further aimed to evaluate the protective effects of ketamine against bradykinin-induced disruption of the mouse cerebrovascular endothelial cell (MCEC)-constructed tight junction barrier and the possible mechanisms. Exposure of MCECs to bradykinin increased intracellular calcium (Ca 2+ ) concentrations in a time-dependent manner. However, pretreatment of MCECs with ketamine time- and concentration-dependently lowered the bradykinin-induced calcium influx. As to the mechanisms, although exposure of MCECs to ketamine induced bradykinin R1 receptor protein and mRNA expression, this anesthetic did not change levels of the bradykinin R2 receptor, a major receptor that responds to bradykinin stimulation. Bradykinin increased amounts of soluble occludin in MCECs, but pretreatment with ketamine alleviated this disturbance in occludin polymerization. Consequently, exposure to bradykinin decreased the transendothelial electronic resistance in the MCEC-constructed tight junction barrier. However, pretreatment with ketamine attenuated the bradykinin-induced disruption of the tight junction barrier. Taken together, this study shows that ketamine at a therapeutic concentration can protect against bradykinin-induced breakage of the BBB via suppressing calcium

Comparison between 3D eddy current patterns in tokamak in-vessel components generated by disruptions

International Nuclear Information System (INIS)

Sakellaris, J.; Crutzen, Y.

1996-01-01

During plasma disruption events in Tokamaks, a large amount of magnetic energy is associated to the transfer of plasma current into eddy currents in the passive structures. In the ITER program two design concepts have been proposed. One approach (ITER CDA design) is based on copper stabilization loops (i.e., twin loops) attached to box-shaped blanket segments, electrically and mechanically separated along the toroidal direction. For another design concept (ITER EDA design) based on lower plasma elongation there is no need for specific stabilization loops. The passive stabilization is obtained by toroidally continuous components (i.e., the plasma facing wall of the blanket segments allows a continuity along the toroidal direction). Consequently, toroidal currents flow, when electromagnetic transients occur. Electromagnetic loads appear in the blanket structures in case of plasma disruptions and/or vertical displacement events either for the ITER CDA design concept or for the ITER EDA design concept. In this paper the influence of the in-vessel design configuration concepts--insulated segments or electrically continuous structures--in terms of magnetic shielding and electric insulation on the magnitude and the flow pattern of the eddy currents is investigated. This investigation will allow a performance evaluation of the two proposed design concepts

Automatic location of disruption times in JET

Science.gov (United States)

Moreno, R.; Vega, J.; Murari, A.

2014-11-01

The loss of stability and confinement in tokamak plasmas can induce critical events known as disruptions. Disruptions produce strong electromagnetic forces and thermal loads which can damage fundamental components of the devices. Determining the disruption time is extremely important for various disruption studies: theoretical models, physics-driven models, or disruption predictors. In JET, during the experimental campaigns with the JET-C (Carbon Fiber Composite) wall, a common criterion to determine the disruption time consisted of locating the time of the thermal quench. However, with the metallic ITER-like wall (JET-ILW), this criterion is usually not valid. Several thermal quenches may occur previous to the current quench but the temperature recovers. Therefore, a new criterion has to be defined. A possibility is to use the start of the current quench as disruption time. This work describes the implementation of an automatic data processing method to estimate the disruption time according to this new definition. This automatic determination allows both reducing human efforts to locate the disruption times and standardizing the estimates (with the benefit of being less vulnerable to human errors).

Automatic location of disruption times in JET.

Science.gov (United States)

Moreno, R; Vega, J; Murari, A

2014-11-01

The loss of stability and confinement in tokamak plasmas can induce critical events known as disruptions. Disruptions produce strong electromagnetic forces and thermal loads which can damage fundamental components of the devices. Determining the disruption time is extremely important for various disruption studies: theoretical models, physics-driven models, or disruption predictors. In JET, during the experimental campaigns with the JET-C (Carbon Fiber Composite) wall, a common criterion to determine the disruption time consisted of locating the time of the thermal quench. However, with the metallic ITER-like wall (JET-ILW), this criterion is usually not valid. Several thermal quenches may occur previous to the current quench but the temperature recovers. Therefore, a new criterion has to be defined. A possibility is to use the start of the current quench as disruption time. This work describes the implementation of an automatic data processing method to estimate the disruption time according to this new definition. This automatic determination allows both reducing human efforts to locate the disruption times and standardizing the estimates (with the benefit of being less vulnerable to human errors).

Disruption of cortical integration during midazolam-induced light sedation.

Science.gov (United States)

Liang, Peipeng; Zhang, Han; Xu, Yachao; Jia, Wenbin; Zang, Yufeng; Li, Kuncheng

2015-11-01

This work examines the effect of midazolam-induced light sedation on intrinsic functional connectivity of human brain, using a randomized, double-blind, placebo-controlled, cross-over, within-subject design. Fourteen healthy young subjects were enrolled and midazolam (0.03 mg/kg of the participant's body mass, to a maximum of 2.5 mg) or saline were administrated with an interval of one week. Resting-state fMRI was conducted before and after administration for each subject. We focus on two types of networks: sensory related lower-level functional networks and higher-order functions related ones. Independent component analysis (ICA) was used to identify these resting-state functional networks. We hypothesize that the sensory (visual, auditory, and sensorimotor) related networks will be intact under midazolam-induced light sedation while the higher-order (default mode, executive control, salience networks, etc.) networks will be functionally disconnected. It was found that the functional integrity of the lower-level networks was maintained, while that of the higher-level networks was significantly disrupted by light sedation. The within-network connectivity of the two types of networks was differently affected in terms of direction and extent. These findings provide direct evidence that higher-order cognitive functions including memory, attention, executive function, and language were impaired prior to lower-level sensory responses during sedation. Our result also lends support to the information integration model of consciousness. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Hantavirus-induced disruption of the endothelial barrier: neutrophils are on the payroll.

Science.gov (United States)

Schönrich, Günther; Krüger, Detlev H; Raftery, Martin J

2015-01-01

Viral hemorrhagic fever caused by hantaviruses is an emerging infectious disease for which suitable treatments are not available. In order to improve this situation a better understanding of hantaviral pathogenesis is urgently required. Hantaviruses infect endothelial cell layers in vitro without causing any cytopathogenic effect and without increasing permeability. This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role. In this review we highlight the latest developments in hantavirus-induced immunopathogenesis. A possible contribution of neutrophils has been neglected so far. For this reason, we place special emphasis on the pathogenic role of neutrophils in disrupting the endothelial barrier.

Disruption of crystalline structure of Sn3.5Ag induced by electric current

Energy Technology Data Exchange (ETDEWEB)

Huang, Han-Chie; Lin, Kwang-Lung, E-mail: matkllin@mail.ncku.edu.tw [Department of Material Science and Engineering, National Cheng Kung University, Tainan 70101, Taiwan (China); Wu, Albert T. [Department of Chemical and Material Engineering, National Central University, Jhongli 32001, Taiwan (China)

2016-03-21

This study presented the disruption of the Sn and Ag{sub 3}Sn lattice structures of Sn3.5Ag solder induced by electric current at 5–7 × 10{sup 3} A/cm{sup 2} with a high resolution transmission electron microscope investigation and electron diffraction analysis. The electric current stressing induced a high degree of strain on the alloy, as estimated from the X-ray diffraction (XRD) peak shift of the current stressed specimen. The XRD peak intensity of the Sn matrix and the Ag{sub 3}Sn intermetallic compound diminished to nearly undetectable after 2 h of current stressing. The electric current stressing gave rise to a high dislocation density of up to 10{sup 17}/m{sup 2}. The grain morphology of the Sn matrix became invisible after prolonged current stressing as a result of the coalescence of dislocations.

Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B{sub 1}

Energy Technology Data Exchange (ETDEWEB)

Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S; Swanevelder, Sonja

2004-07-15

In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B{sub 1} (FB{sub 1}) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB{sub 1} containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB{sub 1} dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB{sub 1} treatment in the control rats was significantly (P<0.05) enhanced by the 2-AAF/PH cancer promotion treatment. The nodular and surrounding Sa levels returned to baseline following FB{sub 1} initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB{sub 1} treatment, the initiation effected by FB{sub 1} was less (P<0.01) sensitive to the accumulation of Sa in the nodular and surrounding tissues than DEN initiation and the 2-AAF/PH control treatment. In contrast, the So level of FB{sub 1} initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P<0.05) higher with the secondary FB{sub 1} treatment. Although, the FB{sub 1}-induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study.

Science.gov (United States)

Lankelma, Jacqueline M; Cranendonk, Duncan R; Belzer, Clara; de Vos, Alex F; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

2017-09-01

The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens. As such, the use of antibiotics may attribute to immunosuppression as seen in sepsis. We aimed to test whether disruption of the gut microbiota affects systemic innate immune responses during endotoxemia in healthy subjects. In this proof-of-principle intervention trial, 16 healthy young men received either no treatment or broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days, after which all were administered lipopolysaccharide intravenously to induce a transient sepsis-like syndrome. At various time points, blood and faeces were sampled. Gut microbiota diversity was significantly lowered by the antibiotic treatment in all subjects. Clinical parameters, neutrophil influx, cytokine production, coagulation activation and endothelial activation during endotoxemia were not different between antibiotic-pretreated and control individuals. Antibiotic treatment had no impact on blood leucocyte responsiveness to various Toll-like receptor ligands and clinically relevant causative agents of sepsis ( Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli ) during endotoxemia. These findings suggest that gut microbiota disruption by broad-spectrum antibiotics does not affect systemic innate immune responses in healthy subjects during endotoxemia in humans, disproving our hypothesis. Further research is needed to test this hypothesis in critically ill patients. These data underline the importance of translating findings in mice to humans. ClinicalTrials.gov (NCT02127749; Pre-results). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

Parietal disruption alters audiovisual binding in the sound-induced flash illusion.

Science.gov (United States)

Kamke, Marc R; Vieth, Harrison E; Cottrell, David; Mattingley, Jason B

2012-09-01

Selective attention and multisensory integration are fundamental to perception, but little is known about whether, or under what circumstances, these processes interact to shape conscious awareness. Here, we used transcranial magnetic stimulation (TMS) to investigate the causal role of attention-related brain networks in multisensory integration between visual and auditory stimuli in the sound-induced flash illusion. The flash illusion is a widely studied multisensory phenomenon in which a single flash of light is falsely perceived as multiple flashes in the presence of irrelevant sounds. We investigated the hypothesis that extrastriate regions involved in selective attention, specifically within the right parietal cortex, exert an influence on the multisensory integrative processes that cause the flash illusion. We found that disruption of the right angular gyrus, but not of the adjacent supramarginal gyrus or of a sensory control site, enhanced participants' veridical perception of the multisensory events, thereby reducing their susceptibility to the illusion. Our findings suggest that the same parietal networks that normally act to enhance perception of attended events also play a role in the binding of auditory and visual stimuli in the sound-induced flash illusion. Copyright © 2012 Elsevier Inc. All rights reserved.

Stent-assisted, balloon-induced intimal disruption and relamination of aortic dissection in patients with Marfan syndrome: Midterm outcomes and aortic remodeling.

Science.gov (United States)

Faure, Elsa Madeleine; El Batti, Salma; Abou Rjeili, Marwan; Ben Abdallah, Iannis; Julia, Pierre; Alsac, Jean-Marc

2018-05-17

The study objective was to assess the midterm outcomes and aortic remodeling in patients with Marfan syndrome with complicated acute type B aortic dissection treated with stent-assisted, balloon-induced intimal disruption and relamination. We reviewed all patients treated with stent-assisted, balloon-induced intimal disruption and relamination for a complicated acute type B aortic dissection associated with Marfan syndrome according to the revised Ghent criteria. Between 2015 and November 2017, 7 patients with Marfan syndrome underwent stent-assisted, balloon-induced intimal disruption and relamination for a complicated acute type B aortic dissection. The median age of patients was 47 years (range, 23-70). Four patients had a history of aortic root replacement. Technical success was achieved in 100%. Three patients required an adjunctive procedure for renal artery stenting (n = 2) and iliac artery stenting (n = 1). There was no in-hospital death, 30-day postoperative stroke, spinal cord ischemia, ischemic colitis, or renal failure requiring dialysis. At a median follow-up of 15 months (range, 7-28), 1 patient required aortic arch replacement for aneurysmal degeneration associated with a type Ia endoleak at 2 years, giving a late reintervention rate of 14%. There was no other secondary endoleak. The primary visceral patency rate was 100%. There were no all-cause deaths reported. At last computed tomography scan, all patients had complete aortic remodeling of the treated thoracoabdominal aorta. Distally, at the nonstented infrarenal aortoiliac level, 6 patients had persistent false lumen flow with stable aorto-iliac diameter in 5. One patient had iliac diameter growth (27 mm diameter at last computed tomography scan). Stent-assisted, balloon-induced intimal disruption and relamination of aortic dissection in patients with Marfan syndrome is feasible, safe, and associated with an immediate and midterm persisting thoracoabdominal aortic remodeling. Copyright �

Carbendazim has the potential to induce oxidative stress, apoptosis, immunotoxicity and endocrine disruption during zebrafish larvae development.

Science.gov (United States)

Jiang, Jinhua; Wu, Shenggan; Wang, Yanhua; An, Xuehua; Cai, Leiming; Zhao, Xueping; Wu, Changxing

2015-10-01

Increasing evidence have suggested deleterious effects of carbendazim on reproduction, apoptosis, immunotoxicity and endocrine disruption in mice and rats, however, the developmental toxicity of carbendazim to aquatic organisms remains obscure. In the present study, we utilized zebrafish as an environmental monitoring model to characterize the effects of carbendazim on expression of genes related to oxidative stress, apoptosis, immunotoxicity and endocrine disruption during larval development. Different trends in gene expression were observed upon exposing the larvae to 4, 20, 100, and 500 μg/L carbendazim for 4 and 8d. The mRNA levels of catalase, glutathione peroxidase and manganese superoxide dismutase (CAT, GPX, and Mn/SOD) were up-regulated after exposure to different concentrations of carbendazim for 4 or 8d. The up-regulation of p53, Apaf1, Cas8 and the down-regulation of Bcl2, Mdm2, Cas3 in the apoptosis pathway, as well as the increased expression of cytokines and chemokines, including CXCL-C1C, CCL1, IL-1b, IFN, IL-8, and TNFα, suggested carbendazim might trigger apoptosis and immune response during zebrafish larval development. In addition, the alteration of mRNA expression of VTG, ERα, ERβ1, ERβ2, TRα, TRβ, Dio1, and Dio2 indicated the potential of carbendazim to induce endocrine disruption in zebrafish larvae. These data suggested that carbendazim could simultaneously induce multiple responses during zebrafish larval development, and bidirectional interactions among oxidative stress, apoptosis pathway, immune and endocrine systems might be present. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enzymatic cell disruption of microalgae biomass in biorefinery processes.

Science.gov (United States)

Demuez, Marie; Mahdy, Ahmed; Tomás-Pejó, Elia; González-Fernández, Cristina; Ballesteros, Mercedes

2015-10-01

When employing biotechnological processes for the procurement of biofuels and bio-products from microalgae, one of the most critical steps affecting economy and yields is the "cell disruption" stage. Currently, enzymatic cell disruption has delivered effective and cost competitive results when compared to mechanical and chemical cell disruption methods. However, the introduction of enzymes implies additional associated cost within the overall process. In order to reduce this cost, autolysis of microalgae is proposed as alternative enzymatic cell disruption method. This review aims to provide the state of the art of enzymatic cell disruption treatments employed in biorefinery processes and highlights the use of endopeptidases. During the enzymatic processes of microalgae life cycle, some lytic enzymes involved in cell division and programmed cell death have been proven useful in performing cell lysis. In this context, the role of endopeptidases is emphasized. Mirroring these natural events, an alternative cell disruption approach is proposed and described with the potential to induce the autolysis process using intrinsic cell enzymes. Integrating induced autolysis within biofuel production processes offers a promising approach to reduce overall global costs and energetic input associated with those of current cell disruption methods. A number of options for further inquiry are also discussed. © 2015 Wiley Periodicals, Inc.

Acute neuroinflammation impairs context discrimination memory and disrupts pattern separation processes in hippocampus.

Science.gov (United States)

Czerniawski, Jennifer; Guzowski, John F

2014-09-10

Although it is known that immune system activation can impair cognition, no study to date has linked cognitive deficits during acute neuroinflammation to dysregulation of task-relevant neuronal ensemble activity. Here, we assessed both neural circuit activity and context discrimination memory retrieval, in a within-subjects design, of male rats given systemic administration of saline or lipopolysaccharide (LPS). Rats were exposed over several days to two similar contexts: one of which was paired with weak foot shock and the other was not. After reaching criteria for discriminative freezing, rats were given systemic LPS or saline injection and tested for retrieval of context discrimination 6 h later. Importantly, LPS administration produced an acute neuroinflammatory response in dorsal hippocampus at this time (as assessed by elevation of proinflammatory cytokine mRNA levels) and abolished retrieval of the previously acquired discrimination. The impact of neuroinflammation on hippocampal CA3 and CA1 neural circuit activity was assessed using the Arc/Homer1a cellular analysis of temporal activity by fluorescence in situ hybridization imaging method. Whereas the saline-treated subjects discriminated and had low overlap of hippocampal ensembles activated in the two contexts, LPS-treated subjects did not discriminate and had greater ensemble overlap (i.e., reduced orthogonalization). Additionally, retrieval of standard contextual fear conditioning, which does not require context discrimination, was not affected by pretesting LPS administration. Together, the behavioral and circuit analyses data provide compelling evidence that LPS administration impairs context discrimination memory by disrupting cellular pattern separation processes within the hippocampus, thus linking acute neuroinflammation to disruption of specific neural circuit functions and cognitive impairment. Copyright © 2014 the authors 0270-6474/14/3412470-11$15.00/0.

Haemorrhagic snake venom metalloproteases and human ADAMs cleave LRP5/6, which disrupts cell-cell adhesions in vitro and induces haemorrhage in vivo.

Science.gov (United States)

Seo, Tadahiko; Sakon, Taketo; Nakazawa, Shiori; Nishioka, Asuka; Watanabe, Kohei; Matsumoto, Kaori; Akasaka, Mari; Shioi, Narumi; Sawada, Hitoshi; Araki, Satohiko

2017-06-01

Snake venom metalloproteases (SVMPs) are members of the a disintegrin and metalloprotease (ADAM) family of proteins, as they possess similar domains. SVMPs are known to elicit snake venom-induced haemorrhage; however, the target proteins and cleavage sites are not known. In this work, we identified a target protein of vascular apoptosis-inducing protein 1 (VAP1), an SVMP, relevant to its ability to induce haemorrhage. VAP1 disrupted cell-cell adhesions by relocating VE-cadherin and γ-catenin from the cell-cell junction to the cytosol, without inducing proteolysis of VE-cadherin. The Wnt receptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are known to promote catenin relocation, and are rendered constitutively active in Wnt signalling by truncation. Thus, we examined whether VAP1 cleaves LRP5/6 to induce catenin relocation. Indeed, we found that VAP1 cleaved the extracellular region of LRP6 and LRP5. This cleavage removes four inhibitory β-propeller structures, resulting in activation of LRP5/6. Recombinant human ADAM8 and ADAM12 also cleaved LRP6 at the same site. An antibody against a peptide including the LRP6-cleavage site inhibited VAP1-induced VE-cadherin relocation and disruption of cell-cell adhesions in cultured cells, and blocked haemorrhage in mice in vivo. Intriguingly, animals resistant to the effects of haemorrhagic snake venom express variants of LRP5/6 that lack the VAP1-cleavage site, or low-density lipoprotein receptor domain class A domains involved in formation of the constitutively active form. The results validate LRP5/6 as physiological targets of ADAMs. Furthermore, they indicate that SVMP-induced cleavage of LRP5/6 causes disruption of cell-cell adhesion and haemorrhage, potentially opening new avenues for the treatment of snake bites. © 2017 Federation of European Biochemical Societies.

Non-disruptive regime changes-The case of competing energy efficient lighting trajectories

DEFF Research Database (Denmark)

Franceschini, Simone; Alkemade, Floortje

2016-01-01

Technologies within the same industry are expected to follow similar patterns of innovation, and when the dominant patterns change, this is often expected to have disruptive effects on the industry. However, the three most recent lighting technologies (fluorescent, compact fluorescent, and LED......) show different patterns of innovative activities despite similarities in the determinants of innovation; and we observed multiple technological regimes within the lighting industry. Furthermore, we observed changes in these innovative patterns without widespread disruptive effects. While FL and LED...... for policymakers in stimulating new technologies in industries with undesirable Mark II pattern through the influence of all the dimensions of the technological regimes....

Hantavirus-induced disruption of the endothelial barrier: Neutrophils are on the payroll

Directory of Open Access Journals (Sweden)

Günther eSchönrich

2015-03-01

Full Text Available Viral hemorrhagic fever caused by hantaviruses is an emerging infectious disease for which suita-ble treatments are not available. In order to improve this situation a better understanding of han-taviral pathogenesis is urgently required. Hantaviruses infect endothelial cell layers in vitro with-out causing any cytopathogenic effect and without increasing permeability. This implies that the mechanisms underlying vascular hyperpermeability in hantavirus-associated disease are more complex and that immune mechanisms play an important role. In this review we highlight the lat-est developments in hantavirus-induced immunopathogenesis. A possible contribution of neutro-phils has been neglected so far. For this reason, we place special emphasis on the pathogenic role of neutrophils in disrupting the endothelial barrier.

Plasma disruption modeling and simulation

International Nuclear Information System (INIS)

Hassanein, A.

1994-01-01

Disruptions in tokamak reactors are considered a limiting factor to successful operation and reliable design. The behavior of plasma-facing components during a disruption is critical to the overall integrity of the reactor. Erosion of plasma facing-material (PFM) surfaces due to thermal energy dump during the disruption can severely limit the lifetime of these components and thus diminish the economic feasibility of the reactor. A comprehensive understanding of the interplay of various physical processes during a disruption is essential for determining component lifetime and potentially improving the performance of such components. There are three principal stages in modeling the behavior of PFM during a disruption. Initially, the incident plasma particles will deposit their energy directly on the PFM surface, heating it to a very high temperature where ablation occurs. Models for plasma-material interactions have been developed and used to predict material thermal evolution during the disruption. Within a few microseconds after the start of the disruption, enough material is vaporized to intercept most of the incoming plasma particles. Models for plasma-vapor interactions are necessary to predict vapor cloud expansion and hydrodynamics. Continuous heating of the vapor cloud above the material surface by the incident plasma particles will excite, ionize, and cause vapor atoms to emit thermal radiation. Accurate models for radiation transport in the vapor are essential for calculating the net radiated flux to the material surface which determines the final erosion thickness and consequently component lifetime. A comprehensive model that takes into account various stages of plasma-material interaction has been developed and used to predict erosion rates during reactor disruption, as well during induced disruption in laboratory experiments

Magnetoresistance and ion bombardment induced magnetic patterning

International Nuclear Information System (INIS)

Hoeink, V.

2008-01-01

In this thesis the combination of the magnetic patterning of the unidirectional anisotropy and the tunnel magnetoresistance effect is investigated. In my diploma thesis, it has been shown that it is in principle possible to use the magnetic patterning by ion bombardment to magnetically structure the pinned layer in magnetic tunnel junctions (MTJs) with alumina barrier. Furthermore, it has been shown that the side effects which have been observed after this treatment can be at least reduced by an additional heating step. Starting from this point, the applicability of ion bombardment induced magnetic patterning (IBMP) in general and the combination of IBMP and MTJs in particular is investigated and new applications are developed. (orig.)

Endocrine Disrupting Chemical Induced "Pollution of Metabolic Pathways": A Case of Shifting Paradigms With Implications for Vascular Diseases.

Science.gov (United States)

Janardhanan, Rajiv

2018-05-14

The latter half of the twentieth century has witnessed a humongous spurt in the use of synthetic chemicals in a wide variety of industrial and agricultural applications are leading to niche specific perturbations affecting every trophic level of the ecosystems due to unmitigated environmental contamination. Despite the incremental usefulness of endocrine disrupting chemicals (EDCs) such as pesticides and plasticizers, their statutory impact on environmental health is assuming worrisome proportions. The EDCs can disrupt physiological homeostasis resulting in developmental and reproductive abnormalities. Both preclinical animal experiments, as well as epidemiological studies, have correlated EDC exposure with metabolic disorders such as metabolic syndrome, type 2 diabetes as well as cardiovascular health. Here we briefly review the statutory impact of EDCs on metabolic disruption as well as their impact on environmental health. Finally, difficulties pertaining to the categorization of EDC induced metabolic diseases as risk factors for global disease burden have been addressed taking into account the complexity of such interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Analytic modeling of axisymmetric disruption halo currents

International Nuclear Information System (INIS)

Humphreys, D.A.; Kellman, A.G.

1999-01-01

Currents which can flow in plasma facing components during disruptions pose a challenge to the design of next generation tokamaks. Induced toroidal eddy currents and both induced and conducted poloidal ''halo'' currents can produce design-limiting electromagnetic loads. While induction of toroidal and poloidal currents in passive structures is a well-understood phenomenon, the driving terms and scalings for poloidal currents flowing on open field lines during disruptions are less well established. A model of halo current evolution is presented in which the current is induced in the halo by decay of the plasma current and change in enclosed toroidal flux while being convected into the halo from the core by plasma motion. Fundamental physical processes and scalings are described in a simplified analytic version of the model. The peak axisymmetric halo current is found to depend on halo and core plasma characteristics during the current quench, including machine and plasma dimensions, resistivities, safety factor, and vertical stability growth rate. Two extreme regimes in poloidal halo current amplitude are identified depending on the minimum halo safety factor reached during the disruption. A 'type I' disruption is characterized by a minimum safety factor that remains relatively high (typically 2 - 3, comparable to the predisruption safety factor), and a relatively low poloidal halo current. A 'type II' disruption is characterized by a minimum safety factor comparable to unity and a relatively high poloidal halo current. Model predictions for these two regimes are found to agree well with halo current measurements from vertical displacement event disruptions in DIII-D [T. S. Taylor, K. H. Burrell, D. R. Baker, G. L. Jackson, R. J. La Haye, M. A. Mahdavi, R. Prater, T. C. Simonen, and A. D. Turnbull, open-quotes Results from the DIII-D Scientific Research Program,close quotes in Proceedings of the 17th IAEA Fusion Energy Conference, Yokohama, 1998, to be published in

Pentachlorophenol-Induced Cytotoxic, Mitogenic, and Endocrine-Disrupting Activities in Channel Catfish, Ictalurus punctatus

Directory of Open Access Journals (Sweden)

Paul B. Tchounwou

2004-09-01

Full Text Available Pentachlorophenol (PCP is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Although it has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action at the cellular and molecular levels. Recent investigations in our laboratory have shown that PCP induces cytotoxicity and transcriptionally activates stress genes in human liver carcinoma (HepG2 cells [1]. In this research, we hypothesize that environmental exposure to PCP may trigger cytotoxic, mitogenic, and endocrine-disrupting activities in aquatic organisms including fish. To test this hypothesis, we carried out in vitro cultures of male channel catfish hepatocytes, and performed the fluorescein diacetate assay (FDA to assess for cell viability, and the Western Blot analysis to assess for vitellogenin expression following exposure to PCP. Data obtained from FDA experiments indicated a strong dose-response relationship with respect to PCP cytotoxicity. Upon 48 hrs of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50 was computed to be 1,987.0 + 9.6 μg PCP/mL. The NOAEL and LOAEL were 62.5 + 10.3 μg PCP/mL and 125.0+15.2 μg PCP/mL, respectively. At lower levels of exposure, PCP was found to be mitogenic, showing a strong dose- and time-dependent response with regard to cell proliferation. Western Blot analysis demonstrated the potential of PCP to cause endocrine-disrupting activity, as evidenced by the up regulation of the 125-kDa vitellogenin protein the hepatocytes of male channel catfish.

Urbanization disrupts latitude-size rule in 17-year cicadas.

Science.gov (United States)

Beasley, DeAnna E; Penick, Clint A; Boateng, Nana S; Menninger, Holly L; Dunn, Robert R

2018-03-01

Many ectotherms show a decrease in body size with increasing latitude due to changes in climate, a pattern termed converse Bergmann's rule. Urban conditions-particularly warmer temperatures and fragmented landscapes-may impose stresses on development that could disrupt these body size patterns. To test the impact of urbanization on development and latitudinal trends in body size, we launched a citizen science project to collect periodical cicadas ( Magicicada septendecim ) from across their latitudinal range during the 2013 emergence of Brood II. Periodical cicadas are long-lived insects whose distribution spans a broad latitudinal range covering both urban and rural habitats. We used a geometric morphometric approach to assess body size and developmental stress based on fluctuating asymmetry in wing shape. Body size of rural cicadas followed converse Bergmann's rule, but this pattern was disrupted in urban habitats. In the north, urban cicadas were larger than their rural counterparts, while southern populations showed little variation in body size between habitats. We detected no evidence of differences in developmental stress due to urbanization. To our knowledge, this is the first evidence that urbanization disrupts biogeographical trends in body size, and this pattern highlights how the effects of urbanization may differ over a species' range.

Interactive effects of size, contrast, intensity and configuration of background objects in evoking disruptive camouflage in cuttlefish.

Science.gov (United States)

Chiao, Chuan-Chin; Chubb, Charles; Hanlon, Roger T

2007-07-01

Disruptive body coloration is a primary camouflage tactic of cuttlefish. Because rapid changeable coloration of cephalopods is guided visually, we can present different visual backgrounds (e.g., computer-generated, two-dimensional prints) and video record the animal's response by describing and grading its body pattern. We showed previously that strength of cuttlefish disruptive patterning depends on the size, contrast, and density of discrete light elements on a homogeneous dark background. Here we report five experiments on the interactions of these and other features. Results show that Weber contrast of light background elements is--in combination with element size--a powerful determinant of disruptive response strength. Furthermore, the strength of disruptive patterning decreases with increasing mean substrate intensity (with other factors held constant). Interestingly, when element size, Weber contrast and mean substrate intensity are kept constant, strength of disruptive patterning depends on the configuration of clusters of small light elements. This study highlights the interactions of multiple features of natural microhabitats that directly influence which camouflage pattern a cuttlefish will choose.

Evidence of an evolutionary hourglass pattern in herbivory-induced transcriptomic responses.

Science.gov (United States)

Durrant, Matthew; Boyer, Justin; Zhou, Wenwu; Baldwin, Ian T; Xu, Shuqing

2017-08-01

Herbivory-induced defenses are specific and activated in plants when elicitors, frequently found in the herbivores' oral secretions, are introduced into wounds during attack. While complex signaling cascades are known to be involved, it remains largely unclear how natural selection has shaped the evolution of these induced defenses. We analyzed herbivory-induced transcriptomic responses in wild tobacco, Nicotiana attenuata, using a phylotranscriptomic approach that measures the origin and sequence divergence of herbivory-induced genes. Highly conserved and evolutionarily ancient genes of primary metabolism were activated at intermediate time points (2-6 h) after elicitation, while less constrained and young genes associated with defense signaling and biosynthesis of specialized metabolites were activated at early (before 2 h) and late (after 6 h) stages of the induced response, respectively - a pattern resembling the evolutionary hourglass pattern observed during embryogenesis in animals and the developmental process in plants and fungi. The hourglass patterns found in herbivory-induced defense responses and developmental process are both likely to be a result of signaling modularization and differential evolutionary constraints on the modules involved in the signaling cascade. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Calculation of voltages and currents induced in the vacuum vessel of ASDEX by plasma disruptions

International Nuclear Information System (INIS)

Preis, H.

1978-01-01

An approximation method is used to analyze the electromagnetic diffusion process induced in the walls of the ASDEX vacuum vessel by plasma disruptions. For this purpose the rotational-symmetric vessel is regarded as N = 82 circular conductors connected in parallel and inductively coupled with one another and with the plasma. The transient currents and voltages occurring in this circuit are calculated with computer programs. From the calculated currents it is possible to determine the time behavior of the distributions of the current density and magnetic force density in the vessel walls. (orig.) [de

Time course of ongoing activity during neuritis and following axonal transport disruption.

Science.gov (United States)

Satkeviciute, Ieva; Goodwin, George; Bove, Geoffrey M; Dilley, Andrew

2018-05-01

Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.

Boundary-induced pattern formation from uniform temporal oscillation

Science.gov (United States)

Kohsokabe, Takahiro; Kaneko, Kunihiko

2018-04-01

Pattern dynamics triggered by fixing a boundary is investigated. By considering a reaction-diffusion equation that has a unique spatially uniform and limit cycle attractor under a periodic or Neumann boundary condition, and then by choosing a fixed boundary condition, we found three novel phases depending on the ratio of diffusion constants of activator to inhibitor: transformation of temporally periodic oscillation into a spatially periodic fixed pattern, travelling wave emitted from the boundary, and aperiodic spatiotemporal dynamics. The transformation into a fixed, periodic pattern is analyzed by crossing of local nullclines at each spatial point, shifted by diffusion terms, as is analyzed by using recursive equations, to obtain the spatial pattern as an attractor. The generality of the boundary-induced pattern formation as well as its relevance to biological morphogenesis is discussed.

Synergetic Effects of Runaway and Disruption Induced by VDE on the First Wall Damage in HL-2A

International Nuclear Information System (INIS)

Song Xianying; Yang Jinwei; Li Xu; Yuan Guoliang; Zhang Yipo

2012-01-01

The plasma facing component in HL-2A has been damaged seriously after disruption, and for this reason its operation is suspended for maintenance. The experimental phenomena and plasma configurations, calculated by the current filament code (CF-code) using the plasma parameters measured by diagnostics and the signals of the magnetic probes, confirm that the first wall is damaged by the synergetic effects of runaway electrons and disruption induced by a vertical displacement event (VDE). When the plasma column is displaced upward/downward, the strong runaway electrons normally hit the baffle plate of the MP 3 or MP 1 coil in the upper and lower divertor during the disruption, causing the baffle plates to be holed and wrinkled by the energetic runaway current, and water (for cooling or heating the baffle plates) to leak into the vacuum vessel. Another disastrous consequence is that bellows underlying the baffle plate and outside the coil of MP 3 for connecting two segments of the jacket casing pipe are punctured by arcing. The arc may be part of the halo current that forms a complete circuit. The experimental phenomena are indirect but compelling evidence for the existence of a halo current during the disruption and VDE, though the halo current has not been measured by the diagnostics in the HL-2A tokamak.

Synergetic Effects of Runaway and Disruption Induced by VDE on the First Wall Damage in HL-2A

Science.gov (United States)

Song, Xianying; Yang, Jinwei; Li, Xu; Yuan, Guoliang; Zhang, Yipo

2012-03-01

The plasma facing component in HL-2A has been damaged seriously after disruption, and for this reason its operation is suspended for maintenance. The experimental phenomena and plasma configurations, calculated by the current filament code (CF-code) using the plasma parameters measured by diagnostics and the signals of the magnetic probes, confirm that the first wall is damaged by the synergetic effects of runaway electrons and disruption induced by a vertical displacement event (VDE). When the plasma column is displaced upward/downward, the strong runaway electrons normally hit the baffle plate of the MP3 or MP1 coil in the upper and lower divertor during the disruption, causing the baffle plates to be holed and wrinkled by the energetic runaway current, and water (for cooling or heating the baffle plates) to leak into the vacuum vessel. Another disastrous consequence is that bellows underlying the baffle plate and outside the coil of MP3 for connecting two segments of the jacket casing pipe are punctured by arcing. The arc may be part of the halo current that forms a complete circuit. The experimental phenomena are indirect but compelling evidence for the existence of a halo current during the disruption and VDE, though the halo current has not been measured by the diagnostics in the HL-2A tokamak.

Perception of visual texture and the expression of disruptive camouflage by the cuttlefish, Sepia officinalis

Science.gov (United States)

Kelman, E.J; Baddeley, R.J; Shohet, A.J; Osorio, D

2007-01-01

Juvenile cuttlefish (Sepia officinalis) camouflage themselves by changing their body pattern according to the background. This behaviour can be used to investigate visual perception in these molluscs and may also give insight into camouflage design. Edge detection is an important aspect of vision, and here we compare the body patterns that cuttlefish produced in response to checkerboard backgrounds with responses to backgrounds that have the same spatial frequency power spectrum as the checkerboards, but randomized spatial phase. For humans, phase randomization removes visual edges. To describe the cuttlefish body patterns, we scored the level of expression of 20 separate pattern ‘components’, and then derived principal components (PCs) from these scores. After varimax rotation, the first component (PC1) corresponded closely to the so-called disruptive body pattern, and the second (PC2) to the mottle pattern. PC1 was predominantly expressed on checkerboards, and PC2 on phase-randomized backgrounds. Thus, cuttlefish probably have edge detectors that control the expression of disruptive pattern. Although the experiments used unnatural backgrounds, it seems probable that cuttlefish display disruptive camouflage when there are edges in the visual background caused by discrete objects such as pebbles. We discuss the implications of these findings for our understanding of disruptive camouflage. PMID:17389219

Patterns of experimentally induced pain in pericranial muscles

DEFF Research Database (Denmark)

Schmidt-Hansen, Peter Thede; Svensson, Peter; Jensen, Troels Staehelin

2006-01-01

into the masseter muscle (anova: P pain areas (anova: P cervically innervated muscles had significantly different patterns of spread and referral of pain according to trigeminally vs....... cervically innervated dermatomes (P pain patterns and pain sensitivity in different craniofacial muscles in healthy volunteers, which may be of importance for further research on different craniofacial pain conditions.......Nociceptive mechanisms in the craniofacial muscle tissue are poorly understood. The pain pattern in individual pericranial muscles has not been described before. Experimental muscle pain was induced by standardized infusions of 0.2 ml 1 m hypertonic saline into six craniofacial muscles (masseter...

Patterns induced by magnetic impurities in d-wave superconductors

International Nuclear Information System (INIS)

Zuo Xianjun; Gong Changde; Zhou Yuan

2010-01-01

We investigate the modulated patterns induced by magnetic impurities in d-wave superconductors (DSCs) near optimal doping based on the t-t ' -U-V model. Modulated checkerboard patterns with periodicity of eight or four lattice constants (8a or 4a) in the spin-, charge- and DSC orders are observed. Moreover, the checkerboard modulation in the spin order appear to be robust against parameter changes, which is consistent with neutron-scattering experiments. For the two-impurity case, a modulated stripe-like spin order with periodicity 8a is induced, which coexists with the DSC order. Further experiments of magnetic impurity substitution in DSCs are expected to check these results.

Patterns induced by magnetic impurities in d-wave superconductors

Science.gov (United States)

Zuo, Xian-Jun; Gong, Chang-De; Zhou, Yuan

2010-07-01

We investigate the modulated patterns induced by magnetic impurities in d-wave superconductors (DSCs) near optimal doping based on the t-t-U-V model. Modulated checkerboard patterns with periodicity of eight or four lattice constants (8 a or 4 a) in the spin-, charge- and DSC orders are observed. Moreover, the checkerboard modulation in the spin order appear to be robust against parameter changes, which is consistent with neutron-scattering experiments. For the two-impurity case, a modulated stripe-like spin order with periodicity 8 a is induced, which coexists with the DSC order. Further experiments of magnetic impurity substitution in DSCs are expected to check these results.

Runaway electron generation in tokamak disruptions

International Nuclear Information System (INIS)

Helander, P.; Andersson, F.; Fueloep, T.; Smith, H.; Anderson, D.; Lisak, M.; Eriksson, L.-G.

2005-01-01

The time evolution of the plasma current during a tokamak disruption is calculated by solving the equations for runaway electron production simultaneously with the induction equation for the toroidal electric field. The resistive diffusion time in a post-disruption plasma is typically comparable to the runaway avalanche growth time. Accordingly, the toroidal electric field induced after the thermal quench of a disruption diffuses radially through the plasma at the same time as it accelerates runaway electrons, which in turn back-react on the electric field. When these processes are accounted for in a self-consistent way, it is found that (1) the efficiency and time scale of runaway generation agrees with JET experiments; (2) the runaway current profile typically becomes more peaked than the pre-disruption current profile; and (3) can easily become radially filamented. It is also shown that higher runaway electron generation is expected if the thermal quench is sufficiently fast. (author)

The Non-structural Protein of Crimean-Congo Hemorrhagic Fever Virus Disrupts the Mitochondrial Membrane Potential and Induces Apoptosis*

Science.gov (United States)

Barnwal, Bhaskar; Karlberg, Helen; Mirazimi, Ali; Tan, Yee-Joo

2016-01-01

Viruses have developed distinct strategies to overcome the host defense system. Regulation of apoptosis in response to viral infection is important for virus survival and dissemination. Like other viruses, Crimean-Congo hemorrhagic fever virus (CCHFV) is known to regulate apoptosis. This study, for the first time, suggests that the non-structural protein NSs of CCHFV, a member of the genus Nairovirus, induces apoptosis. In this report, we demonstrated the expression of CCHFV NSs, which contains 150 amino acid residues, in CCHFV-infected cells. CCHFV NSs undergoes active degradation during infection. We further demonstrated that ectopic expression of CCHFV NSs induces apoptosis, as reflected by caspase-3/7 activity and cleaved poly(ADP-ribose) polymerase, in different cell lines that support CCHFV replication. Using specific inhibitors, we showed that CCHFV NSs induces apoptosis via both intrinsic and extrinsic pathways. The minimal active region of the CCHFV NSs protein was determined to be 93–140 amino acid residues. Using alanine scanning, we demonstrated that Leu-127 and Leu-135 are the key residues for NSs-induced apoptosis. Interestingly, CCHFV NSs co-localizes in mitochondria and also disrupts the mitochondrial membrane potential. We also demonstrated that Leu-127 and Leu-135 are important residues for disruption of the mitochondrial membrane potential by NSs. Therefore, these results indicate that the C terminus of CCHFV NSs triggers mitochondrial membrane permeabilization, leading to activation of caspases, which, ultimately, leads to apoptosis. Given that multiple factors contribute to apoptosis during CCHFV infection, further studies are needed to define the involvement of CCHFV NSs in regulating apoptosis in infected cells. PMID:26574543

Endocrine Disrupting Chemicals and Disease Susceptibility

Science.gov (United States)

Schug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.

2011-01-01

Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption. PMID:21899826

Microalgal cell disruption via ultrasonic nozzle spraying.

Science.gov (United States)

Wang, M; Yuan, W

2015-01-01

The objective of this study was to understand the effect of operating parameters, including ultrasound amplitude, spraying pressure, nozzle orifice diameter, and initial cell concentration on microalgal cell disruption and lipid extraction in an ultrasonic nozzle spraying system (UNSS). Two algal species including Scenedesmus dimorphus and Nannochloropsis oculata were evaluated. Experimental results demonstrated that the UNSS was effective in the disruption of microalgal cells indicated by significant changes in cell concentration and Nile red-stained lipid fluorescence density between all treatments and the control. It was found that increasing ultrasound amplitude generally enhanced cell disruption and lipid recovery although excessive input energy was not necessary for best results. The effect of spraying pressure and nozzle orifice diameter on cell disruption and lipid recovery was believed to be dependent on the competition between ultrasound-induced cavitation and spraying-generated shear forces. Optimal cell disruption was not always achieved at the highest spraying pressure or biggest nozzle orifice diameter; instead, they appeared at moderate levels depending on the algal strain and specific settings. Increasing initial algal cell concentration significantly reduced cell disruption efficiency. In all UNSS treatments, the effectiveness of cell disruption and lipid recovery was found to be dependent on the algal species treated.

Endocrine Disrupting Contaminants—Beyond the Dogma

Science.gov (United States)

Guillette, Louis J.

2006-01-01

Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

Science.gov (United States)

McIntyre, Alan; Hulikova, Alzbeta; Ledaki, Ioanna; Snell, Cameron; Singleton, Dean; Steers, Graham; Seden, Peter; Jones, Dylan; Bridges, Esther; Wigfield, Simon; Li, Ji-Liang; Russell, Angela; Swietach, Pawel; Harris, Adrian L

2016-07-01

Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven bicarbonate transporters, increased apoptosis in the cell lines tested. Finally, RNAi-mediated attenuation of SLC4A9 increased apoptosis in MDA-MB-231 breast cancer spheroids and dramatically reduced growth of MDA-MB-231 breast tumors or U87 gliomas in murine xenografts. Our findings suggest that disrupting pH homeostasis by blocking bicarbonate import might broadly relieve the common resistance of hypoxic tumors to anticancer therapy. Cancer Res; 76(13); 3744-55. ©2016 AACR. ©2016 American Association for Cancer Research.

Circadian rhythm disruption as a link between Attention-Deficit/Hyperactivity Disorder and obesity?

Science.gov (United States)

Vogel, Suzan W N; Bijlenga, Denise; Tanke, Marjolein; Bron, Tannetje I; van der Heijden, Kristiaan B; Swaab, Hanna; Beekman, Aartjan T F; Kooij, J J Sandra

2015-11-01

Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) have a high prevalence of obesity. This is the first study to investigate whether circadian rhythm disruption is a mechanism linking ADHD symptoms to obesity. ADHD symptoms and two manifestations of circadian rhythm disruption: sleep problems and an unstable eating pattern (skipping breakfast and binge eating later in the day) were assessed in participants with obesity (n= 114), controls (n= 154), and adult ADHD patients (n= 202). Participants with obesity had a higher prevalence of ADHD symptoms and short sleep on free days as compared to controls, but a lower prevalence of ADHD symptoms, short sleep on free days, and an unstable eating pattern as compared to ADHD patients.We found that participants with obesity had a similar prevalence rate of an unstable eating pattern when compared to controls. Moreover, mediation analyses showed that both sleep duration and an unstable eating pattern mediated the association between ADHD symptoms and body mass index (BMI). Our study supports the hypothesis that circadian rhythm disruption is a mechanism linking ADHD symptoms to obesity. Further research is needed to determine if treatment of ADHD and circadian rhythm disruption is effective in the prevention and treatment of obesity in patients with obesity and/or ADHD. Copyright © 2015 Elsevier Inc. All rights reserved.

The comparative study of lumbar disc disruption with MRI and CT discography

International Nuclear Information System (INIS)

Chen Xingcan; Liu Naifang; Li Xiaohong; Xu Wengen; Zou Qing; Yang Yonghong

2005-01-01

Objective: To compare MRI with CT discography (CTD) for diagnostic assessment of lumbar disc disruption. Methods: Paired comparative examination in 16 patients with chronic lower back pain without radicular pain and no disc herniation was conducted using CT or MRI. The standard of CTD classification and positive disc was formulated and the correlation between the induced lower back pain and dosage used in CTD was observed. Results: For a total of 21 discs in the 16 patients, CTD showed the disc as type 2 in 12 discs and type 5 in 1 disc with 13 positive discs, while MRI only showed the high-intensity zone of posterior annulus in 6 discs as the indirect sign of disc disruption and disc degeneration in 7 discs. Conclusion: CTD was the only method for showing the direct sign of disc disruption. The induced lower back pain was related with the type of disc disruption. MRI can show some of the indirect signs of disc disruption and CTD can show the direct sign of disc disruption. (authors)

Game-induced fatigue patterns in elite female soccer

DEFF Research Database (Denmark)

Krustrup, Peter; Zebis, Mette; Jensen, Jack Majgaard

2010-01-01

.06 +/- 0.06 seconds after the game, which was 4% slower (p game-induced effect was observed on vertical jump performance. Significant inverse correlations were observed between Yo-Yo IE2 test performance and fatigue index during the repeated sprint test both......Krustrup, P, Zebis, M, Jensen, JM, and Mohr, M. Game-induced fatigue patterns in elite female soccer. J Strength Cond Res 24(2): 437-441, 2010-The purpose was to examine the fatigue pattern of elite female soccer players after competitive games. Soccer players (n = 23) from the Danish women Premier...... League performed a countermovement vertical jump test, a repeated 30-m sprint test, and the Yo-Yo intermittent endurance level 2 (Yo-Yo IE2) test at rested state and after a competitive game. Average heart rate during the game was 86 +/- 1% of maximal heart rate with no differences between halves. Blood...

Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.

Science.gov (United States)

Honma, Kazue; Hikosaka, Maki; Mochizuki, Kazuki; Goda, Toshinao

2016-04-01

Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day. We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice. Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accβ) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD. These results indicate that the disruption of the circadian rhythm of insulin secretion by HFD intake is closely associated with the disappearance of circadian expression of lipogenic and clock genes in the liver of mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Bird populations as sentinels of endocrine disrupting chemicals.

Science.gov (United States)

Carere, Claudio; Costantini, David; Sorace, Alberto; Santucci, Daniela; Alleva, Enrico

2010-01-01

Exposure to endocrine disrupting chemicals (EDCs) is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED) at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

Transformations of visual memory induced by implied motions of pattern elements.

Science.gov (United States)

Finke, R A; Freyd, J J

1985-10-01

Four experiments measured distortions in short-term visual memory induced by displays depicting independent translations of the elements of a pattern. In each experiment, observers saw a sequence of 4 dot patterns and were instructed to remember the third pattern and to compare it with the fourth. The first three patterns depicted translations of the dots in consistent, but separate directions. Error rates and reaction times for rejecting the fourth pattern as different from the third were substantially higher when the dots in that pattern were displaced slightly forward, in the same directions as the implied motions, compared with when the dots were displaced in the opposite, backward directions. These effects showed little variation across interstimulus intervals ranging from 250 to 2,000 ms, and did not depend on whether the displays gave rise to visual apparent motion. However, they were eliminated when the dots in the fourth pattern were displaced by larger amounts in each direction, corresponding to the dot positions in the next and previous patterns in the same inducing sequence. These findings extend our initial report of the phenomenon of "representational momentum" (Freyd & Finke, 1984a), and help to rule out alternatives to the proposal that visual memories tend to undergo, at least to some extent, the transformations implied by a prior sequence of observed events.

AFM of the ultrastructural and mechanical properties of lipid-raft-disrupted and/or cold-treated endothelial cells.

Science.gov (United States)

Wu, Li; Huang, Jie; Yu, Xiaoxue; Zhou, Xiaoqing; Gan, Chaoye; Li, Ming; Chen, Yong

2014-02-01

The nonionic detergent extraction at 4 °C and the cholesterol-depletion-induced lipid raft disruption are the two widely used experimental strategies for lipid raft research. However, the effects of raft disruption and/or cold treatment on the ultrastructural and mechanical properties of cells are still unclear. Here, we evaluated the effects of raft disruption and/or cold (4 °C) treatment on these properties of living human umbilical vein endothelial cells (HUVECs). At first, the cholesterol-depletion-induced raft disruption was visualized by confocal microscopy and atomic force microscopy (AFM) in combination with fluorescent quantum dots. Next, the cold-induced cell contraction and the formation of end-branched filopodia were observed by confocal microscopy and AFM. Then, the cell-surface ultrastructures were imaged by AFM, and the data showed that raft disruption and cold treatment induced opposite effects on cell-surface roughness (a significant decrease and a significant increase, respectively). Moreover, the cell-surface mechanical properties (stiffness and adhesion force) of raft-disrupted- and/or cold-treated HUVECs were measured by the force measurement function of AFM. We found that raft disruption and cold treatment induced parallel effects on cell stiffness (increase) or adhesion force (decrease) and that the combination of the two treatments caused dramatically strengthened effects. Finally, raft disruption was found to significantly impair cell migration as previously reported, whereas temporary cold treatment only caused a slight but nonsignificant decrease in cell migration performed at physiological temperature. Although the mechanisms for causing these results might be complicated and more in-depth studies will be needed, our data may provide important information for better understanding the effects of raft disruption or cold treatment on cells and the two strategies for lipid raft research.

Fuel disruption mechanisms determined in-pile in the ACRR

International Nuclear Information System (INIS)

Wright, S.A.; Fischer, E.A.

1984-09-01

Over thirty in-pile experiments were performed to investigate fuel disruption behavior for LMFBR loss of flow (LOF) accidents. These experiments reproduced the heating transients for a variety of accidents ranging from slow LOF accidents to rapid LOF-driven-TOP accidents. In all experiments the timing and mode of the fuel disruption were observed with a high speed camera, enabling detailed comparisons with a fuel pin code, SANDPIN. This code transient intra- and inter-granular fission gas behavior to predict the macroscopic fuel behavior, such as fission gas induced swelling and frothing, cracking and breakup of solid fuel, and fuel vapor pressure driven dispersal. This report reviews the different modes of fuel disruption as seen in the experiments and then describes the mechanism responsible for the disruption. An analysis is presented that describes a set of conditions specifying the mode of fuel disruption and the heating conditions required to produce the disruption. The heating conditions are described in terms of heating rate (K/s), temperature gradient, and fuel temperature. A fuel disruption map is presented which plots heating rate as a function of fuel temperature to illustrate the different criteria for disruption. Although this approach to describing fuel disruption oversimplifies the fission gas processes modeled by SANDPIN, it does illustrate the criteria used to determine which fuel disruption mechanism is dominant and on what major fission gas parameters it depends

Quick profile-reorganization driven by helical field perturbation for suppressing tokamak major disruptions

International Nuclear Information System (INIS)

Yamazaki, K.; Kawahata, K.; Ando, R.

1986-09-01

Disruptive behavior of magnetic field configuration leading to tokamak major disruption is found to be controlled by a mild ''mini-disruption'' which is induced by the compact external modular multipole-field coils with m = 3/n = 2 dominant helical field component in the JIPP T-IIU tokamak. This mini-disruption ergodizes the m = 2/n = 1 magnetic island quickly but mildly and then prevents the profile of electron temperature from flattening. This quick profile-reorganization is effective to avoid the two-step disruption (pre- and major disuptions) responsible for the chatastrophic current termination. (author)

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice.

Science.gov (United States)

Pilz, Luísa K; Trojan, Yasmine; Quiles, Caroline L; Benvenutti, Radharani; Melo, Gabriela; Levandovski, Rosa; Hidalgo, Maria Paz L; Elisabetsky, Elaine

2015-03-01

Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30 mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.

Distinctive hippocampal and amygdalar cytoarchitectural changes underlie specific patterns of behavioral disruption following stress exposure in an animal model of PTSD.

Science.gov (United States)

Cohen, Hagit; Kozlovsky, Nitsan; Matar, Michael A; Zohar, Joseph; Kaplan, Zeev

2014-12-01

Alterations in cytoarchitecture and molecular signaling have been observed in adaptive and maladaptive responses to stress and presumably underlie the physiological and behavioral changes observed. The relationship between behavioral responses to stress exposure and changes in cytoarchitecture of subregions of the hippocampus and amygdala was investigated in an animal model of PTSD. Behaviors in elevated plus-maze and acoustic startle response tests were assessed in rats 7 days after exposure to predator scent stress. Brains were harvested 24h later. Neurons from CA1, CA3, and dentate gyrus subregions and basolateral amygdala were reconstructed and subjected to Sholl analysis and spine density estimation. Glucocorticoid receptor, brain-derived neurotrophic factor, phospho-NR1-Ser-889, phospho-GluR1-Ser-845, phospho-calcium/calmodulin dependent protein kinase II-Thy-286, post-synaptic density protein 95 and phospho-CREB-Ser-133 were evaluated in the hippocampus. Data were analyzed by retrospective classification of individual rats into three behavioral response groups. The extent and distribution of changes in the morphology of hippocampal and amygdalar dendrites was significantly associated with stress-induced behavioral response classification. Extreme (PTSD-like) behavioral disruption was associated with extensive neuronal retraction in the hippocampus and proliferation in the amygdala. Neither structure displayed such changes in minimal behavioral responders. Partial behavioral response was associated with identical changes in the hippocampus only. Patterns of change in requisite molecular signaling genes and endophenotypic markers corresponded to the structural and behavioral responses. The extent and distribution of changes in the cytoarchitecture of hippocampal and amygdalar subregions is directly related to the pattern of behavioral response of the individual to stress exposure. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Disruption problematics in segmented blanket concepts

International Nuclear Information System (INIS)

Crutzen, Y.; Fantechi, S.; Farfaletti-Casali, F.

1994-01-01

In Tokamaks, the hostile operating environment originated by plasma disruption events requires that the first wall/blanket/shield components sustain the large induced electromagnetic (EM) forces without significant structural deformation and within allowable material stresses. As a consequence there is a need to improve the safety features of the blanket design concepts satisfying the disruption problematics and to formulate guidelines on the required internal reinforcements of the blanket components. The present paper describes the recent investigations on blanket reinforcement systems needed in order to optimize the first-wall/blanket/shield structural design for next step and commercial fusion reactors in the context of ITER, DEMO and SEAFP activities

Regulated Assembly of Vacuolar ATPase Is Increased during Cluster Disruption-induced Maturation of Dendritic Cells through a Phosphatidylinositol 3-Kinase/mTOR-dependent Pathway*

Science.gov (United States)

Liberman, Rachel; Bond, Sarah; Shainheit, Mara G.; Stadecker, Miguel J.; Forgac, Michael

2014-01-01

The vacuolar (H+)-ATPases (V-ATPases) are ATP-driven proton pumps composed of a peripheral V1 domain and a membrane-embedded V0 domain. Regulated assembly of V1 and V0 represents an important regulatory mechanism for controlling V-ATPase activity in vivo. Previous work has shown that V-ATPase assembly increases during maturation of bone marrow-derived dendritic cells induced by activation of Toll-like receptors. This increased assembly is essential for antigen processing, which is dependent upon an acidic lysosomal pH. Cluster disruption of dendritic cells induces a semi-mature phenotype associated with immune tolerance. Thus, semi-mature dendritic cells are able to process and present self-peptides to suppress autoimmune responses. We have investigated V-ATPase assembly in bone marrow-derived, murine dendritic cells and observed an increase in assembly following cluster disruption. This increased assembly is not dependent upon new protein synthesis and is associated with an increase in concanamycin A-sensitive proton transport in FITC-loaded lysosomes. Inhibition of phosphatidylinositol 3-kinase with wortmannin or mTORC1 with rapamycin effectively inhibits the increased assembly observed upon cluster disruption. These results suggest that the phosphatidylinositol 3-kinase/mTOR pathway is involved in controlling V-ATPase assembly during dendritic cell maturation. PMID:24273170

Engineering analysis of TFTR disruption

Energy Technology Data Exchange (ETDEWEB)

Murray, J.G.; Rothe, K.E.; Bronner, G.

1984-09-01

This report covers an engineering approach quantifying the currents, forces, and times, as well as plasma position, for the worst-case disruption based on engineerign circuit assumptions for the plasma. As the plasma moves toward the wall during the current-decay phase of disruption, the wall currents affect the rate of movement and, hence, the decay time. The calculated structure-induced currents differ considerably from those calculated using a presently available criterion, which specifies that the plasma remains stationary in the center of the torus while decaying in 10 ms. This report outlines the method and basis for the engineering calculation used to determine the current and forces as a function of the circuit characteristics. It provides specific calculations for the Tokamak Fusion Test Reactor (TFTR) with variations in parameters such as the thermal decay time, the torus resistance, and plasma temperature during the current decay. The study reviews possible ways to reduce the disruption damage of TFTR by reducing the magnitude of the plasma external field energy that is absorbed by the plasma during the current decay.

Engineering analysis of TFTR disruption

International Nuclear Information System (INIS)

Murray, J.G.; Rothe, K.E.; Bronner, G.

1984-09-01

This report covers an engineering approach quantifying the currents, forces, and times, as well as plasma position, for the worst-case disruption based on engineerign circuit assumptions for the plasma. As the plasma moves toward the wall during the current-decay phase of disruption, the wall currents affect the rate of movement and, hence, the decay time. The calculated structure-induced currents differ considerably from those calculated using a presently available criterion, which specifies that the plasma remains stationary in the center of the torus while decaying in 10 ms. This report outlines the method and basis for the engineering calculation used to determine the current and forces as a function of the circuit characteristics. It provides specific calculations for the Tokamak Fusion Test Reactor (TFTR) with variations in parameters such as the thermal decay time, the torus resistance, and plasma temperature during the current decay. The study reviews possible ways to reduce the disruption damage of TFTR by reducing the magnitude of the plasma external field energy that is absorbed by the plasma during the current decay

Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides).

Science.gov (United States)

Richter, Catherine A; Martyniuk, Christopher J; Annis, Mandy L; Brumbaugh, William G; Chasar, Lia C; Denslow, Nancy D; Tillitt, Donald E

2014-07-01

Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates. Published by Elsevier Inc.

Methylmercury-induced changes in gene transcription associated with neuroendocrine disruption in largemouth bass (Micropterus salmoides)

Science.gov (United States)

Richter, Catherine A.; Martyniuk, Christopher J.; Annis, Mandy L.; Brumbaugh, William G.; Chasar, Lia C.; Denslow, Nancy D.; Tillitt, Donald E.

2014-01-01

Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates.

Metabolic effects of bariatric surgery in mouse models of circadian disruption.

Science.gov (United States)

Arble, D M; Sandoval, D A; Turek, F W; Woods, S C; Seeley, R J

2015-08-01

Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity. Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption. VSG led to a reduction in body weight and fat mass in both Clock(Δ19) mutant and constant-light mouse models (Pdisruption. Interestingly, the decrease in body weight occurred without altering diurnal feeding or activity patterns (P>0.05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (Pdisruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, as the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption.

Bird populations as sentinels of endocrine disrupting chemicals

Directory of Open Access Journals (Sweden)

Claudio Carere

2010-03-01

Full Text Available Exposure to endocrine disrupting chemicals (EDCs is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells.

Science.gov (United States)

Xia, Lijie; Wu, Yanling; Kang, Su; Ma, Ji; Yang, Jianhua; Zhang, Fuchun

2014-10-01

Antimicrobial peptides exist in the non-specific immune system of organism and participate in the innate host defense of each species. CecropinXJ, a cationic antimicrobial peptide, possesses potent anticancer activity and acts preferentially on cancer cells instead of normal cells, but the mechanism of cancer cell death induced by cecropinXJ remains largely unknown. This study was performed to investigate the cytoskeleton-disrupting effects of cecropinXJ on human esophageal carcinoma cell line Eca109 using scanning electron microscopy observation, fluorescence imaging, cell migration and invasion assays, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The electronic microscope and fluorescence imaging observation suggested that cecropinXJ could result in morphological changes and induce damage to microtubules and actin of Eca109 cells in a dose-dependent manner. The cell migration and invasion assays demonstrated that cecropinXJ could inhibit migration and invasion of tumor cells. Western blot and qRT-PCR analysis showed that there was obvious correlation between microtubule depolymerization and actin polymerization induced by cecropinXJ. Moreover, cecropinXJ might also cause decreased expression of α-actin, β-actin, γ-actin, α-tubulin, and β-tubulin genes in concentration- and time-dependent manners. In summary, this study indicates that cecropinXJ triggers cytotoxicity in Eca109 cells through inducing the cytoskeleton destruction and regulating the expression of cytoskeleton proteins. This cecropinXJ-mediated cytoskeleton-destruction effect is instrumental in our understanding of the detailed action of antimicrobial peptides in human cancer cells and cecropinXJ might be a potential therapeutic agent for the treatment of cancer in the future. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology

Structural responses to plasma disruptions in toroidal shells

International Nuclear Information System (INIS)

Tillack, M.S.; Kazimi, M.S.; Lidsky, L.M.

1985-01-01

The induced pressures, stresses and strains in unrestrained axisymmetric toroidal shells are studied to scope the behavior of tokamak first walls during plasma disruptions. The modeling includes a circuit analog representation of the shell to solve for induced currents and pressures, and a separate quasi-static 1-D finite element solution for the mechanical response. This work demonstrates that the stresses in tokamkak first walls due to plasma disruption may be large, but to first order will not cause failure in the bulk structure. However, stress concentrations at structural supports and discontinuities together with resonant effects can result in large enhancements of the stresses, which could contribute to plastic deformation or failure when added to the already large steady state thermal and pressure loading of the first wall

Obesity promotes oxidative stress and exacerbates blood-brain barrier disruption after high-intensity exercise

Directory of Open Access Journals (Sweden)

Hee-Tae Roh

2017-06-01

Conclusion: Our study suggests that episodic vigorous exercise can increase oxidative stress and blood neurotrophic factor levels and induce disruption of the BBB. Moreover, high levels of neurotrophic factor in the blood after exercise in the obese group may be due to BBB disruption, and it is assumed that oxidative stress was the main cause of this BBB disruption.

Skin barrier disruption by acetone: observations in a hairless mouse skin model

NARCIS (Netherlands)

Rissmann, R.; Oudshoorn, M.H.M.; Hennink, W.E.; Ponec, M.; Bouwstra, J.A.

2009-01-01

To disrupt the barrier function of the skin, different in vivo methods have been established, e.g., by acetone wiping or tape-stripping. In this study, the acetone-induced barrier disruption of hairless mice was investigated in order to establish a reliable model to study beneficial, long-term

Poor quality of life, depressed mood, and memory impairment may be mediated by sleep disruption in patients with Addison's disease.

Science.gov (United States)

Henry, Michelle; Wolf, Pedro S A; Ross, Ian L; Thomas, Kevin G F

2015-11-01

Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. In fact, hydrocortisone replacement in AD patients likely induces disrupted sleep. Given that healthy sleep plays an important role in improving quality of life, optimizing cognition, and ensuring affect regulation, the aim of this study was to investigate whether poor quality of life, mood alterations, and memory complaints reported by AD patients are associated with their disrupted sleep patterns. Sixty patients with AD and 60 matched healthy controls completed a battery of self-report questionnaires assessing perceived physical and mental health (Short-Form 36), mood (Beck Depression Inventory-II), sleep quality (Pittsburgh Sleep Quality Index), and cognition (Cognitive Failures Questionnaire). A latent variable model revealed that although AD had a significant direct effect on quality of life, the indirect effect of sleep was significantly greater. Furthermore, although AD had no direct effect on cognitive functioning, the indirect effect of sleep was significant. The overall model showed a good fit (comparative fit index = 0.91, root mean square of approximation = 0.09, and standardized root mean square residual = 0.05). Our findings suggest that disrupted sleep, and not the disease per se, may induce poor quality of life, memory impairment, and affect dysregulation in patients with AD. We think that improving sleep architecture may improve cognitive, affective, and physical functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Histone Deacetylase Inhibition Facilitates Massed Pattern-Induced Synaptic Plasticity and Memory

Science.gov (United States)

Pandey, Kiran; Sharma, Kaushik P.; Sharma, Shiv K.

2015-01-01

Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well…

Enhanced tumor cell killing following BNCT with hyperosmotic mannitol-induced blood-brain barrier disruption and intracarotid injection of boronophenylalanine

International Nuclear Information System (INIS)

Hsieh, C.H.; Hwang, J.J.; Chen, F.D.; Liu, R.S.; Liu, H.M.; Hsueh, Y.W.; Kai, J.J.

2006-01-01

The delivery of boronophenylalanine (BPA) by means of intracarotid injection combined with opening the blood-brain barrier (BBB) have been shown significantly enhanced the tumor boron concentration and the survival time of glioma-bearing rats. However, no direct evidence demonstrates whether this treatment protocol can enhance the cell killing of tumor cells or infiltrating tumor cells and the magnitude of enhanced cell killing. The purpose of the present study was to determine if the tumor cell killing of boron neutron capture therapy could be enhanced by hyperosmotic mannitol-induced BBB disruption using BPA-Fr as the capture agent. F98 glioma-bearing rats were injected intravenously or intracarotidly with BPA at doses of 500 mg/kg body weight (b.w.) and with or without mannitol-induced hyperosmotic BBB disruption. The rats were irradiated with an epithermal neutron beam at the reactor of National Tsing-Hua University (THOR). After neutron beam irradiation, the rats were euthanized and the ipsilateral brains containing intracerebral F98 glioma were removed to perform in vivo/in vitro soft agar clonogenic assay. The results demonstrate BNCT with optimizing the delivery of BPA by means of intracarotid injection combined with opening the BBB by infusing a hyperosmotic solution of mannitol significantly enhanced the cell killing of tumor cells and infiltrating tumor cells, the tumor boron concentration and the boron ratio of tumor to normal brain tissues. (author)

Tremor pattern differentiates drug-induced resting tremor from Parkinson disease.

Science.gov (United States)

Nisticò, R; Fratto, A; Vescio, B; Arabia, G; Sciacca, G; Morelli, M; Labate, A; Salsone, M; Novellino, F; Nicoletti, A; Petralia, A; Gambardella, A; Zappia, M; Quattrone, A

2016-04-01

DAT-SPECT, is a well-established procedure for distinguishing drug-induced parkinsonism from Parkinson's disease (PD). We investigated the usefulness of blink reflex recovery cycle (BRrc) and of electromyographic parameters of resting tremor for the differentiation of patients with drug-induced parkinsonism with resting tremor (rDIP) from those with resting tremor due to PD. This was a cross-sectional study. In 16 patients with rDIP and 18 patients with PD we analysed electrophysiological parameters (amplitude, duration, burst and pattern) of resting tremor. BRrc at interstimulus intervals (ISI) of 100, 150, 200, 300, 400, 500 and 750 msec was also analysed in patients with rDIP, patients with PD and healthy controls. All patients and controls underwent DAT-SPECT. Rest tremor amplitude was higher in PD patients than in rDIP patients (p tremor showed a synchronous pattern in all patients with rDIP, whereas it had an alternating pattern in all PD patients (p tremor can be considered a useful investigation for differentiating rDIP from PD. Copyright © 2016. Published by Elsevier Ltd.

"Targeted disruption of the epithelial-barrier by Helicobacter pylori"

Directory of Open Access Journals (Sweden)

Wroblewski Lydia E

2011-11-01

Full Text Available Abstract Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier.

Experiments to Measure Hydrogen Release from Graphite Walls During Disruptions in DIII-D

International Nuclear Information System (INIS)

Hollmann, E.M.; Pablant, N.A.; Rudakov, D.L.; Boedo, J.A.; Brooks, N.H.; Jernigan, Thomas C.; Pigarov, A.Y.

2009-01-01

Spectroscopy and wall the bake-out measurements are performed in the DIII-D tokamak to estimate the amount of hydrogen stored in and released from the walls during disruptions. Both naturally occurring disruptions and disruptions induced by massive gas injection (MGI) are investigated. The measurements indicate that both types of disruptions cause a net release of order 10(21) hydrogen (or deuterium) atoms from the graphite walls. This is comparable to the pre-disruptions plasma particle inventory, so the released hydrogen is important for accurate modeling of disruptions. However, the amount of hydrogen released is small compared to the total saturated wall inventory of order 10(22)-10(23), So it appears that many disruptions are necessary to provide full pump-out of the vessel walls. (C) 2009 Published by Elsevier B.V.

Exogenous retinoic acid induces digit reduction in opossums (Monodelphis domestica) by disrupting cell death and proliferation, and apical ectodermal ridge and zone of polarizing activity function.

Science.gov (United States)

Molineaux, Anna C; Maier, Jennifer A; Schecker, Teresa; Sears, Karen E

2015-03-01

Retinoic acid (RA) is a vitamin A derivative. Exposure to exogenous RA generates congenital limb malformations (CLMs) in species from frogs to humans. These CLMs include but are not limited to oligodactyly and long-bone hypoplasia. The processes by which exogenous RA induces CLMs in mammals have been best studied in mouse, but as of yet remain unresolved. We investigated the impact of exogenous RA on the cellular and molecular development of the limbs of a nonrodent model mammal, the opossum Monodelphis domestica. Opossums exposed to exogenous retinoic acid display CLMs including oligodactly, and results are consistent with opossum development being more susceptible to RA-induced disruptions than mouse development. Exposure of developing opossums to exogenous RA leads to an increase in cell death in the limb mesenchyme that is most pronounced in the zone of polarizing activity, and a reduction in cell proliferation throughout the limb mesenchyme. Exogenous RA also disrupts the expression of Shh in the zone of polarizing activity, and Fgf8 in the apical ectodermal ridge, and other genes with roles in the regulation of limb development and cell death. Results are consistent with RA inducing CLMs in opossum limbs by disrupting the functions of the apical ectodermal ridge and zone of polarizing activity, and driving an increase in cell death and reduction of cell proliferation in the mesenchyme of the developing limb. © 2015 Wiley Periodicals, Inc.

Mating Disruption for the 21st Century: Matching Technology With Mechanism.

Science.gov (United States)

Miller, James R; Gut, Larry J

2015-06-01

inverse of catch is plotted against density of pheromone dispensers; and, a recurving plot when catch is plotted against density of pheromone dispensers x catch. Hybrid profiles are possible when some males within the population begin the activity period already incapacitated, while those not preexposed have the capacity to respond either to traps or pheromone dispensers. Competitive mechanisms include competitive attraction, induced allopatry, and induced arrestment. Noncompetitive mechanisms include desensitization and inhibition, induced allochrony, suppressed calling and mating, camouflage, and sensory imbalance. Examples of the various disruption types within the two major categories and suggested tactics for differentiating among them are offered as seven case studies of the disruption of important pest species using various formulations are analyzed in depth. We point out how economic optimizations may be achieved once the principal and contributory causes of disruption are proven. Hopefully, these insights will pave the way to a broader and more reliable usage of this environmentally friendly pest management tactic. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Edge enhancement improves disruptive camouflage by emphasising false edges and creating pictorial relief.

Science.gov (United States)

Egan, John; Sharman, Rebecca J; Scott-Brown, Kenneth C; Lovell, Paul George

2016-12-06

Disruptive colouration is a visual camouflage composed of false edges and boundaries. Many disruptively camouflaged animals feature enhanced edges; light patches are surrounded by a lighter outline and/or a dark patches are surrounded by a darker outline. This camouflage is particularly common in amphibians, reptiles and lepidopterans. We explored the role that this pattern has in creating effective camouflage. In a visual search task utilising an ultra-large display area mimicking search tasks that might be found in nature, edge enhanced disruptive camouflage increases crypsis, even on substrates that do not provide an obvious visual match. Specifically, edge enhanced camouflage is effective on backgrounds both with and without shadows; i.e. this is not solely due to background matching of the dark edge enhancement element with the shadows. Furthermore, when the dark component of the edge enhancement is omitted the camouflage still provided better crypsis than control patterns without edge enhancement. This kind of edge enhancement improved camouflage on all background types. Lastly, we show that edge enhancement can create a perception of multiple surfaces. We conclude that edge enhancement increases the effectiveness of disruptive camouflage through mechanisms that may include the improved disruption of the object outline by implying pictorial relief.

Time delay induced different synchronization patterns in repulsively coupled chaotic oscillators

Science.gov (United States)

Yao, Chenggui; Yi, Ming; Shuai, Jianwei

2013-09-01

Time delayed coupling plays a crucial role in determining the system's dynamics. We here report that the time delay induces transition from the asynchronous state to the complete synchronization (CS) state in the repulsively coupled chaotic oscillators. In particular, by changing the coupling strength or time delay, various types of synchronous patterns, including CS, antiphase CS, antiphase synchronization (ANS), and phase synchronization, can be generated. In the transition regions between different synchronous patterns, bistable synchronous oscillators can be observed. Furthermore, we show that the time-delay-induced phase flip bifurcation is of key importance for the emergence of CS. All these findings may light on our understanding of neuronal synchronization and information processing in the brain.

Peptide YY induces characteristic meal patterns of aged mice.

Science.gov (United States)

Mogami, Sachiko; Yamada, Chihiro; Fujitsuka, Naoki; Hattori, Tomohisa

2017-11-01

Changes in eating behavior occur in the elderly due to oral and swallowing dysfunctions. We aimed to clarify the difference between basal meal patterns of young and aged mice in relation to appetite regulating hormones. Thirty two of young (7-week-old) and aged (23-25-month-old) C57BL/6 male mice were acclimated to a single housing and then transferred to a highly sensitive automated feeding monitoring device. Feeding behavior was monitored from the onset of the dark phase after habituation to the device. Plasma peptide YY (PYY) levels were assessed under the several feeding status or after treatment of PYY. PYY and its receptor (NPY Y2 receptor, Y2R) antagonist were intraperitoneally administered 30min before the monitoring. Although the basal 24-h meal amounts did not differ by age, the total meal time and frequency of minimum feeding activity (bout) were significantly increased and the average bout size and time per bout were significantly decreased in aged mice. PYY dynamics were abnormal and the temporal reduction in food intake by exogenous PYY was more prominent in aged mice than in young mice. PYY administration to young mice induced aged-like meal patterns, and Y2R antagonist administration to aged mice induced young-like meal patterns. Aged mice exhibited characteristic meal patterns probably due to PYY metabolism dysfunction and/or enhanced PYY-Y2R signaling, suggesting a novel method for assessing eating difficulties in aged animals and a potential target for the remedy. Copyright © 2017 Elsevier Inc. All rights reserved.

Irradiation-induced patterning in dilute Cu–Fe alloys

International Nuclear Information System (INIS)

Stumphy, B.; Chee, S.W.; Vo, N.Q.; Averback, R.S.; Bellon, P.; Ghafari, M.

2014-01-01

Compositional patterning in dilute Cu 1−x Fe x (x ≈ 12%) induced by 1.8 MeV Kr + irradiation was studied as a function of temperature using atom probe tomography. Irradiation near room temperature led to homogenization of the sample, whereas irradiation at 300 °C and above led to precipitation and macroscopic coarsening. Between these two temperatures the irradiated alloys formed steady state patterns of composition where precipitates grew to a fixed size. The size in this regime increased somewhat with temperature. It was also observed that the steady state concentrations of Fe in Cu matrix and Cu in the Fe precipitates both greatly exceeded their equilibrium solubilities, with the degree of supersaturation in each phase decreasing with increasing temperature. In the macroscopic coarsening regime, the Fe-rich precipitates showed indications of a “cherry-pit” structure, with Cu precipitates forming within the Fe precipitates. In the patterning regime, interfaces between Fe-rich precipitates and the Cu-rich matrix were irregular and diffuse

Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in Melatonin Induction in Plants

Directory of Open Access Journals (Sweden)

Hyoung-Yool Lee

2017-10-01

Full Text Available Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl2 or AlCl3 and monitored the structures of subcellular organelles—such as chloroplasts, mitochondria, and the endoplasmic reticulum (ER—using confocal microscopic analysis. Unlike AlCl3 treatment, CdCl2 (0.5 mM treatment significantly disrupted chloroplasts, mitochondria, and ER. In theory, the disruption of chloroplasts enabled chloroplast-expressed serotonin N-acetyltransferase (SNAT to encounter serotonin in the cytoplasm, leading to the synthesis of N-acetylserotonin followed by melatonin synthesis. In fact, the disruption of chloroplasts by cadmium, not by aluminum, gave rise to a huge induction of melatonin in rice leaves, which suggests that cadmium-treated chloroplast disruption plays an important role in inducing melatonin in plants by removing physical barriers, such as chloroplast double membranes, allowing SNAT to gain access to the serotonin substrate enriched in the cytoplasm.

Business Model as an Inducer of Disruptive Innovations: The Case of Gol Airlines

Directory of Open Access Journals (Sweden)

Sirlei de Almeida Pereira

2015-10-01

Full Text Available This study was undertaken to investigate the premises that the success of disruptive innovation is related to the business model adopted by organizations. An analysis of five business models from the literature review - Bovet and Martha (2000, Applegate (2001, Chesbrough and Rosenbloom (2002, Osterwalder and Pigneur (2010, and Rodrigues, Maccari and Lenzi (2012 – was conducted based on the case of the Brazilian Gol Airlines who is recognized as a success business that promoted a disruptive innovation. The results suggest that the assertive choice of the business model can leverage innovation processes, and two of the models listed are adherence to the case studied. Keywords: Disruptive Innovation; Business Model; Innovation Elements; Strategy; Gol Airlines.

Gold nanoparticles administration induced prominent inflammatory, central vein intima disruption, fatty change and Kupffer cells hyperplasia

Directory of Open Access Journals (Sweden)

Abdelhalim Mohamed

2011-08-01

Full Text Available Abstract Background Advances in nanotechnology have identified promising candidates for many biological, biomedical and biomedicine applications. They are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the effects of administration of gold nanoparticles (GNPs on inflammatory cells infiltration, central vein intima disruption, fatty change, and Kupffer cells hyperplasia in the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. Methods A total of 70 healthy male Wistar-Kyoto rats were exposed to GNPs received 50 or 100 μl of GNPs infusion of 10, 20 and 50 nm GNPs for 3 or 7 days. Animals were randomly divided into groups, 12 GNPs-treated rats groups and one control group (NG. Groups 1, 2 and 3 received infusion of 50 μl GNPs of size 10 nm (3 or 7 days, size 20 nm (3 or 7 days and 50 nm (3 or 7 days, respectively; while groups 4, 5 and 6 received infusion of 100 μl GNPs of size 10 nm, size 20 nm and 50 nm, respectively. Results In comparison with respective control rats, exposure to GNPs doses has produced alterations in the hepatocytes, portal triads and sinusoids. The alterations in the hepatocytes were mainly vacuolar to hydropic degeneration, cytopasmic hyaline vacuolation, polymorphism, binucleation, karyopyknosis, karyolysis, karyorrhexis and necrosis. In addition, inflammatory cell infiltration, Kupffer cells hyperplasia, central veins intima disruption, hepatic strands dilatation and occasional fatty change together with a loss of normal architechiture of hepatic strands were also seen. Conclusions The alterations induced by the administration of GNPs were size-dependent with smaller ones induced more affects and related with time exposure of GNPs. These alterations might be an indication of injured hepatocytes due to GNPs toxicity that became unable to deal with the

Investigating Disruption

DEFF Research Database (Denmark)

Lundgaard, Stine Schmieg; Rosenstand, Claus Andreas Foss

This book shares knowledge collected from 2015 and onward within the Consortium for Digital Disruption anchored at Aalborg University (www.dd.aau.dk). Evidenced by this publication, the field of disruptive innovation research has gone through several stages of operationalizing the theory. In recent...... years, researchers are increasingly looking back towards the origins of the theory in attempts to cure it from its most obvious flaws. This is especially true for the use of the theory in making predictions about future disruptions. In order to continue to develop a valuable theory of disruption, we...... find it useful to first review what the theory of disruptive innovation initially was, how it has developed, and where we are now. A cross section of disruptive innovation literature has been reviewed in order to form a general foundation from which we might better understand the changing world...

Climate induced changes in the circulation and dispersal patterns of ...

Indian Academy of Sciences (India)

Climate induced changes in the circulation and dispersal patterns of the fluvial sources during late Quaternary in the middle Bengal Fan ... in 14C dated box cores from the eastern, the central and the western regions were studied to determine ...

Axisymmetric MHD simulation of ITB crash and following disruption dynamics of Tokamak plasmas with high bootstrap current

International Nuclear Information System (INIS)

Takei, Nahoko; Tsutsui, Hiroaki; Tsuji-Iio, Shunji; Shimada, Ryuichi; Nakamura, Yukiharu; Kawano, Yasunori; Ozeki, Takahisa; Tobita, Kenji; Sugihara, Masayoshi

2004-01-01

Axisymmetric MHD simulation using the Tokamak Simulation Code demonstrated detailed disruption dynamics triggered by a crash of internal transport barrier in high bootstrap current, high β, reversed shear plasmas. Self-consistent time-evolutions of ohmic current bootstrap current and induced loop voltage profiles inside the disrupting plasma were shown from a view point of disruption characterization and mitigation. In contrast with positive shear plasmas, a particular feature of high bootstrap current reversed shear plasma disruption was computed to be a significant change of plasma current profile, which is normally caused due to resistive diffusion of the electric field induced by the crash of internal transport barrier in a region wider than the internal transport barrier. Discussion based on the simulation results was made on the fastest record of the plasma current quench observed in JT-60U reversed shear plasma disruptions. (author)

Microarray analysis identifies keratin loci as sensitive biomarkers for thyroid hormone disruption in the salamander Ambystoma mexicanum.

Science.gov (United States)

Page, Robert B; Monaghan, James R; Samuels, Amy K; Smith, Jeramiah J; Beachy, Christopher K; Voss, S Randal

2007-02-01

Ambystomatid salamanders offer several advantages for endocrine disruption research, including genomic and bioinformatics resources, an accessible laboratory model (Ambystoma mexicanum), and natural lineages that are broadly distributed among North American habitats. We used microarray analysis to measure the relative abundance of transcripts isolated from A. mexicanum epidermis (skin) after exogenous application of thyroid hormone (TH). Only one gene had a >2-fold change in transcript abundance after 2 days of TH treatment. However, hundreds of genes showed significantly different transcript levels at days 12 and 28 in comparison to day 0. A list of 123 TH-responsive genes was identified using statistical, BLAST, and fold level criteria. Cluster analysis identified two groups of genes with similar transcription patterns: up-regulated versus down-regulated. Most notably, several keratins exhibited dramatic (1000 fold) increases or decreases in transcript abundance. Keratin gene expression changes coincided with morphological remodeling of epithelial tissues. This suggests that keratin loci can be developed as sensitive biomarkers to assay temporal disruptions of larval-to-adult gene expression programs. Our study has identified the first collection of loci that are regulated during TH-induced metamorphosis in a salamander, thus setting the stage for future investigations of TH disruption in the Mexican axolotl and other salamanders of the genus Ambystoma.

Digital Disruption

DEFF Research Database (Denmark)

Rosenstand, Claus Andreas Foss

det digitale domæne ud over det niveau, der kendetegner den nuværende debat, så præsenteres der ny viden om digital disruption. Som noget nyt udlægges Clayton Christens teori om disruptiv innovation med et særligt fokus på små organisationers mulighed for eksponentiel vækst. Specielt udfoldes...... forholdet mellem disruption og den stadig accelererende digitale udvikling i konturerne til ny teoridannelse om digital disruption. Bogens undertitel ”faretruende og fascinerende forandringer” peger på, at der er behov for en nuanceret debat om digital disruption i modsætning til den tone, der er slået an i...... videre kalder et ”disruption-råd”. Faktisk er rådet skrevet ind i 2016 regeringsgrundlaget for VLK-regeringen. Disruption af organisationer er ikke et nyt fænomen; men hastigheden, hvormed det sker, er stadig accelererende. Årsagen er den globale mega-trend: Digitalisering. Og derfor er specielt digital...

Surface-induced patterns from evaporating droplets of aqueous carbon nanotube dispersions

KAUST Repository

Zeng, Hongbo; Kristiansen, Kai De Lange; Wang, Peng; Bergli, Joakim; Israelachvili, Jacob N.

2011-01-01

Evaporation of aqueous droplets of carbon nanotubes (CNTs) coated with a physisorbed layer of humic acid (HA) on a partially hydrophilic substrate induces the formation of a film of CNTs. Here, we investigate the role that the global geometry of the substrate surfaces has on the structure of the CNT film. On a flat mica or silica surface, the evaporation of a convex droplet of the CNT dispersion induces the well-known "coffee ring", while evaporation of a concave droplet (capillary meniscus) of the CNT dispersion in a wedge of two planar mica sheets or between two crossed-cylinder sheets induces a large area (>mm 2) of textured or patterned films characterized by different short- and long-range orientational and positional ordering of the CNTs. The resulting patterns appear to be determined by two competing or cooperative sedimentation mechanisms: (1) capillary forces between CNTs giving micrometer-sized filaments parallel to the boundary line of the evaporating droplet and (2) fingering instability at the boundary line of the evaporating droplet and subsequent pinning of CNTs on the surface giving micrometer-sized filaments of CNTs perpendicular to this boundary line. The interplay between substrate surface geometry and sedimentation mechanisms gives an extra control parameter for manipulating patterns of self-assembling nanoparticles at substrate surfaces. © 2011 American Chemical Society.

Surface-induced patterns from evaporating droplets of aqueous carbon nanotube dispersions

KAUST Repository

Zeng, Hongbo

2011-06-07

Evaporation of aqueous droplets of carbon nanotubes (CNTs) coated with a physisorbed layer of humic acid (HA) on a partially hydrophilic substrate induces the formation of a film of CNTs. Here, we investigate the role that the global geometry of the substrate surfaces has on the structure of the CNT film. On a flat mica or silica surface, the evaporation of a convex droplet of the CNT dispersion induces the well-known "coffee ring", while evaporation of a concave droplet (capillary meniscus) of the CNT dispersion in a wedge of two planar mica sheets or between two crossed-cylinder sheets induces a large area (>mm 2) of textured or patterned films characterized by different short- and long-range orientational and positional ordering of the CNTs. The resulting patterns appear to be determined by two competing or cooperative sedimentation mechanisms: (1) capillary forces between CNTs giving micrometer-sized filaments parallel to the boundary line of the evaporating droplet and (2) fingering instability at the boundary line of the evaporating droplet and subsequent pinning of CNTs on the surface giving micrometer-sized filaments of CNTs perpendicular to this boundary line. The interplay between substrate surface geometry and sedimentation mechanisms gives an extra control parameter for manipulating patterns of self-assembling nanoparticles at substrate surfaces. © 2011 American Chemical Society.

Monocrotophos, an organophosphorus insecticide, disrupts the expression of HpNetrin and its receptor neogenin during early development in the sea urchin (Hemicentrotus pulcherrimus).

Science.gov (United States)

Zhang, Xiaona; Xu, Lei; Tian, Hua; Wang, Cuicui; Wang, Wei; Ru, Shaoguo

2017-09-01

Netrins, chemotropic guidance cues, can guide the extension of serotonergic axons by binding to netrin receptors during neural development. However, little is known about whether disruption of netrin signaling is involved in the mechanisms by which organophosphorus pesticides affect serotonergic nervous system (SNS) development. In this study, we evaluated the effects of the pesticide monocrotophos (MCP) on the expression patterns of HpNetrin and its receptor neogenin as well as on the intracellular calcium ion (Ca 2+ ) levels in Hemicentrotus pulcherrimus (sea urchin) by exposing fertilized embryos to 0, 0.01, 0.10, and 1.00mg/L MCP. The results showed that MCP disrupted HpNetrin and neogenin expression at different developmental stages in H. pulcherrimus and that Ca 2+ appeared to be involved in the MCP-induced developmental neurotoxicity. Specifically, the lower concentrations of MCP elevated HpNetrin and neogenin transcription, resulting in higher intracellular Ca 2+ levels during the early developmental stages in the sea urchin; this may affect netrin-directed cell migration/axon extension and subsequently disrupt serotonergic axon branching and synapse formation. In contrast, 1.00mg/L MCP exhibited an inhibitory effect on HpNetrin and neogenin transcription. This finding implies that the regulatory roles of these factors may be diminished during early development, thereby causing developmental defects in the sea urchin. Collectively, our results provide a basis for exploring the involvement of netrin and neogenin in the organophosphate-induced disruption of the SNS during development. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of music on repetitive disruptive vocalizations of persons with dementia.

Science.gov (United States)

Casby, J A; Holm, M B

1994-10-01

This study examined the effect of classical music and favorite music on the repetitive disruptive vocalizations of long-term-care facility (LTCF) residents with dementia of the Alzheimer's type (DAT). Three subjects diagnosed with DAT who had a history of repetitive disruptive vocalizations were selected for the study. Three single-subject withdrawal designs (ABA, ACA, and ABCA) were used to assess subjects' repetitive disruptive vocalizations during each phase: no intervention (A); relaxing, classical music (B); and favorite music (C). Classical music and favorite music significantly decreased the number of vocalizations in two of the three subjects (p < .05). These findings support a method that was effective in decreasing the disruptive vocalization pattern common in those with DAT in the least restrictive manner, as mandated by the Omnibus Budget Reconciliation Act of 1987.

Patterns of Seismicity Associated with USGS Identified Areas of Potentially Induced Seismicity.

Science.gov (United States)

Barnes, Caitlin; Halihan, Todd

2018-03-13

A systematic review across U.S. Geological Survey (USGS) identified potentially induced seismic locations was conducted to discover seismic distance patterns and trends over time away from injection disposal wells. Previous research indicates a 10 km (6 miles) average where the majority of induced seismicity is expected to occur within individual locations, with some areas reporting a larger radius of 35 km (22 miles) to over 70 km (43 miles). This research analyzed earthquake occurrences within nine USGS locations where specified wells were identified as contributors to induced seismicity to determine distance patterns from disposal wells or outward seismic migration over time using established principles of hydrogeology. Results indicate a radius of 31.6 km (20 miles) where 90% of felt earthquakes occur among locations, with the closest proximal felt seismic events, on average, occurring 3 km (1.9 miles) away from injection disposal wells. The results of this research found distance trends across multiple locations of potentially induced seismicity. © 2018, National Ground Water Association.

Protective effects of resveratrol on ethanol-induced apoptosis in embryonic stem cells and disruption of embryonic development in mouse blastocysts

International Nuclear Information System (INIS)

Huang, L.-H.; Shiao, N.-H.; Hsuuw, Y.-D.; Chan, W.-H.

2007-01-01

Previous studies have established that ethanol induces apoptosis, but the precise molecular mechanisms are currently unclear. Here, we show that 0.3-1.0% (w/v) ethanol induces apoptosis in mouse blastocysts and that resveratrol, a grape-derived phytoalexin with known antioxidant and anti-inflammatory properties, prevents ethanol-induced apoptosis and inhibition of cell proliferation. Moreover, ethanol-treated blastocysts show normal levels of implantation on culture dishes in vitro but a reduced ability to reach the later stages of embryonic development. Pretreatment with resveratrol prevented ethanol-induced disruption of embryonic development in vitro and in vivo. In an in vitro cell-based assay, we further found that ethanol increases the production of reactive oxygen species in ESC-B5 embryonic stem cells, leading to an increase in the intracellular concentrations of cytoplasmic free Ca 2+ and NO, loss of mitochondrial membrane potential, mitochondrial release of cytochrome c, activation of caspase-9 and -3, and apoptosis. These changes were blocked by pretreatment with resveratrol. Based on these results, we propose a model for the protective effect of resveratrol on ethanol-induced cell injury in blastocysts and ESC-B5 cells

Tidal-Induced Ocean Dynamics as Cause of Enceladus' Tiger Stripe Pattern

Science.gov (United States)

Vermeersen, B. L.; Maas, L. R.; van Oers, S.; Rabitti, A.; Jara-Orue, H.

2013-12-01

One of the most peculiar features on Saturn moon Enceladus is its so-called tiger stripe pattern at the geologically active South Polar Terrain (SPT), as first observed in detail by the Cassini spacecraft early 2005. It is generally assumed that the four almost parallel surface lines that constitute this pattern are faults in the icy surface overlying a confined salty water reservoir. Indeed, later Cassini observations have shown that salty water jets originate from the tiger stripes [e.g., Hansen et al., Science, 311, 1422-1425, 2006; Postberg et al., Nature, 474, 620-622, 2011]. The periodic activity of the tiger stripe faults shows a strong correlation with tidal forcing. Jets emanating from specific fault lines seem to be triggered at those places of the faults where tidal-induced stresses are largest immediately following closest orbital approach with Saturn [e.g., Hurford et al., Nature, 447, 292-294, 2007]. Thus jet activity seems to be directly induced by tidal forcing. However, this does not explain the characteristic regular pattern of the stripes themselves. Here we explore the possibility that this pattern is formed and maintained by induced, tidally and rotationally driven, fluid motions in the ocean underneath the icy surface of the tiger-stripe region. The remarkable spatial regularity of Enceladus' SPT fault lines is reminiscent of that observed at the surface of confined density-stratified fluids by the action of induced internal gravity waves. Theoretical analysis, numerical simulations and laboratory water tank experiments all indicate that wave attractors - particular limit orbits to which waves are focused in a fluid basin - naturally emerge in gravitationally (radial salt concentration or temperature differences) or rotationally stratified confined fluids as a function of forcing periodicity and fluid basin geometry [Maas et al., Nature, 338, 557-561, 1997]. We have found that ocean dynamical wave attractors induced by tidal-effective forcing

Ac-induced disruption of the doubleDs structure in tomato

NARCIS (Netherlands)

Rommens, Caius M.T.; Biezen, Erik A. van der; Ouwerkerk, Pieter B.F.; Nijkamp, H. John J.; Hille, Jacques

1991-01-01

The maize doubleDs element is stably maintained in the tomato genome. Upon the subsequent introduction of Ac into a plant containing doubleDs, disruption of the doubleDs structure and DNA rearrangements at the site of the doubleDs element were observed. No indications were obtained for excision of

Disruption?

DEFF Research Database (Denmark)

2016-01-01

This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray......This is a short video on the theme disruption and entrepreneurship. It takes the form of an interview with John Murray...

Acceleration mechanism of vertical displacement event and its amelioration in tokamak disruptions

International Nuclear Information System (INIS)

Nakamura, Yukiharu; Yoshino, Ryuji; Pomphrey, N.; Jardin, S.C.

1996-01-01

Vertical displacement events (VDEs), which are frequently observed in disruptive discharges of elongated tokamaks, are investigated using the Tokamak Simulation Code. We show that disruption events such as a sudden plasma pressure drop (β p collapse) and the subsequent plasma current quench (I p quench) can accelerate VDEs due to the adverse destabilizing effect of the resistive shell, which has previously been thought to stabilize VDEs. In a tokamak with a surrounding shell which is asymmetric with respect to the geometric midplane, the I p quench also causes an additional VDE acceleration due to the vertical imbalance of the attractive force. While the shell-geometry characterizes the VDE dynamics, the growth rate of VDEs depends strongly on the magnitude of the β p collapse, the speed of the I p quench and the n-index of the plasma equilibrium just before the disruption. An amelioration of I p quench-induced VDEs was experimentally established in the JT-60U tokamak by optimizing the vertical location of the plasma just prior to the disruption. The JT-60U vacuum vessel is shown to be suitable for preventing the β p collapse-induced VDE. (author)

Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

Science.gov (United States)

Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

2011-01-01

AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

Disrupted integration of sensory stimuli with information about the movement of the body as a mechanism explaining LSD-induced experience.

Science.gov (United States)

Juszczak, Grzegorz R

2017-03-01

LSD (lysergic acid diethylamide) is a model psychedelic drug used to study mechanism underlying the effects induced by hallucinogens. However, despite advanced knowledge about molecular mechanism responsible for the effects induced by LSD and other related substances acting at serotonergic 5-HT 2a receptors, we still do not understand how these drugs trigger specific sensory experiences. LSD-induced experience is characterised by perception of movement in the environment and by presence of various bodily sensations such as floating in space, merging into surroundings and movement out of the physical body (the out-of-body experience). It means that a large part of the experience induced by the LSD can be simplified to the illusory movement that can be attributed to the self or to external objects. The phenomenology of the LSD-induced experience has been combined with the fact that serotonergic neurons provide all major parts of the brain with information about the level of tonic motor activity, occurrence of external stimuli and the execution of orienting responses. Therefore, it has been proposed that LSD-induced stimulation of 5-HT 2a receptors disrupts the integration of the sensory stimuli with information about the movement of the body leading to perception of illusory movement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Time for a New Agenda: Organizational Development in a Changing world with much Disruption

DEFF Research Database (Denmark)

Sørensen, Henrik B.

2017-01-01

organizations neglect to support a disruptive strategy. By demonstrating the existence of another development path, this paper attempts, from a theoretical point of view, to give a new and a more nuanced perspective on organizational development in a disruptive world. This new path is supportive in a disruptive......Abstract – Traditional organizational theory tends to point out that organizational development follows a certain pattern where the structure of the company is said to become ever more bureaucratic. However, in a world where all companies and industries are faced with disruption, bureaucratic...... world. The aim of the paper is to answer the following research question: How can companies manage processes of organizational development and structures to avoid the bureaucracy and potential crises of the traditional approach in a disruptive world? This research question is important because...

Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder

Directory of Open Access Journals (Sweden)

Maria eRazzoli

2015-01-01

Full Text Available Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Methods: Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm. Conclusion: Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food

Disruption of PCNA-lamins A/C interactions by prelamin A induces DNA replication fork stalling.

Science.gov (United States)

Cobb, Andrew M; Murray, Thomas V; Warren, Derek T; Liu, Yiwen; Shanahan, Catherine M

2016-09-02

The accumulation of prelamin A is linked to disruption of cellular homeostasis, tissue degeneration and aging. Its expression is implicated in compromised genome stability and increased levels of DNA damage, but to date there is no complete explanation for how prelamin A exerts its toxic effects. As the nuclear lamina is important for DNA replication we wanted to investigate the relationship between prelamin A expression and DNA replication fork stability. In this study we report that the expression of prelamin A in U2OS cells induced both mono-ubiquitination of proliferating cell nuclear antigen (PCNA) and subsequent induction of Pol η, two hallmarks of DNA replication fork stalling. Immunofluorescence microscopy revealed that cells expressing prelamin A presented with high levels of colocalisation between PCNA and γH2AX, indicating collapse of stalled DNA replication forks into DNA double-strand breaks. Subsequent protein-protein interaction assays showed prelamin A interacted with PCNA and that its presence mitigated interactions between PCNA and the mature nuclear lamina. Thus, we propose that the cytotoxicity of prelamin A arises in part, from it actively competing against mature lamin A to bind PCNA and that this destabilises DNA replication to induce fork stalling which in turn contributes to genomic instability.

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning.

Science.gov (United States)

Galloway, Jenna L; Delgado, Irene; Ros, Maria A; Tabin, Clifford J

2009-07-16

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation. Both X-irradiation and thalidomide-induced phocomelia have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'. Indeed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support the predictions of the progress zone model.

Patterns of gravity induced aggregate migration during casting of fluid concretes

DEFF Research Database (Denmark)

Spangenberg, Jon; Roussel, N.; Hattel, Jesper Henri

2012-01-01

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in...

Directed partial correlation: inferring large-scale gene regulatory network through induced topology disruptions.

Directory of Open Access Journals (Sweden)

Yinyin Yuan

Full Text Available Inferring regulatory relationships among many genes based on their temporal variation in transcript abundance has been a popular research topic. Due to the nature of microarray experiments, classical tools for time series analysis lose power since the number of variables far exceeds the number of the samples. In this paper, we describe some of the existing multivariate inference techniques that are applicable to hundreds of variables and show the potential challenges for small-sample, large-scale data. We propose a directed partial correlation (DPC method as an efficient and effective solution to regulatory network inference using these data. Specifically for genomic data, the proposed method is designed to deal with large-scale datasets. It combines the efficiency of partial correlation for setting up network topology by testing conditional independence, and the concept of Granger causality to assess topology change with induced interruptions. The idea is that when a transcription factor is induced artificially within a gene network, the disruption of the network by the induction signifies a genes role in transcriptional regulation. The benchmarking results using GeneNetWeaver, the simulator for the DREAM challenges, provide strong evidence of the outstanding performance of the proposed DPC method. When applied to real biological data, the inferred starch metabolism network in Arabidopsis reveals many biologically meaningful network modules worthy of further investigation. These results collectively suggest DPC is a versatile tool for genomics research. The R package DPC is available for download (http://code.google.com/p/dpcnet/.

Selective wetting-induced micro-electrode patterning for flexible micro-supercapacitors.

Science.gov (United States)

Kim, Sung-Kon; Koo, Hyung-Jun; Lee, Aeri; Braun, Paul V

2014-08-13

Selective wetting-induced micro-electrode patterning is used to fabricate flexible micro-supercapacitors (mSCs). The resulting mSCs exhibit high performance, mechanical stability, stable cycle life, and hold great promise for facile integration into flexible devices requiring on-chip energy storage. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development

International Nuclear Information System (INIS)

Wang Qiang; Luo Wenjing; Zheng Wei; Liu Yiping; Xu Hui; Zheng Gang; Dai Zhongming; Zhang Wenbin; Chen Yaoming; Chen Jingyuan

2007-01-01

Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 μg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO 4 solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p < 0.05) and brain tissues by 1.5-2.0-folds (p < 0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p < 0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications

Disruption of Structural and Functional Networks in Long-Standing Multiple Sclerosis

NARCIS (Netherlands)

Tewarie, P.; Steenwijk, M.D.; Tijms, B.M.; Daams, M.; Balk, L.J.; Stam, C.J.; Uitdehaag, B.M.J.; Polman, C.H.; Geurts, J.J.G.; Barkhof, F.; Pouwels, P.J.W.; Vrenken, H.; Hillebrand, A.

2014-01-01

Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter

OPTIMIZATION OF CELL DISRUPTION IN RAPHIDOCELIS SUBCAPITATA AND CHLORELLA VULGARIS FOR BIOMARKER EVALUATION

Directory of Open Access Journals (Sweden)

Adeolu Aderemi

2015-06-01

Full Text Available Raphidocelis subcapitata and Chlorella vulgaris are bioassay microalgae with rigid cellulosic cell wall which can hinder the release of intracellular proteins often studied as toxicity biomarkers. Since cell disruption is necessary for recovering intracellular biomolecules in these organisms, this study investigated the efficiency of ultrasonication bath; ultrasonication probe; vortexer; and bead mill in disintegrating the microalgae for anti-oxidative enzyme extraction. The extent of cell disruption was evaluated and quantified using bright field microscopy. Disrupted algae appeared as ghosts. The greatest disintegration of the microalgae (83-99.6 % was achieved using bead mill with 0.42-0.6 mm glass beads while the other methods induced little or no disruption. The degree of cell disruption using bead mill increased with exposure time, beads-solution ratio and agitation speed while larger beads caused less disruption. Findings revealed that bead milling, with specific parameters optimized, is one of the most effective methods of disintegrating the robust algal cells.

The habitat disruption induces immune-suppression and oxidative stress in honey bees

Science.gov (United States)

Morimoto, Tomomi; Kojima, Yuriko; Toki, Taku; Komeda, Yayoi; Yoshiyama, Mikio; Kimura, Kiyoshi; Nirasawa, Keijiro; Kadowaki, Tatsuhiko

2011-01-01

The honey bee is a major insect used for pollination of many commercial crops worldwide. Although the use of honey bees for pollination can disrupt the habitat, the effects on their physiology have never been determined. Recently, honey bee colonies have often collapsed when introduced in greenhouses for pollination in Japan. Thus, suppressing colony collapses and maintaining the number of worker bees in the colonies is essential for successful long-term pollination in greenhouses and recycling of honey bee colonies. To understand the physiological states of honey bees used for long-term pollination in greenhouses, we characterized their gene expression profiles by microarray. We found that the greenhouse environment changes the gene expression profiles and induces immune-suppression and oxidative stress in honey bees. In fact, the increase of the number of Nosema microsporidia and protein carbonyl content was observed in honey bees during pollination in greenhouses. Thus, honey bee colonies are likely to collapse during pollination in greenhouses when heavily infested with pathogens. Degradation of honey bee habitat by changing the outside environment of the colony, during pollination services for example, imposes negative impacts on honey bees. Thus, worldwide use of honey bees for crop pollination in general could be one of reasons for the decline of managed honey bee colonies. PMID:22393496

Interfacial patterns in magnetorheological fluids: Azimuthal field-induced structures.

Science.gov (United States)

Dias, Eduardo O; Lira, Sérgio A; Miranda, José A

2015-08-01

Despite their practical and academic relevance, studies of interfacial pattern formation in confined magnetorheological (MR) fluids have been largely overlooked in the literature. In this work, we present a contribution to this soft matter research topic and investigate the emergence of interfacial instabilities when an inviscid, initially circular bubble of a Newtonian fluid is surrounded by a MR fluid in a Hele-Shaw cell apparatus. An externally applied, in-plane azimuthal magnetic field produced by a current-carrying wire induces interfacial disturbances at the two-fluid interface, and pattern-forming structures arise. Linear stability analysis, weakly nonlinear theory, and a vortex sheet approach are used to access early linear and intermediate nonlinear time regimes, as well as to determine stationary interfacial shapes at fully nonlinear stages.

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns.

Science.gov (United States)

Janno, Sven; Holi, Matti M; Tuisku, Katinka; Wahlbeck, Kristian

2008-04-18

Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders - Fourth Edition (DSM-IV).Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

Disruptions in JET

International Nuclear Information System (INIS)

Wesson, J.A.; Gill, R.D.; Hugon, M.

1989-01-01

In JET, both high density and low-q operation are limited by disruptions. The density limit disruptions are caused initially by impurity radiation. This causes a contraction of the plasma temperature profile and leads to an MHD unstable configuration. There is evidence of magnetic island formation resulting in minor disruptions. After several minor disruptions, a major disruption with a rapid energy quench occurs. This event takes place in two stages. In the first stage there is a loss of energy from the central region. In the second stage there is a more rapid drop to a very low temperature, apparently due to a dramatic increase in impurity radiation. The final current decay takes place in the resulting cold plasma. During the growth of the MHD instability the initially rotating mode is brought to rest. This mode locking is believed to be due to an electromagnetic interaction with the vacuum vessel and external magnetic field asymmetries. The low-q disruptions are remarkable for the precision with which they occur at q ψ = 2. These disruptions do not have extended precursors or minor disruptions. The instability grows and locks rapidly. The energy quench and current decay are generally similar to those of the density limit. (author). 43 refs, 35 figs, 3 tabs

Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

International Nuclear Information System (INIS)

Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

2013-01-01

Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

Energy Technology Data Exchange (ETDEWEB)

Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

2013-11-01

Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

Recent Insights in Islet Amyloid Polypeptide-Induced Membrane Disruption and Its Role in β-Cell Death in Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Lucie Khemtémourian

2008-01-01

Full Text Available The presence of fibrillar protein deposits (amyloid of human islet amyloid polypeptide (hIAPP in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing islet β-cells in type 2 diabetes mellitus (DM2. The mechanism of hIAPP-induced β-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of β-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer’s disease, Parkinson’s disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure and on the proposed mechanisms of hIAPP-induced membrane damage in relation to β-cell death in DM2.

Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins.

Science.gov (United States)

Morimoto, A; Nakamori, T; Watanabe, T; Ono, T; Murakami, N

1988-04-01

To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.

Inhibition of di(2-ethylhexyl) phthalate (DEHP)-induced endocrine disruption by co-treatment of vitamins C and E and their mechanism of action.

Science.gov (United States)

Choi, Seul Min; Lim, Duck Soo; Kim, Min Kook; Yoon, Sungpil; Kacew, Sam; Kim, Hyung Sik; Lee, Byung-Mu

2018-05-29

The endocrine disrupting actions of di(2-ethylhexyl) phthalate (DEHP) on testicular functions are postulated to involve excess free radical generation. Thus the aim of this study was to examine the ability of antioxidant vitamins C and E to prevent DEHP-induced testicular disruption in male Sprague-Dawley (SD) rats. SD male rats were administered DEHP alone or DEHP with vitamin C and/or vitamin E for 30 days. DEHP alone increased the levels of testosterone (T) and reduced estradiol (E 2 ) concentrations. Supplementation with antioxidant vitamins diminished or restored serum T levels noted in DEHP-treated rats to control values. In contrast vitamins C and E increased E 2 levels to control in rats administered DEHP. Antioxidants significantly improved the decreased testicular levels of reduced glutathione and activity of superoxide dismutase compared to DEHP-treatment alone. Co-treatment of vitamins C and E also markedly improved the reduced epididymal sperm head counts and elevated levels of malondialdehyde (MDA) or 8-hydroxydeoxyguanosine (8-OHdG) induced by DEHP treatment. These results support the concept that the adverse actions of DEHP may be related to increased free radical generation while co-treatment with vitamins C and E significantly blocked the actions of DEHP on male testicular functions.

DSTAR: A comprehensive tokamak resistive disruption model for vacuum vessel components

International Nuclear Information System (INIS)

Merrill, B.J.; Jardin, S.C.

1987-01-01

A computer code, DSTAR, has recently been developed to quantify the surface erosion and induced forces than can occur during major tokamak plasma disruptions. A disruption analysis has been performed for the TFCX fusion device. The limiters and inboard first wall were assumed to be clad with beryllium. Disruption simulations were performed with and without these structures present, to determine their electromagnetic influence. The results with structure show that the ablated wall material is transported poloidally, as well as radially, in the plasma causing the outermost regions of the plasma to cool. The plasma moves downward and deforms while maintaining contact with the lower limiter. This motion maintains the peak impurity radiant source directly above the exposed surface. For the disruption simulation without the vacuum vessel included, the plasma moves radially along the lower limiter until it contacts the inboard wall, causing ablation of this surface as well. The conclusion is drawn that disruption simulations that do not include both the thermal and electromagnetic response of the vaccum vessel will not result in an accurate prediction. (orig.)

Characterization of plasma current quench during disruptions at HL-2A

Science.gov (United States)

Zhu, Jinxia; Zhang, Yipo; Dong, Yunbo; HL-2A Team

2017-05-01

The most essential assumptions of physics for the evaluation of electromagnetic forces on the plasma-facing components due to a disruption-induced eddy current are characteristics of plasma current quenches including the current quench rate or its waveforms. The characteristics of plasma current quenches at HL-2A have been analyzed during spontaneous disruptions. Both linear decay and exponential decay are found in the disruptions with the fastest current quenches. However, there are two stages of current quench in the slow current quench case. The first stage with an exponential decay and the second stage followed by a rapid linear decay. The faster current quench rate corresponds to the faster movement of plasma displacement. The parameter regimes on the current quench time and the current quench rates have been obtained from disruption statistics at HL-2A. There exists no remarkable difference for distributions obtained between the limiter and the divertor configuration. This data from HL-2A provides basic data of the derivation of design criteria for a large-sized machine during the current decay phase of the disruptions.

Fungal innate immunity induced by bacterial microbe-associated molecular patterns (MAMPs)

DEFF Research Database (Denmark)

Ip Cho, Simon; Sundelin, Thomas; Erbs, Gitte

2016-01-01

Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal-bacterial interaction at the molecular level is still in its infancy and little is known about MAMPs and their detection by fungi. Exposin...

DISRUPTION OF CONDITIONED REWARD ASSOCIATION BY TYPICAL AND ATYPICAL ANTIPSYCHOTICS

Science.gov (United States)

Danna, C.L.; Elmer, G.I.

2013-01-01

Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100 μg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3–30 μg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward

Digital disruption ?syndromes.

Science.gov (United States)

Sullivan, Clair; Staib, Andrew

2017-05-18

The digital transformation of hospitals in Australia is occurring rapidly in order to facilitate innovation and improve efficiency. Rapid transformation can cause temporary disruption of hospital workflows and staff as processes are adapted to the new digital workflows. The aim of this paper is to outline various types of digital disruption and some strategies for effective management. A large tertiary university hospital recently underwent a rapid, successful roll-out of an integrated electronic medical record (EMR). We observed this transformation and propose several digital disruption "syndromes" to assist with understanding and management during digital transformation: digital deceleration, digital transparency, digital hypervigilance, data discordance, digital churn and post-digital 'depression'. These 'syndromes' are defined and discussed in detail. Successful management of this temporary digital disruption is important to ensure a successful transition to a digital platform. What is known about this topic? Digital disruption is defined as the changes facilitated by digital technologies that occur at a pace and magnitude that disrupt established ways of value creation, social interactions, doing business and more generally our thinking. Increasing numbers of Australian hospitals are implementing digital solutions to replace traditional paper-based systems for patient care in order to create opportunities for improved care and efficiencies. Such large scale change has the potential to create transient disruption to workflows and staff. Managing this temporary disruption effectively is an important factor in the successful implementation of an EMR. What does this paper add? A large tertiary university hospital recently underwent a successful rapid roll-out of an integrated electronic medical record (EMR) to become Australia's largest digital hospital over a 3-week period. We observed and assisted with the management of several cultural, behavioural and

Directed mutagenesis in Candida albicans: one-step gene disruption to isolate ura3 mutants

International Nuclear Information System (INIS)

Kelly, R.; Miller, S.M.; Kurtz, M.B.; Kirsch, D.R.

1987-01-01

A method for introducing specific mutations into the diploid Candida albicans by one-step gene disruption and subsequent UV-induced recombination was developed. The cloned C. albicans URA3 gene was disrupted with the C. albicans ADE2 gene, and the linearized DNA was used for transformation of two ade2 mutants, SGY-129 and A81-Pu. Both an insertional inactivation of the URA3 gene and a disruption which results in a 4.0-kilobase deletion were made. Southern hybridization analyses demonstrated that the URA3 gene was disrupted on one of the chromosomal homologs in 15 of the 18 transformants analyzed. These analyses also revealed restriction site dimorphism of EcoRI at the URA3 locus which provides a unique marker to distinguish between chromosomal homologs. This enabled us to show that either homolog could be disrupted and that disrupted transformants of SGY-129 contained more than two copies of the URA3 locus. The A81-Pu transformants heterozygous for the ura3 mutations were rendered homozygous and Ura- by UV-induced recombination. The homozygosity of a deletion mutant and an insertion mutant was confirmed by Southern hybridization. Both mutants were transformed to Ura+ with plasmids containing the URA3 gene and in addition, were resistant to 5-fluoro-orotic acid, a characteristic of Saccharomyces cerevisiae ura3 mutants as well as of orotidine-5'-phosphate decarboxylase mutants of other organisms

Extensor Mechanism Disruption after Total Knee Arthroplasty: A Case Series and Review of Literature.

Science.gov (United States)

Vaishya, Raju; Agarwal, Amit Kumar; Vijay, Vipul

2016-02-04

Extensor mechanism disruption following total knee arthroplasty (TKA) is a rare but devastating complication. These patients may require revision of the implants, but even then, it may not be possible to restore the normal function of the knee after the disruption. The patterns of extensor mechanism disruption can broadly be classified into three types: suprapatellar (quadriceps tendon rupture), transpatellar (patellar fracture), or infrapatellar (patellar tendon rupture). Infrapatellar tendon ruptures are the worst injuries, as they carry maximum morbidity and are challenging to manage. The disruption of the extensor mechanism may occur either intra-operatively or in the immediate postoperative period due to an injury. The treatment of extensor mechanism complications after TKA may include either nonsurgical management or surgical intervention in the form of primary repair or reconstruction with autogenous, allogeneic, or synthetic substitutes. We have provided an algorithm for the management of extensor mechanism disruption after TKA.

Physiologically induced color-pattern changes in butterfly wings: mechanistic and evolutionary implications.

Science.gov (United States)

Otaki, Joji M

2008-07-01

A mechanistic understanding of the butterfly wing color-pattern determination can be facilitated by experimental pattern changes. Here I review physiologically induced color-pattern changes in nymphalid butterflies and their mechanistic and evolutionary implications. A type of color-pattern change can be elicited by elemental changes in size and position throughout the wing, as suggested by the nymphalid groundplan. These changes of pattern elements are bi-directional and bi-sided dislocation toward or away from eyespot foci and in both proximal and distal sides of the foci. The peripheral elements are dislocated even in the eyespot-less compartments. Anterior spots are more severely modified, suggesting the existence of an anterior-posterior gradient. In one species, eyespots are transformed into white spots with remnant-like orange scales, and such patterns emerge even at the eyespot-less "imaginary" foci. A series of these color-pattern modifications probably reveal "snap-shots" of a dynamic morphogenic signal due to heterochronic uncoupling between the signaling and reception steps. The conventional gradient model can be revised to account for these observed color-pattern changes.

The impact of shift work induced chronic circadian disruption on IL-6 and TNF-α immune responses

Directory of Open Access Journals (Sweden)

Spallek Michael

2010-07-01

Full Text Available Abstract AIM Sleep disturbances induce proinflammatory immune responses, which might increase cardiovascular disease risk. So far the effects of acute sleep deprivation and chronic sleep illnesses on the immune system have been investigated. The particular impact of shift work induced chronic circadian disruption on specific immune responses has not been addressed so far. Methods Pittsburgh-Sleep-Quality-Index (PSQI questionnaire and blood sampling was performed by 225 shift workers and 137 daytime workers. As possible markers the proinflammatory cytokines IL-6 and TNF-α and lymphocyte cell count were investigated. A medical examination was performed and biometrical data including age, gender, height, weight, waist and hip circumference and smoking habits were collected by a structured interview. Results Shift workers had a significantly higher mean PSQI score than day workers (6.73 vs. 4.66; p Conclusion Shift work induces chronic sleep debt. Our data reveals that chronic sleep debt might not always lead to an activation of the immune system, as we did not observe differences in lymphocyte count or level of IL-6 or TNF-α serum concentration between shift workers and day workers. Therefore chronic sleep restriction might be eased by a long-term compensating immune regulation which (in healthy protects against an overstimulation of proinflammatory immune mechanisms and moderates metabolic changes, as they are known from short-term sleep deprivation or sleep related breathing disorders.

Keeping the band together: evidence for false boundary disruptive coloration in a butterfly.

Science.gov (United States)

Seymoure, B M; Aiello, A

2015-09-01

There is a recent surge of evidence supporting disruptive coloration, in which patterns break up the animal's outline through false edges or boundaries, increasing survival in animals by reducing predator detection and/or preventing recognition. Although research has demonstrated that false edges are successful for reducing predation of prey, research into the role of internal false boundaries (i.e. stripes and bands) in reducing predation remains warranted. Many animals have stripes and bands that may function disruptively. Here, we test the possible disruptive function of wing band patterning in a butterfly, Anartia fatima, using artificial paper and plasticine models in Panama. We manipulated the band so that one model type had the band shifted to the wing margin (nondisruptive treatment) and another model had a discontinuous band located on the wing margin (discontinuous edge treatment). We kept the natural wing pattern to represent the false boundary treatment. Across all treatment groups, we standardized the area of colour and used avian visual models to confirm a match between manipulated and natural wing colours. False boundary models had higher survival than either the discontinuous edge model or the nondisruptive model. There was no survival difference between the discontinuous edge model and the nondisruptive model. Our results demonstrate the importance of wing bands in reducing predation on butterflies and show that markings set in from the wing margin can reduce predation more effectively than marginal bands and discontinuous marginal patterns. This study demonstrates an adaptive benefit of having stripes and bands. © 2015 European Society For Evolutionary Biology.

Relationship Between Locked Modes and Disruptions in the DIII-D Tokamak

Science.gov (United States)

Sweeney, Ryan

This thesis is organized into three body chapters: (1) the first use of naturally rotating tearing modes to diagnose intrinsic error fields is presented with experimental results from the EXTRAP T2R reversed field pinch, (2) a large scale study of locked modes (LMs) with rotating precursors in the DIII-D tokamak is reported, and (3) an in depth study of LM induced thermal collapses on a few DIII-D discharges is presented. The amplitude of naturally rotating tearing modes (TMs) in EXTRAP T2R is modulated in the presence of a resonant field (given by the superposition of the resonant intrinsic error field, and, possibly, an applied, resonant magnetic perturbation (RMP)). By scanning the amplitude and phase of the RMP and observing the phase-dependent amplitude modulation of the resonant, naturally rotating TM, the corresponding resonant error field is diagnosed. A rotating TM can decelerate and lock in the laboratory frame, under the effect of an electromagnetic torque due to eddy currents induced in the wall. These locked modes often lead to a disruption, where energy and particles are lost from the equilibrium configuration on a timescale of a few to tens of milliseconds in the DIII-D tokamak. In fusion reactors, disruptions pose a problem for the longevity of the reactor. Thus, learning to predict and avoid them is important. A database was developed consisting of ˜ 2000 DIII-D discharges exhibiting TMs that lock. The database was used to study the evolution, the nonlinear effects on equilibria, and the disruptivity of locked and quasi-stationary modes with poloidal and toroidal mode numbers m = 2 and n = 1 at DIII-D. The analysis of 22,500 discharges shows that more than 18% of disruptions present signs of locked or quasi-stationary modes with rotating precursors. A parameter formulated by the plasma internal inductance li divided by the safety factor at 95% of the toroidal flux, q95, is found to exhibit predictive capability over whether a locked mode will

On the origin of deformation-induced rotation patterns below nanoindents

International Nuclear Information System (INIS)

Zaafarani, N.; Raabe, D.; Roters, F.; Zaefferer, S.

2008-01-01

This study is about the origin of systematic deformation-induced crystallographic orientation patterns around nanoindents (here of single crystalline copper; conical indenter) using the following approach: first, the rotation pattern is investigated in three-dimensions (3D) using a high-resolution 3D electron backscattered diffraction (EBSD) technique (EBSD tomography) which works by a serial sectioning and EBSD mapping procedure in a scanning electron microscopy-focused ion beam cross-beam set-up. Second, the problem is modeled using a crystal plasticity finite element method which is based on a dislocation density-based constitutive model. Third, the results were discussed in terms of a geometrical model which simplifies the boundary conditions during indentation in terms of a compressive state normal to the local tangent of the indent shape. This simplification helps to identify the dominant slip systems and the resulting lattice rotations, thereby allowing us to reveal the basic mechanism of the formation of the rotation patterns. The finite element simulations also predict the pile-up patterning around the indents, which can be related to the dislocation density evolution

The diagnosis of internal disc disruption with CT discography

International Nuclear Information System (INIS)

Liu Miao; Chen Xingcan; Li Xiaohong; Pan Yongqin

2008-01-01

Objective: To study the value of diagnosis for internal disc disruption (IDD)with CT discography(CTD). Methods: 42 discs of 32 patients showing no disc herniation on CT or MRI, but suffering from chronic low back pain, were undertaken CTD to work out the types of CTD with correlation between contrast medium dosages and the induction of pain. Results: CTD demonstrated 4 types of IDD which was individually correlated with the contrast dosages and induced pain; furthermore the dosages for positive and negative disc cases showed significant differece (P<0.01). Conclusions: CTD can show the direct sign of internal disc disruption, providing more information than conventional discography. (authors)

Wave form of current quench during disruptions in tokamaks

International Nuclear Information System (INIS)

Sugihara, Masayoshi; Gribov, Yuri; Shimada, Michiya; Lukash, Victor; Kawano, Yasunori; Yoshino, Ryuji; Miki, Nobuharu; Ohmori, Junji; Khayrutdinov, Rustam

2003-01-01

The time dependence of the current decay during the current quench phase of disruptions, which can significantly influence the electro-magnetic force on the in-vessel components due to the induced eddy currents, is investigated using data obtained in JT-60U experiments in order to derive a relevant physics guideline for the predictive simulations of disruptions in ITER. It is shown that an exponential decay can fit the time dependence of current quench for discharges with large quench rate (fast current quench). On the other hand, for discharges with smaller quench rate (slow current quench), a linear decay can fit the time dependence of current quench better than exponential. (author)

Oral Exposure to Atrazine Induces Oxidative Stress and Calcium Homeostasis Disruption in Spleen of Mice

Directory of Open Access Journals (Sweden)

Shuying Gao

2016-01-01

Full Text Available The widely used herbicide atrazine (ATR can cause many adverse effects including immunotoxicity, but the underlying mechanisms are not fully understood. The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice. ATR at doses of 0, 100, 200, or 400 mg/kg body weight was administered to Balb/c mice daily for 21 days by oral gavage. The studies performed 24 hr after the final exposure showed that ATR could induce the generation of reactive oxygen species in the spleen of the mice, increase the level of advanced oxidation protein product (AOPP in the host serum, and cause the depletion of reduced glutathione in the serum, each in a dose-related manner. In addition, DNA damage was observed in isolated splenocytes as evidenced by increase in DNA comet tail formation. ATR exposure also caused increases in intracellular Ca2+ within splenocytes. Moreover, ATR treatment led to increased expression of genes for some antioxidant enzymes, such as HO-1 and Gpx1, as well as increased expression of NF-κB and Ref-1 proteins in the spleen. In conclusion, it appears that oxidative stress and disruptions in calcium homeostasis might play an important role in the induction of immunotoxicity in mice by ATR.

Microcystin-LR induced reactive oxygen species mediate cytoskeletal disruption and apoptosis of hepatocytes in Cyprinus carpio L.

Directory of Open Access Journals (Sweden)

Jinlin Jiang

Full Text Available Microcystins (MCs are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR contains Leucine (L and Arginine (R in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A activities and induce excessive production of reactive oxygen species (ROS. The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L. remains largely unclear. In our present study, the hydroxyl radical (•OH was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12-48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity.

Microcystin-LR Induced Reactive Oxygen Species Mediate Cytoskeletal Disruption and Apoptosis of Hepatocytes in Cyprinus carpio L.

Science.gov (United States)

Jiang, Jinlin; Shan, Zhengjun; Xu, Weili; Wang, Xiaorong; Zhou, Junying; Kong, Deyang; Xu, Jing

2013-01-01

Microcystins (MCs) are a group of cyclic hepatotoxic peptides produced by cyanobacteria. Microcystin-LR (MC-LR) contains Leucine (L) and Arginine (R) in the variable positions, and is one of the most common and potently toxic peptides. MC-LR can inhibit protein phosphatase type 1 and type 2A (PP1 and PP2A) activities and induce excessive production of reactive oxygen species (ROS). The underlying mechanism of the inhibition of PP1 and PP2A has been extensively studied. The over-production of ROS is considered to be another main mechanism behind MC-LR toxicity; however, the detailed toxicological mechanism involved in over-production of ROS in carp (Cyprinus carpio L.) remains largely unclear. In our present study, the hydroxyl radical (•OH) was significantly induced in the liver of carp after a relatively short-term exposure to MC-LR. The elevated reactive oxygen species (ROS) production may play an important role in the disruption of microtubule structure. Pre-injection of the antioxidant N-acetyl-cysteine (NAC) provided significant protection to the cytoskeleton, however buthionine sulfoximine (BSO) exacerbated cytoskeletal destruction. In addition, the elevated ROS formation induced the expression of apoptosis-related genes, including p38, JNKa, and bcl-2. A significant increase in apoptotic cells was observed at 12 - 48 hours. Our study further supports evidence that ROS are involved in MC-LR induced damage to liver cells in carp, and indicates the need for further study of the molecular mechanisms behind MC-LR toxicity. PMID:24376844

Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production.

Directory of Open Access Journals (Sweden)

Christel Gumy

Full Text Available BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK and tyrosine-aminotransferase (TAT and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6 and TNF-alpha production in lipopolysaccharide (LPS-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin.

A Reevaluation of X-Irradiation Induced Phocomelia and Proximodistal Limb Patterning

Science.gov (United States)

Galloway, Jenna L.; Delgado, Irene; Ros, Maria A.; Tabin, Clifford J.

2009-01-01

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a dramatic increase in incidence in the early 1960’s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative1, 2. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation3-5. Both X-irradiation5 and thalidomide-induced phocomelia5, 6 have been interpreted as patterning defects in the context of the Progress Zone Model, which states that a cell’s proximodistal (PD) identity is determined by the length of time spent in a distal limb region termed the “Progress Zone” 7. Indeed, studies of X-irradiation induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the Progress Zone Model. Here, using a combination of molecular analysis and lineage tracing, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. As skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the etiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that PD patterning is unaffected following X-irradiation does not support the predictions of the Progress Zone

The ergodic divertor a way to prevent major disruptions

International Nuclear Information System (INIS)

Vallet, J.C.; Poutchy, L.; Mohamed-Benkadda, M.S.; Edery, D.; Joffrin, E.; Lecoustey, P.; Pecquet, A.L.; Samain, A.; Talvard, M.

1991-01-01

The disruptions are one of the major obstacles to present day tokamaks extrapolation to fusion reactors. We have recently proposed a piloting discharge strategy on TORE SUPRA to prevent density limit disruptions. This strategy is based on the use of the Ergodic Divertor (ED). We have observed that the ED stabilizes the m=2 n=1 tearing mode and that in deuterium discharges limited by the outboard limiter it induces a fast decrease of the plasma density. The piloting strategy is taken in three steps: 1) the approach of the density limit is detected by a threshold on the MHD activity amplitude; 2) the gas puff is switched off; 3) the ED is turned on. Then the m=2 n=1 tearing mode is stabilized the density decreases and the disruption is avoided. This strategy has already been successully tested on about 20 specific deuterium shots with 2.5< q(a)<4.5 in which the density limit is approached by ramping up the density with gas puffing. In this paper, experimental data are reported and analyzed. First, the principle of the ED and the density limit disruption phenomenology are briefly recalled. Then the ED effect on plasma density, radiated power and MHD activity are analyzed, and the piloting strategy to prevent density limit disruptions is discussed

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

Directory of Open Access Journals (Sweden)

Tuisku Katinka

2008-04-01

Full Text Available Abstract Background Neuroleptic-induced movement disorders (NIMDs have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry. Methods A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV. Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD. Results The patterns of neuroleptic-induced akathisia (NIA and pseudoakathisia (PsA were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia. Conclusion The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.

Tungstate-induced color-pattern modifications of butterfly wings are independent of stress response and ecdysteroid effect.

Science.gov (United States)

Otaki, Joji M; Ogasawara, Tsuyoshi; Yamamoto, Haruhiko

2005-06-01

Systemic injections of sodium tungstate, a protein-tyrosine phosphatase (PTPase) inhibitor, to pupae immediately after pupation have been shown to efficiently produce characteristic color-pattern modifications on the wings of many species of butterflies. Here we demonstrated that the tungstate-induced modification pattern was entirely different from other chemically-induced ones in a species of nymphalid butterfly Junonia (Precis) orithya. In this species, the systemic injections of tungstate produced characteristic expansion of black area and shrinkage of white area together with the move of parafocal elements toward the wing base. Overall, pattern boundaries became obscure. In contrast, an entirely different modification pattern, overall darkening of wings, was observed by the injections of stress-inducing chemicals, thapsigargin, ionomycin, or geldanamycin, to pupae under the rearing conditions for the adult summer form. On the ventral wings, this darkening was due to an increase of the proportion of peppered dark scales, which was reminiscent of the natural fall form of this species. Under the same rearing conditions, the injections of ecdysteroid, which is a well-known hormone being responsible for the seasonal polyphenism of nymphalid butterflies, yielded overall expansion of orange area especially around eyespots. Taken together, we conclude that the tungstate-induced modifications are clearly distinguishable from those of stress response and ecdysteroid effect. This conclusion then suggests that the putative PTPase signaling pathway that is sensitive to tungstate uniquely contributes to the wing-wide color-pattern development in butterflies.

Disruption of δ-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.

Science.gov (United States)

Chen, Hai-Jing; Xie, Wei-Yan; Hu, Fang; Zhang, Ying; Wang, Jun; Wang, Yun

2012-04-01

Our previous study identified Threonine 161 (Thr-161), located in the second intracellular loop of the δ-opioid receptor (DOR), as the only consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund's adjuvant (CFA)-induced inflammatory pain and morphine tolerance. Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain. Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. Intrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased inflammatory hypersensitivity, and inhibited DOR- but not µ-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain. Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr-161 attenuates morphine tolerance.

Preliminary investigation into aerosol mobilization resulting from fusion reactor disruptions

International Nuclear Information System (INIS)

Sharpe, J.P.; Bourham, M.A.; Gilligan, J.G.

1996-01-01

An experimental system has been developed to study disruption-induced aerosol mobilization for fusion accident analysis. The SIRENS high heat flux facility at North Carolina State University has been modified to closely simulate disruption conditions expected in tokamak reactors. A hot vapor is formed by an ablation-controlled arc and expansion cooled into a glass chamber, where particle condensation and growth occur. The particles are collected and analyzed for relevant transport properties (e.g. size distribution and shape). Particle characterization methods are discussed, and preliminary results based on simple analysis techniques are given. 2 refs., 6 figs

Linking Informant Discrepancies to Observed Variations in Young Children's Disruptive Behavior

Science.gov (United States)

De Los Reyes, Andres; Henry, David B.; Tolan, Patrick H.; Wakschlag, Lauren S.

2009-01-01

Prior work has not tested the basic theoretical notion that informant discrepancies in reports of children's behavior exist, in part, because different informants observe children's behavior in different settings. We examined patterns of observed preschool disruptive behavior across varying social contexts in the laboratory and whether they…

Disruptions in Tokamaks

International Nuclear Information System (INIS)

Bondeson, A.

1987-01-01

This paper discusses major and minor disruptions in Tokamaks. A number of models and numerical simulations of disruptions based on resistive MHD are reviewed. A discussion is given of how disruptive current profiles are correlated with the experimentally known operational limits in density and current. It is argued that the q a =2 limit is connected with stabilization of the m=2/n=1 tearing mode for a approx.< 2.7 by resistive walls and mode rotation. Experimental and theoretical observations indicate that major disruptions usually occur in at least two phases, first a 'predisruption', or loss of confinement in the region 1 < q < 2, leaving the q approx.= 1 region almost unaffected, followed by a final disruption of the central part, interpreted here as a toroidal n = 1 external kink mode. (author)

An overproduction of astellolides induced by genetic disruption of chromatin-remodeling factors in Aspergillus oryzae.

Science.gov (United States)

Shinohara, Yasutomo; Kawatani, Makoto; Futamura, Yushi; Osada, Hiroyuki; Koyama, Yasuji

2016-01-01

The filamentous fungus Aspergillus oryzae is an important industrial mold. Recent genomic analysis indicated that A. oryzae has a large number of biosynthetic genes for secondary metabolites (SMs), but many of the SMs they produce have not been identified. For better understanding of SMs production by A. oryzae, we screened a gene-disruption library of transcription factors including chromatin-remodeling factors and found two gene disruptions that show similarly altered SM production profiles. One is a homolog of Aspergillus nidulans cclA, a component of the histone 3 lysine 4 (H3K4) methyltransferase complex of proteins associated with Set1 complex, and the other, sppA, is an ortholog of Saccharomyces cerevisiae SPP1, another component of a complex of proteins associated with Set1 complex. The cclA and sppA disruptions in A. oryzae are deficient in trimethylation of H3K4. Furthermore, one of the SMs that increased in the cclA disruptant was identified as astellolide F (14-deacetyl astellolide B). These data indicate that both cclA and sppA affect production of SMs including astellolides by affecting the methylation status of H3K4 in A. oryzae.

Regeneration patterns in boreal Scots pine glades linked to cold-induced photoinhibition

NARCIS (Netherlands)

Slot, M.; Wirth, C.; Schumacher, J.; Mohren, G.M.J.; Shibistova, O.; Lloyd, J.; Ensminger, I.

2005-01-01

Summary Regeneration patterns of Pinus sylvestris L. juveniles in central Siberian glades were studied in relation to cold-induced photoinhibition. Spatial distribution of seedlings in different height classes revealed higher seedling densities beneath the canopy than beyond the canopy, and

Study of runaway electron generation process during major disruptions in JET

International Nuclear Information System (INIS)

Plyusnin, V.V.; Riccardo, V.; Alper, B.; Kiptily, V.G.; Popovichev, S.; Helander, P.; Jaspers, R.; Mlynar, J.; Luna, E. de La; Andersson, F.

2005-01-01

The analysis of a large number of JET disruptions has provided further data on the trends of the disruption induced runaway process in large tokamaks. The role of primary runaway electrons generated at the thermal quench has been examined to assess their influence on secondary avalanching, which is recognized as a main source of large runaway currents created during disruptions. The tomographic reconstruction of the soft X-ray emission during the thermal quench has made possible the observation of the magnetic flux geometry evolution and the locating of the most probable zones for generation and confinement of the primary runaway electrons. Runaway currents have been found to increase with toroidal magnetic field and pre-disruption plasma current values. The average conversion efficiency is approximately 40-45% at a wide range of plasma currents. This agrees well with results of numerical simulations, which predict similar conversion rates at an assumed post-disruption plasma electron temperature of 10 eV. The experimental trends and numerical simulations show that runaway electrons might be an issue for ITER and therefore it remains prudent to develop mitigation methods, which suppress runaway generation. (author)

Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage.

Directory of Open Access Journals (Sweden)

Yanjiang Li

Full Text Available Blood brain barrier (BBB disruption is a key mechanism of subarachnoid hemorrhage (SAH-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX or vehicle (100mg/kg for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.

Mixtures of endocrine-disrupting contaminants induce adverse developmental effects in preweaning rats

DEFF Research Database (Denmark)

Petersen, Marta Axelstad; Christiansen, Sofie; Boberg, Julie

2014-01-01

Reproductive toxicity was investigated in rats after developmental exposure to a mixture of 13 endocrine-disrupting contaminants, including pesticides, plastic and cosmetic ingredients, and paracetamol. The mixture was composed on the basis of information about high-end human exposures...

Physical and metallurgical phenomena during simulations of plasma disruptions

International Nuclear Information System (INIS)

Brossa, F.; Cambini, M.; Quataert, D.; Rigon, G.; Schiller, P.

1988-01-01

The metallographic analysis executed on austenitic stainless steel specimens subjected to simulated plasma disruptions allows us to present a complete picture of the most important phenomena. (i) The experiments show that for the calculation of melt layer and evaporation it is necessary to take considerable convection in the melt layer into account. (ii) The rapid solidification of the melt layer leads to a change in the crystalline structure and to the formation of cracks. (iii) Alloying elements with a high vapour pressure evaporate preferentially. (iv) The stresses generated during cooling induce in some case phase changes. (v) During neutron irradiation helium is formed in all first wall materials by (n, α) processes. This helium forms bubbles under disruptions. (orig.)

Cationic peptide exposure enhances pulsed-electric-field-mediated membrane disruption.

Science.gov (United States)

Kennedy, Stephen M; Aiken, Erik J; Beres, Kaytlyn A; Hahn, Adam R; Kamin, Samantha J; Hagness, Susan C; Booske, John H; Murphy, William L

2014-01-01

The use of pulsed electric fields (PEFs) to irreversibly electroporate cells is a promising approach for destroying undesirable cells. This approach may gain enhanced applicability if the intensity of the PEF required to electrically disrupt cell membranes can be reduced via exposure to a molecular deliverable. This will be particularly impactful if that reduced PEF minimally influences cells that are not exposed to the deliverable. We hypothesized that the introduction of charged molecules to the cell surfaces would create regions of enhanced transmembrane electric potential in the vicinity of each charged molecule, thereby lowering the PEF intensity required to disrupt the plasma membranes. This study will therefore examine if exposure to cationic peptides can enhance a PEF's ability to disrupt plasma membranes. We exposed leukemia cells to 40 μs PEFs in media containing varying concentrations of a cationic peptide, polyarginine. We observed the internalization of a membrane integrity indicator, propidium iodide (PI), in real time. Based on an individual cell's PI fluorescence versus time signature, we were able to determine the relative degree of membrane disruption. When using 1-2 kV/cm, exposure to >50 μg/ml of polyarginine resulted in immediate and high levels of PI uptake, indicating severe membrane disruption, whereas in the absence of peptide, cells predominantly exhibited signatures indicative of no membrane disruption. Additionally, PI entered cells through the anode-facing membrane when exposed to cationic peptide, which was theoretically expected. Exposure to cationic peptides reduced the PEF intensity required to induce rapid and irreversible membrane disruption. Critically, peptide exposure reduced the PEF intensities required to elicit irreversible membrane disruption at normally sub-electroporation intensities. We believe that these cationic peptides, when coupled with current advancements in cell targeting techniques will be useful tools in

Visual Learning Induces Changes in Resting-State fMRI Multivariate Pattern of Information.

Science.gov (United States)

Guidotti, Roberto; Del Gratta, Cosimo; Baldassarre, Antonello; Romani, Gian Luca; Corbetta, Maurizio

2015-07-08

When measured with functional magnetic resonance imaging (fMRI) in the resting state (R-fMRI), spontaneous activity is correlated between brain regions that are anatomically and functionally related. Learning and/or task performance can induce modulation of the resting synchronization between brain regions. Moreover, at the neuronal level spontaneous brain activity can replay patterns evoked by a previously presented stimulus. Here we test whether visual learning/task performance can induce a change in the patterns of coded information in R-fMRI signals consistent with a role of spontaneous activity in representing task-relevant information. Human subjects underwent R-fMRI before and after perceptual learning on a novel visual shape orientation discrimination task. Task-evoked fMRI patterns to trained versus novel stimuli were recorded after learning was completed, and before the second R-fMRI session. Using multivariate pattern analysis on task-evoked signals, we found patterns in several cortical regions, as follows: visual cortex, V3/V3A/V7; within the default mode network, precuneus, and inferior parietal lobule; and, within the dorsal attention network, intraparietal sulcus, which discriminated between trained and novel visual stimuli. The accuracy of classification was strongly correlated with behavioral performance. Next, we measured multivariate patterns in R-fMRI signals before and after learning. The frequency and similarity of resting states representing the task/visual stimuli states increased post-learning in the same cortical regions recruited by the task. These findings support a representational role of spontaneous brain activity. Copyright © 2015 the authors 0270-6474/15/359786-13$15.00/0.

Local and integral disruption forces on the tokamak wall

Science.gov (United States)

Pustovitov, V. D.; Kiramov, D. I.

2018-04-01

The disruption-induced forces on the tokamak wall are evaluated analytically within the standard large-aspect-ratio model that implies axisymmetry, circular plasma and wall, and absence of halo currents. Additionally, the ideal-wall reaction is assumed. The disruptions are modelled as rapid changes in the plasma pressure (thermal quench (TQ)) and net current (current quench (CQ)). The force distribution over the poloidal angle is found as a function of these inputs. The derived formulas allow comparison of the TQ- and CQ-produced forces calculated differently, with and without account of the poloidal current induced in the wall. The latter variant represents the inherent property of the codes treating the wall as a set of toroidal filaments. It is proved here that such a simplification leads to unacceptably large errors in the simulated forces for both TQs and CQs. It is also shown that the TQ part of the force must prevail over that due to CQ in the high-β scenarios developed for JT-60SA and ITER.

Wound Disruption Following Colorectal Operations.

Science.gov (United States)

Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

2015-12-01

Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

GRIM-19 disrupts E6/E6AP complex to rescue p53 and induce apoptosis in cervical cancers.

Directory of Open Access Journals (Sweden)

Ying Zhou

Full Text Available BACKGROUND: Our previous studies showed a down-regulation of GRIM-19 in primary human cervical cancers, and restoration of GRIM-19 induced tumor regression. The induction of tumor suppressor protein p53 ubiquitination and degradation by E6 oncoportein of high risk-HPV through forming a stable complex with E6AP is considered as a critical mechanism for cervical tumor development. The aims of this study were to determine the potential role of GRIM-19 in rescuing p53 protein and inducing cervical cancer cell apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The protein levels of GRIM-19 and p53 were detected in normal cervical tissues from 45 patients who underwent hysterectomy for reasons other than neoplasias of either the cervix or endometrium, and cervical cancer tissues from 60 patients with non-metastatic squamous epithelial carcinomas. Coimmunoprecipitation and GST pull-down assay were performed to examine the interaction of GRIM-19 with 18E6 and E6AP in vivo and in vitro respectively. The competition of 18E6 with E6AP in binding GRIM-19 by performing competition pull-down assays was designed to examine the disruption of E6/E6AP complex by GRIM-19. The augment of E6AP ubiquitination by GRIM-19 was detected in vivo and in vitro ubiquitination assay. The effects of GRIM-19-dependent p53 accumulation on cell proliferation, cell cycle, apoptosis were explored by MTT, flow cytometry and transmission electron microscopy respectively. The tumor suppression was detected by xenograft mouse model. CONCLUSION/SIGNIFICANCE: The levels of GRIM-19 and p53 were concurrently down regulated in cervical cancers. The restoration of GRIM-19 can induce ubiquitination and degradation of E6AP, and disrupt the E6/E6AP complex through the interaction of N-terminus of GRIM-19 with both E6 and E6AP, which protected p53 from degradation and promoted cell apoptosis. Tumor xenograft studies also revealed the suppression of p53 degradation in presence of GRIM-19. These data

TIE2-expressing macrophages limit the therapeutic efficacy of the vascular disrupting agent, combretastatin A4 phosphate in mice.

OpenAIRE

Welford, Abigail F.; Biziato, Daniela; Coffelt, Seth B.; Nucera, Silvia; Fisher, Matthew; Pucci, Ferdinando; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele; Tozer, Gillian M.; Lewis, Claire E.

2011-01-01

Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA...

Severe blood-brain barrier disruption and surrounding tissue injury.

Science.gov (United States)

Chen, Bo; Friedman, Beth; Cheng, Qun; Tsai, Phil; Schim, Erica; Kleinfeld, David; Lyden, Patrick D

2009-12-01

Blood-brain barrier opening during ischemia follows a biphasic time course, may be partially reversible, and allows plasma constituents to enter brain and possibly damage cells. In contrast, severe vascular disruption after ischemia is unlikely to be reversible and allows even further extravasation of potentially harmful plasma constituents. We sought to use simple fluorescent tracers to allow wide-scale visualization of severely damaged vessels and determine whether such vascular disruption colocalized with regions of severe parenchymal injury. Severe vascular disruption and ischemic injury was produced in adult Sprague Dawley rats by transient occlusion of the middle cerebral artery for 1, 2, 4, or 8 hours, followed by 30 minutes of reperfusion. Fluorescein isothiocyanate-dextran (2 MDa) was injected intravenously before occlusion. After perfusion-fixation, brain sections were processed for ultrastructure or fluorescence imaging. We identified early evidence of tissue damage with Fluoro-Jade staining of dying cells. With increasing ischemia duration, greater quantities of high molecular weight dextran-fluorescein isothiocyanate invaded and marked ischemic regions in a characteristic pattern, appearing first in the medial striatum, spreading to the lateral striatum, and finally involving cortex; maximal injury was seen in the mid-parietal areas, consistent with the known ischemic zone in this model. The regional distribution of the severe vascular disruption correlated with the distribution of 24-hour 2,3,5-triphenyltetrazolium chloride pallor (r=0.75; P<0.05) and the cell death marker Fluoro-Jade (r=0.86; P<0.05). Ultrastructural examination showed significantly increased areas of swollen astrocytic foot process and swollen mitochondria in regions of high compared to low leakage, and compared to contralateral homologous regions (ANOVA P<0.01). Dextran extravasation into the basement membrane and surrounding tissue increased significantly from 2 to 8 hours of

Circadian clock genes Per1 and Per2 regulate the response of metabolism-associated transcripts to sleep disruption.

Directory of Open Access Journals (Sweden)

Jana Husse

Full Text Available Human and animal studies demonstrate that short sleep or poor sleep quality, e.g. in night shift workers, promote the development of obesity and diabetes. Effects of sleep disruption on glucose homeostasis and liver physiology are well documented. However, changes in adipokine levels after sleep disruption suggest that adipocytes might be another important peripheral target of sleep. Circadian clocks regulate metabolic homeostasis and clock disruption can result in obesity and the metabolic syndrome. The finding that sleep and clock disruption have very similar metabolic effects prompted us to ask whether the circadian clock machinery may mediate the metabolic consequences of sleep disruption. To test this we analyzed energy homeostasis and adipocyte transcriptome regulation in a mouse model of shift work, in which we prevented mice from sleeping during the first six hours of their normal inactive phase for five consecutive days (timed sleep restriction--TSR. We compared the effects of TSR between wild-type and Per1/2 double mutant mice with the prediction that the absence of a circadian clock in Per1/2 mutants would result in a blunted metabolic response to TSR. In wild-types, TSR induces significant transcriptional reprogramming of white adipose tissue, suggestive of increased lipogenesis, together with increased secretion of the adipokine leptin and increased food intake, hallmarks of obesity and associated leptin resistance. Some of these changes persist for at least one week after the end of TSR, indicating that even short episodes of sleep disruption can induce prolonged physiological impairments. In contrast, Per1/2 deficient mice show blunted effects of TSR on food intake, leptin levels and adipose transcription. We conclude that the absence of a functional clock in Per1/2 double mutants protects these mice from TSR-induced metabolic reprogramming, suggesting a role of the circadian timing system in regulating the physiological effects

Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

KAUST Repository

Boury-Jamot, B

2015-10-27

A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

KAUST Repository

Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, Pierre J.; Boutrel, B

2015-01-01

A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.

Protein differential expression induced by endocrine disrupting compounds in a terrestrial isopod.

NARCIS (Netherlands)

Lemos, M.F.L.; Esteves, A.C.; Samyn, B.; Timperman, I.; van Beeumen, J.; Correia, A.D.; van Gestel, C.A.M.; Soares, A.M.V.M.

2010-01-01

Endocrine disrupting compounds (EDCs) have been studied due to their impact on human health and increasing awareness of their impact on wildlife species. Studies concerning the organ-specific molecular effects of EDC in invertebrates are important to understand the mechanisms of action of this class

Mindfulness-Based Parent Training: Strategies to Lessen the Grip of Automaticity in Families with Disruptive Children

Science.gov (United States)

Dumas, Jean E.

2005-01-01

Disagreements and conflicts in families with disruptive children often reflect rigid patterns of behavior that have become overlearned and automatized with repeated practice. These patterns are mindless: They are performed with little or no awareness and are highly resistant to change. This article introduces a new, mindfulness-based model of…

Disrupting Mating Behavior of Diaphorina citri (Liviidae).

Science.gov (United States)

Lujo, S; Hartman, E; Norton, K; Pregmon, E A; Rohde, B B; Mankin, R W

2016-12-01

Severe economic damage from citrus greening disease, caused by 'Candidatus Liberibacter asiaticus' bacteria, has stimulated development of methods to reduce mating and reproduction in populations of its insect vector, Diaphorina citri (Hemiptera: Liviidae). Male D. citri find mating partners by walking on host plants, intermittently producing vibrational calls that stimulate duetting replies by receptive females. The replies provide orientational feedback, assisting the search process. To test a hypothesis that D. citri mating can be disrupted using vibrational signals that compete with and/or mask female replies, courtship bioassays were conducted in citrus trees with or without interference from female reply mimics produced by a vibrating buzzer. Statistically significant reductions occurred in the rates and proportions of mating when the buzzer produced reply mimics within 0.4 s after male courtship calls compared with undisturbed controls. Observations of courtship behaviors in the two bioassays revealed activity patterns that likely contributed to the reductions. In both disruption and control tests, males reciprocated frequently between structural bifurcations and other transition points where signal amplitudes changed. Males in the disruption bioassay had to select among vibrational signals combined from the buzzer and the female at each transition point. They often turned towards the buzzer instead of the female. There was a statistically significant reduction in the proportion of males mating if they contacted the buzzer, possibly due to its higher vibration amplitude and duration in comparison with female replies. Potential applications of D. citri mating disruption technology in citrus groves are discussed. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

Endocrine Disrupting Chemicals (EDCs)

Science.gov (United States)

... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

Oral Gingival Cell Cigarette Smoke Exposure Induces Muscle Cell Metabolic Disruption

Directory of Open Access Journals (Sweden)

Andrea C. Baeder

2016-01-01

Full Text Available Cigarette smoke exposure compromises health through damaging multiple physiological systems, including disrupting metabolic function. The purpose of this study was to determine the role of oral gingiva in mediating the deleterious metabolic effects of cigarette smoke exposure on skeletal muscle metabolic function. Using an in vitro conditioned medium cell model, skeletal muscle cells were incubated with medium from gingival cells treated with normal medium or medium containing suspended cigarette smoke extract (CSE. Following incubation of muscle cells with gingival cell conditioned medium, muscle cell mitochondrial respiration and insulin signaling and action were determined as an indication of overall muscle metabolic health. Skeletal muscle cells incubated with conditioned medium of CSE-treated gingival cells had a profound reduction in mitochondrial respiration and respiratory control. Furthermore, skeletal muscle cells had a greatly reduced response in insulin-stimulated Akt phosphorylation and glycogen synthesis. Altogether, these results provide a novel perspective on the mechanism whereby cigarette smoke affects systemic metabolic function. In conclusion, we found that oral gingival cells treated with CSE create an altered milieu that is sufficient to both disrupted skeletal muscle cell mitochondrial function and insulin sensitivity.

Femtosecond self-reconfiguration of laser-induced plasma patterns in dielectrics

Science.gov (United States)

Déziel, Jean-Luc; Dubé, Louis J.; Messaddeq, Sandra H.; Messaddeq, Younès; Varin, Charles

2018-05-01

Laser-induced modification of transparent solids by intense femtosecond laser pulses allows fast integration of nanophotonic and nanofluidic devices with controlled optical properties. Experimental observations suggest that the local and dynamic nature of the interactions between light and the transient plasma plays an important role during fabrication. Current analytical models neglect these aspects and offer limited coverage of nanograting formation on dielectric surfaces. In this paper, we present a self-consistent dynamic treatment of the plasma buildup and its interaction with light within a three-dimensional electromagnetic framework. The main finding of this work is that local light-plasma interactions are responsible for the reorientation of laser-induced periodic plasma patterns with respect to the incident light polarization, when a certain energy density threshold is reached. Plasma reconfiguration occurs within a single laser pulse, on a femtosecond time scale. Moreover, we show that the reconfigured subwavelength plasma structures actually grow into the bulk of the sample, which agrees with the experimental observations of self-organized volume nanogratings. We find that mode coupling of the incident and transversely scattered light with the periodic plasma structures is sufficient to initiate the growth and self-organization of the pattern inside the medium with a characteristic half-wavelength periodicity.

Influence of ion bombardment induced patterning of exchange bias in pinned artificial ferrimagnets on the interlayer exchange coupling

Energy Technology Data Exchange (ETDEWEB)

Schmalhorst, Jan; Reiss, Guenter; Hoenik, V. [Thin Films and Nanostructures, Department of Physics, Univ. Bielefeld (Germany); Weis, Tanja; Engel, Dieter; Ehresmann, Arno [Institute of Physics and Center for Interdisciplinary Nanostructure Science and Technology, Kassel Univ. (Germany)

2007-07-01

Artificial ferrimagnets (AFi) have many applications as, e.g., pinned reference electrodes in magnetic tunnel junctions. It is known that the application of ion bombardment induced magnetic patterning with He ions on a single layer reference electrode of magnetic tunnel junctions is possible. For some applications a combination of ion bombardment induced magnetic patterning and artificial ferrimagnets as a reference electrode is desirable. The effect of ion bombardment induced magnetic patterning on pinned artificial ferrimagnets with a Ru interlayer which is frequently used in magnetic tunnel junctions as well as pinned AFis with a Cu interlayer has been tested. Special attention has been given to the question whether the antiferromagnetic interlayer exchange coupling can withstand the ion dose necessary to turn the exchange bias.

Scintigraphic detection of regional disruption of adrenergic neurons in the heart

International Nuclear Information System (INIS)

Sisson, J.C.; Lynch, J.J.; Johnson, J.; Jaques, S. Jr.; Wu, D.; Bolgos, G.; Lucchesi, B.R.; Wieland, D.M.

1988-01-01

Experiments were designed to detect regional disruptions of adrenergic neurons in the hearts of living dogs. The neuron disruption was achieved by the application of phenol to the epicardium of the left ventricle. Evidence for denervation was the reduction in endogenous norepinephrine (NE) concentrations in the myocardium beneath the region of phenol treatment and toward the apex. Radiolabeled meta-iodobenzylguanidine (MIBG) acts as an analog of NE and as such is concentrated in adrenergic nerve terminals. Following phenol application, MIBG labeled with 125 I was found, 20 hours after injection, to be distributed within myocardium in patterns comparable to those of NE. However, left stellectomy did not alter the distributions of NE or 125 I-MIBG in the myocardium and apparently did not disrupt adrenergic innervation. MIBG labeled with 123 I enabled scintigraphic images of heart neurons in the living dog 3 and 20 hours after injection; these images portrayed the regions of adrenergic neuron disruption caused by phenol treatment. Concentrations of thallium-201 depicted on scintigraphic image and of triphenyltetrazolium observed on in vitro staining demonstrated no myocardial injury. Thus, scintigraphy with 123 I-MIBG will display regional adrenergic denervations in the heart

User's manual for DSTAR MOD1: A comprehensive tokamak disruption code

International Nuclear Information System (INIS)

Merrill, B.J.; Jardin, S.J.

1986-01-01

A computer code, DSTAR, has recently been developed to quantify the surface erosion and induced forces that can occur during major tokamak plasma disruptions. The DSTAR code development effort has been accomplished by coupling a recently developed free boundary tokamak plasma transport computational model with other models developed to predict impurity transport and radiation, and the electromagnetic and thermal dynamic response of vacuum vessel components. The combined model, DSTAR, is a unique tool for predicting the consequences of tokamak disruptions. This informal report discusses the sequence of events of a resistive disruption, models developed to predict plasma transport and electromagnetic field evolution, the growth of the stochastic region of the plasma, the transport and nonequilibrium ionization/emitted radiation of the ablated vacuum vessel material, the vacuum vessel thermal and magnetic response, and user input and code output

Synchronous oscillation prior to disruption caused by kink modes in HL-2A tokamak plasmas

Science.gov (United States)

Jiang, M.; Hu, D.; Wang, X. G.; Shi, Z. B.; Xu, Y.; Chen, W.; Ding, X. T.; Zhong, W. L.; Dong, Y. B.; Ji, X. Q.; Zhang, Y. P.; Gao, J. M.; Li, J. X.; Yang, Z. C.; Li, Y. G.; Liu, Y.

2015-08-01

A class of evident MHD activities prior to major disruption has been observed during recent radiation induced disruptions of the HL-2A tokamak discharges. It can be named SOD, synchronous oscillations prior to disruption, characterized by synchronous oscillation of electron cyclotron emission (ECE), core soft x-ray, Mirnov coil, and {{D}α} radiation signals at the divertor plate. The SOD activity is mostly observed in a parametric regime where the poloidal beta is low enough before disruption, typically corresponding to those radiation-induced disruptions. It has been found that the m/n = 2/1 mode is dominant during the SODs, and consequently it is the drop of the mode frequency and the final mode locking that lead to thermal quench. The mode frequency before the mode locking corresponds to the toroidal rotation frequency of the edge plasma. It is also found that during SODs, the location of the q = 2 surface is moving outward, and most of the plasma current is enclosed within the surface. This demonstrates that the current channel lies inside the rational surface during SOD, and thus the resistive kink mode is unstable. Further analysis of the electron temperature perturbation structure shows that the plasma is indeed dominated by the resistive kink mode, with kink-like perturbation in the core plasma region. It suggests that it is the nonlinear growth of the m/n = 2/1 resistive kink mode and its higher order harmonics, rather than the spontaneous overlapping of multiple neighboring islands, that ultimately triggered the disruption.

Cre/lox-based multiple markerless gene disruption in the genome of the extreme thermophile Thermus thermophilus.

Science.gov (United States)

Togawa, Yoichiro; Nunoshiba, Tatsuo; Hiratsu, Keiichiro

2018-02-01

Markerless gene-disruption technology is particularly useful for effective genetic analyses of Thermus thermophilus (T. thermophilus), which have a limited number of selectable markers. In an attempt to develop a novel system for the markerless disruption of genes in T. thermophilus, we applied a Cre/lox system to construct a triple gene disruptant. To achieve this, we constructed two genetic tools, a loxP-htk-loxP cassette and cre-expressing plasmid, pSH-Cre, for gene disruption and removal of the selectable marker by Cre-mediated recombination. We found that the Cre/lox system was compatible with the proliferation of the T. thermophilus HB27 strain at the lowest growth temperature (50 °C), and thus succeeded in establishing a triple gene disruptant, the (∆TTC1454::loxP, ∆TTC1535KpnI::loxP, ∆TTC1576::loxP) strain, without leaving behind a selectable marker. During the process of the sequential disruption of multiple genes, we observed the undesired deletion and inversion of the chromosomal region between multiple loxP sites that were induced by Cre-mediated recombination. Therefore, we examined the effects of a lox66-htk-lox71 cassette by exploiting the mutant lox sites, lox66 and lox71, instead of native loxP sites. We successfully constructed a (∆TTC1535::lox72, ∆TTC1537::lox72) double gene disruptant without inducing the undesired deletion of the 0.7-kbp region between the two directly oriented lox72 sites created by the Cre-mediated recombination of the lox66-htk-lox71 cassette. This is the first demonstration of a Cre/lox system being applicable to extreme thermophiles in a genetic manipulation. Our results indicate that this system is a powerful tool for multiple markerless gene disruption in T. thermophilus.

BINARY DISRUPTION BY MASSIVE BLACK HOLES: HYPERVELOCITY STARS, S STARS, AND TIDAL DISRUPTION EVENTS

Energy Technology Data Exchange (ETDEWEB)

Bromley, Benjamin C. [Department of Physics and Astronomy, University of Utah, 115 S 1400 E, Rm 201, Salt Lake City, UT 84112 (United States); Kenyon, Scott J.; Geller, Margaret J.; Brown, Warren R., E-mail: bromley@physics.utah.edu, E-mail: skenyon@cfa.harvard.edu, E-mail: mgeller@cfa.harvard.edu, E-mail: wbrown@cfa.harvard.edu [Smithsonian Astrophysical Observatory, 60 Garden Street, Cambridge, MA 02138 (United States)

2012-04-20

We examine whether disrupted binary stars can fuel black hole growth. In this mechanism, tidal disruption produces a single hypervelocity star (HVS) ejected at high velocity and a former companion star bound to the black hole. After a cluster of bound stars forms, orbital diffusion allows the black hole to accrete stars by tidal disruption at a rate comparable to the capture rate. In the Milky Way, HVSs and the S star cluster imply similar rates of 10{sup -5} to 10{sup -3} yr{sup -1} for binary disruption. These rates are consistent with estimates for the tidal disruption rate in nearby galaxies and imply significant black hole growth from disrupted binaries on 10 Gyr timescales.

Mechanical algal disruption for efficient biodiesel extraction

Science.gov (United States)

Krehbiel, Joel David

Biodiesel from algae provides several benefits over current biodiesel feedstocks, but the energy requirements of processing algae into a useable fuel are currently so high as to be prohibitive. One route to improving this is via disruption of the cells prior to lipid extraction, which can significantly increase energy recovery. Unfortunately, several obvious disruption techniques require more energy than can be gained. This dissertation examines the use of microbubbles to improve mechanical disruption of algal cells using experimental, theoretical, and computational methods. New laboratory experiments show that effective ultrasonic disruption of algae is achieved by adding microbubbles to an algal solution. The configuration studied flows the solution through a tube and insonifies a small section with a high-pressure ultrasound wave. Previous biomedical research has shown effective cell membrane damage on animal cells with similar methods, but the present research is the first to extend such study to algal cells. Results indicate that disruption increases with peak negative pressure between 1.90 and 3.07 MPa and with microbubble concentration up to 12.5 x 107 bubbles/ml. Energy estimates of this process suggest that it requires only one-fourth the currently most-efficient laboratory-scale disruption process. Estimates of the radius near each bubble that causes disruption (i.e. the disruption radius) suggest that it increases with peak negative pressure and is near 9--20 microm for all cases tested. It is anticipated that these procedures can be designed for better efficiency and efficacy, which will be facilitated by identifying the root mechanisms of the bubble-induced disruption. We therefore examine whether bubble expansion alone creates sufficient cell deformation for cell rupture. The spherically-symmetric Marmottant model for bubble dynamics allows estimation of the flow regime under experimental conditions. Bubble expansion is modeled as a point source of

Axisymmetric disruption dynamics including current profile changes in the ASDEX-Upgrade tokamak

International Nuclear Information System (INIS)

Nakamura, Y.; Pautasso, G.; Gruber, O.; Jardin, S.C.

2002-01-01

Axisymmetric MHD simulations have revealed a new driving mechanism that governs the vertical displacement event (VDE) dynamics in tokamak disruptions. A rapid flattening of the plasma current profile during the disruption plays a substantial role in dragging a single null-diverted plasma vertically towards the divertor. As a consequence, the occurrence of downward-going VDEs predominates over the upward-going ones in bottom-diverted discharges. This dragging effect, due to an abrupt change in the current profile, is absent in up-down symmetric limiter discharges. These simulation results are consistent with experiments in ASDEX-Upgrade. Together with the attractive force that arises from passive shell currents induced by the plasma current quench, the dragging effect explains many details of the VDE dynamics over the whole period of the disruptive termination. (author)

Bisphenol S disrupts estradiol-induced nongenomic signaling in a rat pituitary cell line: effects on cell functions.

Science.gov (United States)

Viñas, René; Watson, Cheryl S

2013-03-01

Bisphenol A (BPA) is a well-known endocrine disruptor that imperfectly mimics the effects of physiologic estrogens via membrane-bound estrogen receptors (mERα, mERβ, and GPER/GPR30), thereby initiating nongenomic signaling. Bisphenol S (BPS) is an alternative to BPA in plastic consumer products and thermal paper. To characterize the nongenomic activities of BPS, we examined signaling pathways it evoked in GH3/B6/F10 rat pituitary cells alone and together with the physiologic estrogen estradiol (E2). Extracellular signal-regulated kinase (ERK)- and c-Jun-N-terminal kinase (JNK)-specific phosphorylations were examined for their correlation to three functional responses: proliferation, caspase activation, and prolactin (PRL) release. We detected ERK and JNK phosphorylations by fixed-cell immunoassays, identified the predominant mER initiating the signaling with selective inhibitors, estimated cell numbers by crystal violet assays, measured caspase activity by cleavage of fluorescent caspase substrates, and measured PRL release by radioimmunoassay. BPS phosphoactivated ERK within 2.5 min in a nonmonotonic dose-dependent manner (10-15 to 10-7 M). When combined with 10-9 M E2, the physiologic estrogen's ERK response was attenuated. BPS could not activate JNK, but it greatly enhanced E2-induced JNK activity. BPS induced cell proliferation at low concentrations (femtomolar to nanomolar), similar to E2. Combinations of both estrogens reduced cell numbers below those of the vehicle control and also activated caspases. Earlier activation of caspase 8 versus caspase 9 demonstrated that BPS initiates apoptosis via the extrinsic pathway, consistent with activation via a membrane receptor. BPS also inhibited rapid (≤ 1 min) E2-induced PRL release. BPS, once considered a safe substitute for BPA, disrupts membrane-initiated E2-induced cell signaling, leading to altered cell proliferation, cell death, and PRL release.

Statistical analysis of JET disruptions

International Nuclear Information System (INIS)

Tanga, A.; Johnson, M.F.

1991-07-01

In the operation of JET and of any tokamak many discharges are terminated by a major disruption. The disruptive termination of a discharge is usually an unwanted event which may cause damage to the structure of the vessel. In a reactor disruptions are potentially a very serious problem, hence the importance of studying them and devising methods to avoid disruptions. Statistical information has been collected about the disruptions which have occurred at JET over a long span of operations. The analysis is focused on the operational aspects of the disruptions rather than on the underlining physics. (Author)

Disruptions in DIII-D

International Nuclear Information System (INIS)

Reiman, A.; Taylor, P.; Kellman, A.; LaHaye, R.

1996-01-01

We report on the results of a statistical analysis of the DIII-D disruption data base, and on an examination of a selected subset of the shots to determine the likely causes of disruptions. The statistical analysis focuses on the dependence of the disruption rate on key dimensionless parameters. We find that the disruption frequency is high at modest values of the parameters, and that it can be relatively low at operational limits. For example, the disruption frequency in an ITER relevant regime (β N /l i ∼ 2, 3 G > 0.6, where n G is the Greenwald limit) is approximately 23%. For this range of q, the disruption frequency rises only modestly to about 35% at the β limit, consistent with previous observations of a soft β limit for this q regime. For the range 6 95 G G < .9) in all q regimes we have studied. The location of the minimum moves to higher density with increasing q

Disruption model

International Nuclear Information System (INIS)

Murray, J.G.; Bronner, G.

1982-07-01

Calculations of disruption time and energy dissipation have been obtained by simulating the plasma as an electrical conducting loop that varies in resistivity, current density, major radius. The calculations provide results which are in good agreement with experimental observations. It is believed that this approach allows engineering designs for disruptions to be completed in large tokamaks such as INTOR or FED

Examining the Associations Among Home-School Dissonance, Amotivation, and Classroom Disruptive Behavior for Urban High School Students.

Science.gov (United States)

Brown-Wright, Lynda; Tyler, Kenneth M; Graves, Scott L; Thomas, Deneia; Stevens-Watkins, Danelle; Mulder, Shambra

2013-01-01

The current study examined the association among home-school dissonance, amotivation, and classroom disruptive behavior among 309 high school juniors and seniors at two urban high schools in the Southern region of the country. Students completed two subscales of the Patterns of Learning Activities Scales (PALS) and one subscale of the Academic Motivation Scale (AMS). ANCOVA analyses revealed significant differences in classroom disruptive behaviors for the gender independent variable. Controlling for gender in the multiple hierarchical regression analyses, it was revealed that home-school dissonance significantly predicted both amotivation and classroom disruptive behavior. In addition, a Sobel mediation analysis showed that amotivation was a significant mediator of the association between home-school dissonance and classroom disruptive behavior. Findings and limitations are discussed.

Examining the Associations Among Home–School Dissonance, Amotivation, and Classroom Disruptive Behavior for Urban High School Students

Science.gov (United States)

Brown-Wright, Lynda; Tyler, Kenneth M.; Graves, Scott L.; Thomas, Deneia; Stevens-Watkins, Danelle; Mulder, Shambra

2015-01-01

The current study examined the association among home–school dissonance, amotivation, and classroom disruptive behavior among 309 high school juniors and seniors at two urban high schools in the Southern region of the country. Students completed two subscales of the Patterns of Learning Activities Scales (PALS) and one subscale of the Academic Motivation Scale (AMS). ANCOVA analyses revealed significant differences in classroom disruptive behaviors for the gender independent variable. Controlling for gender in the multiple hierarchical regression analyses, it was revealed that home–school dissonance significantly predicted both amotivation and classroom disruptive behavior. In addition, a Sobel mediation analysis showed that amotivation was a significant mediator of the association between home–school dissonance and classroom disruptive behavior. Findings and limitations are discussed. PMID:27081213

Internal disruption in tokamaks

International Nuclear Information System (INIS)

Kuvshinov, B.N.; Savrukhin, P.V.

1990-01-01

A review of results of experimental and theoretical investigations of internal disruption in tokamaks is given. Specific features of various types of saw-tooth oscillations are described and their classification is performed. Theoretical models of the process of development of internal disruption instability are discussed. Effect of internal disruption on parameters of plasma, confined in tokamak, is considered. Scalings of period and amplitude of saw-tooth oscillations, as well as version radius are presented. Different methods for stabilizing instability of internal disruption are described

Internal disruptions in tokamaks

International Nuclear Information System (INIS)

Kuvshinov, B.N.; Savrukhin, P.V.

1990-01-01

Experimental and theoretical studies of the phenomenon of internal disruptions in tokamaks are reviewed. A classification scheme is introduced and the features of different types of sawtooth oscillations are described. A theoretical model for the development of the internal disruption instability is discussed. The effect of internal disruptions on the parameters of plasma confined in tokamaks is discussed. Scaling laws for the period and amplitude of sawtooth oscillations, as well as for the inversion radius, are presented. Different methods of stabilizing the internal disruption instability are described

Il camouflage nel campo allargato. Variazioni su Disruptive Pattern Material e Dazzle Painting nella cultura visiva contemporanea

Directory of Open Access Journals (Sweden)

Maite Méndez Baiges

2016-11-01

Full Text Available The First World War was the scenario that led to the invention and systematic use of military camouflage techniques. Between them, the two fundamental modes of static or pictorial camouflage: mimetic, known as Disruptive Pattern Material, and the naval, called Dazzle Painting. Avantgarde artists contributed to their birth. Immediately, there was the transfer of these techniques to the civilian sphere, revealing that its essentially practical essence did not prevent the exploitation of its aesthetic potential by contemporary visual culture. Throughout the twentieth and twenty-first centuries the fields of art, architecture and design continue importing and exploiting the strategies of these two types of military camouflage. This article analyzes the artistic potential of static military camouflage devised during World War I and its impact on the setting of an expanded notion of camouflage. If the camouflage was in its origins and early history a form of disclosure of modern art on a global scale, the use of DPM and Dazzle by contemporary artists, is a form of dissemination of military camouflage to civil level. We explore a double investment produced by military camouflage: providing avantgarde art with a practical sense, and providing camouflage with an aesthetic sense

Hepatitis C Virus and Disrupted Interferon Signaling Promote Lymphoproliferation via Type II CD95 and Interleukins

Science.gov (United States)

MACHIDA, KEIGO; TSUKIYAMA-KOHARA, KYOKO; SEKIGUCH, SATOSHI; SEIKE, EIJI; TÓNE, SHIGENOBU; HAYASHI, YUKIKO; TOBITA, YOSHIMI; KASAMA, YURI; SHIMIZU, MASUMI; TAKAHASHI, HIDEMI; TAYA, CHYOJI; YONEKAWA, HIROMICHI; TANAKA, NOBUYUKI; KOHARA, MICHINORI

2014-01-01

BACKGROUND & AIMS The molecular mechanisms of lymphoproliferation associated with the disruption of interferon (IFN) signaling and chronic hepatitis C virus (HCV) infection are poorly understood. Lymphomas are extrahepatic manifestations of HCV infection; we sought to clarify the molecular mechanisms of these processes. METHODS We established interferon regulatory factor-1– null (irf-1−/−) mice with inducible and persistent expression of HCV structural proteins (irf-1/CN2 mice). All the mice (n = 900) were observed for at least 600 days after Cre/loxP switching. Histologic analyses, as well as analyses of lymphoproliferation, sensitivity to Fas-induced apoptosis, colony formation, and cytokine production, were performed. Proteins associated with these processes were also assessed. RESULTS Irf-1/CN2 mice had extremely high incidences of lymphomas and lymphoproliferative disorders and displayed increased mortality. Disruption of irf-1 reduced the sensitivity to Fas-induced apoptosis and decreased the levels of caspases-3/7 and caspase-9 messenger RNA species and enzymatic activities. Furthermore, the irf-1/CN2 mice showed decreased activation of caspases-3/7 and caspase-9 and increased levels of interleukin (IL)-2, IL-10, and Bcl-2, as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes. IL-2 and IL-10 were induced by the HCV core protein in splenocytes. CONCLUSIONS Disruption of IFN signaling resulted in development of lymphoma, indicating that differential signaling occurs in lymphocytes compared with liver. This mouse model, in which HCV expression and disruption of IFN signaling synergize to promote lymphoproliferation, will be an important tool for the development of therapeutic agents that target the lymphoproliferative pathway. PMID:19362089

White matter tract network disruption explains reduced conscientiousness in multiple sclerosis.

Science.gov (United States)

Fuchs, Tom A; Dwyer, Michael G; Kuceyeski, Amy; Choudhery, Sanjeevani; Carolus, Keith; Li, Xian; Mallory, Matthew; Weinstock-Guttman, Bianca; Jakimovski, Dejan; Ramasamy, Deepa; Zivadinov, Robert; Benedict, Ralph H B

2018-05-08

Quantifying white matter (WM) tract disruption in people with multiple sclerosis (PwMS) provides a novel means for investigating the relationship between defective network connectivity and clinical markers. PwMS exhibit perturbations in personality, where decreased Conscientiousness is particularly prominent. This trait deficit influences disease trajectory and functional outcomes such as work capacity. We aimed to identify patterns of WM tract disruption related to decreased Conscientiousness in PwMS. Personality assessment and brain MRI were obtained in 133 PwMS and 49 age- and sex-matched healthy controls (HC). Lesion maps were applied to determine the severity of WM tract disruption between pairs of gray matter regions. Next, the Network-Based-Statistics tool was applied to identify structural networks whose disruption negatively correlates with Conscientiousness. Finally, to determine whether these networks explain unique variance above conventional MRI measures and cognition, regression models were applied controlling for age, sex, brain volume, T2-lesion volume, and cognition. Relative to HCs, PwMS exhibited lower Conscientiousness and slowed cognitive processing speed (p = .025, p = .006). Lower Conscientiousness in PwMS was significantly associated with WM tract disruption between frontal, frontal-parietal, and frontal-cingulate pathways in the left (p = .02) and right (p = .01) hemisphere. The mean disruption of these pathways explained unique additive variance in Conscientiousness, after accounting for conventional MRI markers of pathology and cognition (ΔR 2  = .049, p = .029). Damage to WM tracts between frontal, frontal-parietal, and frontal-cingulate cortical regions is significantly correlated with reduced Conscientiousness in PwMS. Tract disruption within these networks explains decreased Conscientiousness observed in PwMS as compared with HCs. © 2018 Wiley Periodicals, Inc.

Viewgraphs presented at the ASDEX/DOE workshop on disruptions in divertor tokamaks

Energy Technology Data Exchange (ETDEWEB)

Granetz, R.; Gruber, O.; Zohm, H. [and others

1994-09-01

The emphasis of this year`s ASDEX/DOE workshop was on disruptions in diverted tokamaks. The meeting was held here at MIT on 14--15 March. It is particularly appropriate that MIT hosted the workshop this year, since Alcator C-Mod had just recently completed its very first run campaign, and disruptions are one of the key areas of research in our program. There were a total of 14 speakers, with participants from IPP (Garching), CRPP (Lausanne), Culham, General Atomics, PPPL, Sandia, ORNL, the ITER JCT, and MIT. The subjects addressed included statistical analysis of disruption probabilities in ASDEX, modelling of the vertical axisymmetric plasma motion in DIII-D, impact of disruptions on the design of the ITER divertors, modelling of runaway electrons, and TSC calculations of disruption-induced currents and forces in TPX, etc. One item of particular interest to us was the experimental correlation of halo current magnitude with plasma current on ASDEX-Upgrade. The data indicates at least a linear, and possibly even a quadractic dependence. This has important implications for Alcator C-Mod, since it would predict halo currents of order 1 MA or more at full performance. At the conclusion of the talks, an informal discussion of disruption databases was held, primarily for the purpose of helping us develop a useful one for C-Mod.

Viewgraphs presented at the ASDEX/DOE workshop on disruptions in divertor tokamaks

International Nuclear Information System (INIS)

Granetz, R.; Gruber, O.; Zohm, H.

1994-01-01

The emphasis of this year's ASDEX/DOE workshop was on disruptions in diverted tokamaks. The meeting was held here at MIT on 14--15 March. It is particularly appropriate that MIT hosted the workshop this year, since Alcator C-Mod had just recently completed its very first run campaign, and disruptions are one of the key areas of research in our program. There were a total of 14 speakers, with participants from IPP (Garching), CRPP (Lausanne), Culham, General Atomics, PPPL, Sandia, ORNL, the ITER JCT, and MIT. The subjects addressed included statistical analysis of disruption probabilities in ASDEX, modelling of the vertical axisymmetric plasma motion in DIII-D, impact of disruptions on the design of the ITER divertors, modelling of runaway electrons, and TSC calculations of disruption-induced currents and forces in TPX, etc. One item of particular interest to us was the experimental correlation of halo current magnitude with plasma current on ASDEX-Upgrade. The data indicates at least a linear, and possibly even a quadractic dependence. This has important implications for Alcator C-Mod, since it would predict halo currents of order 1 MA or more at full performance. At the conclusion of the talks, an informal discussion of disruption databases was held, primarily for the purpose of helping us develop a useful one for C-Mod

Disruption of HPV16-E7 by CRISPR/Cas System Induces Apoptosis and Growth Inhibition in HPV16 Positive Human Cervical Cancer Cells

Directory of Open Access Journals (Sweden)

Zheng Hu

2014-01-01

Full Text Available High-risk human papillomavirus (HR-HPV has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR- associated protein system (CRISPR/Cas system, a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer.

Examining the Associations Among Home–School Dissonance, Amotivation, and Classroom Disruptive Behavior for Urban High School Students

OpenAIRE

Brown-Wright, Lynda; Tyler, Kenneth M.; Graves, Scott L.; Thomas, Deneia; Stevens-Watkins, Danelle; Mulder, Shambra

2011-01-01

The current study examined the association among home–school dissonance, amotivation, and classroom disruptive behavior among 309 high school juniors and seniors at two urban high schools in the Southern region of the country. Students completed two subscales of the Patterns of Learning Activities Scales (PALS) and one subscale of the Academic Motivation Scale (AMS). ANCOVA analyses revealed significant differences in classroom disruptive behaviors for the gender independent variable. Control...

Spatial pattern formation induced by Gaussian white noise.

Science.gov (United States)

Scarsoglio, Stefania; Laio, Francesco; D'Odorico, Paolo; Ridolfi, Luca

2011-02-01

The ability of Gaussian noise to induce ordered states in dynamical systems is here presented in an overview of the main stochastic mechanisms able to generate spatial patterns. These mechanisms involve: (i) a deterministic local dynamics term, accounting for the local rate of variation of the field variable, (ii) a noise component (additive or multiplicative) accounting for the unavoidable environmental disturbances, and (iii) a linear spatial coupling component, which provides spatial coherence and takes into account diffusion mechanisms. We investigate these dynamics using analytical tools, such as mean-field theory, linear stability analysis and structure function analysis, and use numerical simulations to confirm these analytical results. Copyright © 2010 Elsevier Inc. All rights reserved.

Strain-typical patterns of pregnancy-induced nestbuilding in mice: maternal and experiential influences.

Science.gov (United States)

Broida, J; Svare, B

1982-07-01

Pregnant C57BL/6J mice incorporate less material into maternal nests and build fewer fully enclosed nests than do pregnant DBA/2J mice. These strain differences are not ameliorated by additional reproductive experience since multiparous animals also exhibit a similar pattern. Reciprocally-crossed hybrid females exhibit DBA-like levels of pregnancy-induced nestbuilding and cross-fostered C57BL and DBA females retain the phenotype of their strain. Experiential and maternal environmental factors apparently are not responsible for strain differences in pregnancy-induced nestbuilding. Differences in ovarian function and/or central neural tissue sensitivity to ovarian hormones may modulate strain differences in pregnancy-induced nestbuilding.

Mixtures of xenoestrogens disrupt estradiol-induced non-genomic signaling and downstream functions in pituitary cells.

Science.gov (United States)

Viñas, René; Watson, Cheryl S

2013-03-26

possible apoptotic response. Extrinsic caspase 8 activity was suppressed by estradiol, elevated by bisphenol S, and unaffected by mixtures. Intrinsic caspase 9 activity was inhibited by estradiol, and by xenoestrogen combinations (at 10-14 and 10-8 M). Mixtures of xenoestrogens impeded the estradiol-induced release of prolactin. In mixtures expected to be found in contaminated environments, xenoestrogens can have dramatic disrupting effects on hormonal mechanisms of cell regulation and their downstream functional responses, altering cellular responses to physiologic estrogens.

Patterns of gravity induced aggregate migration during casting of fluid concretes

Energy Technology Data Exchange (ETDEWEB)

Spangenberg, J. [Department of Mechanical Engineering, Technical University of Denmark (DTU) (Denmark); Roussel, N., E-mail: Nicolas.roussel@lcpc.fr [Universite Paris Est, Laboratoire Central des Ponts et Chaussees (LCPC) (France); Hattel, J.H. [Department of Mechanical Engineering, Technical University of Denmark (DTU) (Denmark); Sarmiento, E.V.; Zirgulis, G. [Department of Structural Engineering, Norwegian University of Science and Technology (NTNU) (Norway); Geiker, M.R. [Department of Structural Engineering, Norwegian University of Science and Technology (NTNU) (Norway); Department of Civil Engineering, Technical University of Denmark (DTU) (Denmark)

2012-12-15

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration.

Patterns of gravity induced aggregate migration during casting of fluid concretes

International Nuclear Information System (INIS)

Spangenberg, J.; Roussel, N.; Hattel, J.H.; Sarmiento, E.V.; Zirgulis, G.; Geiker, M.R.

2012-01-01

In this paper, aggregate migration patterns during fluid concrete castings are studied through experiments, dimensionless approach and numerical modeling. The experimental results obtained on two beams show that gravity induced migration is primarily affecting the coarsest aggregates resulting in a decrease of coarse aggregates volume fraction with the horizontal distance from the pouring point and in a puzzling vertical multi-layer structure. The origin of this multi layer structure is discussed and analyzed with the help of numerical simulations of free surface flow. Our results suggest that it finds its origin in the non Newtonian nature of fresh concrete and that increasing casting rate shall decrease the magnitude of gravity induced particle migration.

Symposium on disruptive instabilities at Garching

International Nuclear Information System (INIS)

Lackner, K.

1979-01-01

The phenomenon of disruptive instabilities was investigated with a special care at the IPP at Garching. After lectures and panel sessions it appears suitable, to subdivide the disruptive phenomena into four classes: 1. The internal disruption (the socalled saw-tooth oscillators). 2. the socalled reconnection disruptions. 3. The large disruptions. 4. The small disruptions. The four appearance forms of the phenomena are briefly explained. (GG) [de

Statistical analysis of disruptions in JET

International Nuclear Information System (INIS)

De Vries, P.C.; Johnson, M.F.; Segui, I.

2009-01-01

The disruption rate (the percentage of discharges that disrupt) in JET was found to drop steadily over the years. Recent campaigns (2005-2007) show a yearly averaged disruption rate of only 6% while from 1991 to 1995 this was often higher than 20%. Besides the disruption rate, the so-called disruptivity, or the likelihood of a disruption depending on the plasma parameters, has been determined. The disruptivity of plasmas was found to be significantly higher close to the three main operational boundaries for tokamaks; the low-q, high density and β-limit. The frequency at which JET operated close to the density-limit increased six fold over the last decade; however, only a small reduction in disruptivity was found. Similarly the disruptivity close to the low-q and β-limit was found to be unchanged. The most significant reduction in disruptivity was found far from the operational boundaries, leading to the conclusion that the improved disruption rate is due to a better technical capability of operating JET, instead of safer operations close to the physics limits. The statistics showed that a simple protection system was able to mitigate the forces of a large fraction of disruptions, although it has proved to be at present more difficult to ameliorate the heat flux.

Improvements in disruption prediction at ASDEX Upgrade

Energy Technology Data Exchange (ETDEWEB)

Aledda, R., E-mail: raffaele.aledda@diee.unica.it; Cannas, B., E-mail: cannas@diee.unica.it; Fanni, A., E-mail: fanni@diee.unica.it; Pau, A., E-mail: alessandro.pau@diee.unica.it; Sias, G., E-mail: giuliana.sias@diee.unica.it

2015-10-15

Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

Improvements in disruption prediction at ASDEX Upgrade

International Nuclear Information System (INIS)

Aledda, R.; Cannas, B.; Fanni, A.; Pau, A.; Sias, G.

2015-01-01

Highlights: • A disruption prediction system for AUG, based on a logistic model, is designed. • The length of the disruptive phase is set for each disruption in the training set. • The model is tested on dataset different from that used during the training phase. • The generalization capability and the aging of the model have been tested. • The predictor performance is compared with the locked mode detector. - Abstract: In large-scale tokamaks disruptions have the potential to create serious damage to the facility. Hence disruptions must be avoided, but, when a disruption is unavoidable, minimizing its severity is mandatory. A reliable detection of a disruptive event is required to trigger proper mitigation actions. To this purpose machine learning methods have been widely studied to design disruption prediction systems at ASDEX Upgrade. The training phase of the proposed approaches is based on the availability of disrupted and non-disrupted discharges. In literature disruptive configurations were assumed appearing into the last 45 ms of each disruption. Even if the achieved results in terms of correct predictions were good, it has to be highlighted that the choice of such a fixed temporal window might have limited the prediction performance. In fact, it generates confusing information in cases of disruptions with disruptive phase different from 45 ms. The assessment of a specific disruptive phase for each disruptive discharge represents a relevant issue in understanding the disruptive events. In this paper, the Mahalanobis distance is applied to define a specific disruptive phase for each disruption, and a logistic regressor has been trained as disruption predictor. The results show that enhancements on the achieved performance on disruption prediction are possible by defining a specific disruptive phase for each disruption.

Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGFβ1-induced macrophages

International Nuclear Information System (INIS)

Machado, Camila Maria Longo; Andrade, Luciana Nogueira Sousa; Teixeira, Verônica Rodrigues; Costa, Fabrício Falconi; Melo, Camila Morais; Santos, Sofia Nascimento dos; Nonogaki, Suely; Liu, Fu-Tong; Bernardes, Emerson Soares; Camargo, Anamaria Aranha; Chammas, Roger

2014-01-01

In order to study the role of galectin-3 in tumor angiogenesis associated with tumor-associated macrophages (TAM) and tumor parenchyma, the galectin-3 expression was reconstituted in Tm1 melanoma cell line that lacks this protein. Galectin-3-expressing cells (Tm1G3) and mock-vector transfected cells (Tm1N3) were injected into wild-type (WT) and galectin-3 knockout (KO) C57Bl/6 mice. Tumors originated from Tm1G3 were larger in tumor volume with enlarged functional vessels, decreased necrotic areas, and increased vascular endothelial growth factor (VEGF) protein levels. Galectin-3-nonexpressing-cells injected into WT and KO showed increased levels of transforming growth factor beta 1 (TGFβ1) and, in WT animals this feature was also accompanied by increased VEGFR2 expression and its phosphorylation. In KO animals, tumors derived from galectin-3-expressing cells were infiltrated by CD68 + -cells, whereas in tumors derived from galectin-3-nonexpressing-cells, CD68 + cells failed to infiltrate tumors and accumulated in the periphery of the tumor mass. In vitro studies showed that Tm1G3 secreted more VEGF than Tm1N3 cells. In the latter case, TGFβ1 induced VEGF production. Basal secretion of VEGF was higher in WT-bone marrow-derived macrophages (BMDM) than in KO-BMDM. TGFβ1 induced secretion of VEGF only in WT-BMDM. Tm1G3-induced tumors had the Arginase I mRNA increased, which upregulated alternative macrophage (M2)/TAM induction. M2 stimuli, such as interleukin-4 (IL4) and TGFβ1, increased Arginase I protein levels and galectin-3 expression in WT- BMDM, but not in cells from KO mice. Hence, we report that galectin-3 disruption in tumor stroma and parenchyma decreases angiogenesis through interfering with the responses of macrophages to the interdependent VEGF and TGFβ1 signaling pathways

Extremely fast vertical displacement event induced by a plasma βp collapse in high βp tokamak disruptions

International Nuclear Information System (INIS)

Nakamura, Yukiharu; Yoshino, Ryuji; Pomphrey, N.; Jardin, S.C.

1996-05-01

In a vertically elongated (κ ∼ 1.5), high β p (β p ∼ 1.7) tokamak with a resistive shell, extremely fast vertical displacement events (VDE's) induced by a model of strong β p collapse were found through computer simulations using the Tokamak Simulation Code. Although the plasma current quench, which had been shown to be the prime cause of VDE's in a relatively low β p tokamak (β p ∼ 0.2), was not observed during the VDE evolution, the observed growth rate of VDE's was almost five times (γ ∼ 655 sec -1 ) faster than the growth rate of the usual positional instability (γ ∼ 149 sec -1 ). The essential mechanism of the β p collapse-induced VDE was clarified to be the significant destabilization of positional instability due to a large and sudden degradation of the decay n-index in addition to a reduction of the stability index n s . It is pointed out that the shell-geometry characterizes the VDE dynamics, and that the VDE rate depends strongly both on the magnitude of the β p collapse and the n-index of the equilibria just before the β p collapse occurs. A new guide line for designing the fusion reactor is proposed with considering the impact of disruptions. (author)

Energy flux to the TEXTOR limiters during disruptions

International Nuclear Information System (INIS)

Finken, K.H.; Baek, W.Y.; Dippel, K.H.; Boedo, J.A.; Gray, D.S.

1992-01-01

Rapidly changing heat fluxes deposited on the limiter blades are observed during disruptions by infrared (IR) scanners. These scanners are a suitable tool for the analysis of these heat fluxes because they provide both spatial and temporal information with sufficient resolution. Several new features of the power flux to the plasma facing surfaces during a disruption have been found. The disruptive heat flux occurs on three different time-scales. The fastest ones are for heat bursts with a duration of ≤0.1 ms; several of these bursts form a thermal quench of about one millisecond duration, and some of these thermal quenches are found to occur during the current decay phase. Power flux densities of the order of 50 MW/m 2 have been observed during a burst. The spatial extent of the area on which this power is deposited during a burst is larger than or equal to the size of half an ALT-II blade, i.e. about 1 m in the toroidal direction. Simultaneous measurements with two cameras show that the correlation length of a single burst is smaller than half the toroidal circumference, probably of the order of half a blade or a full blade length. This is consistent with plasma islands of low mode number. The typical heat deposition patterns at the limiter blades for normal discharges are preserved during a disruption. The magnetic structure near the plasma surface can therefore not be destroyed completely during the thermal quench. The power flux follows the field lines. However, the power e-folding length is about a factor of two to three times larger than under normal discharge conditions. (author). 27 refs, 9 figs

Disruption of gut homeostasis by opioids accelerates HIV disease progression

Directory of Open Access Journals (Sweden)

Jingjing eMeng

2015-06-01

Full Text Available Cumulative studies during the past 30 years have established the correlation between opioid abuse and human immunodeficiency virus (HIV infection. Further studies also demonstrate that opioid addiction is associated with faster progression to AIDS in patients. Recently, it was revealed that disruption of gut homeostasis and subsequent microbial translocation play important roles in pathological activation of the immune system during HIV infection and contributes to accelerated disease progression. Similarly, opioids have been shown to modulate gut immunity and induce gut bacterial translocation. This review will explore the mechanisms by which opioids accelerate HIV disease progression by disrupting gut homeostasis. Better understanding of these mechanisms will facilitate the search for new therapeutic interventions to treat HIV infection especially in opioid abusing population.

Characterization of axisymmetric disruption dynamics toward VDE avoidance in tokamaks

International Nuclear Information System (INIS)

Nakamura, Y.

2002-01-01

Disruption experiments on Alcator C-Mod and ASDEX-Upgrade tokamaks and axisymmetric MHD simulations using the TSC have explicated the underlying mechanisms of Vertical Displacement Events (VDEs) and a diversity of disruption dynamics. First, the neutral point, which is known as an initial vertical plasma position advantageous to VDE avoidance, is shown to be fairly insensitive to plasma shape and current profile parameters, while the VDE rate significantly depends on those parameters. Secondly, it is clarified that a rapid flattening of the plasma current profile frequently seen at the thermal quench drags a single null-diverted, up-down asymmetric plasma vertically toward divertor, whereas the dragging effect is absent in up-down symmetric limiter discharges. As a consequence, the occurrence of downward-going VDEs predominates over the upward-going ones in bottom-diverted discharges, being consistent with experiments in ASDEX-Upgrade. Together with the attractive force that arises from passive shell currents induced by the current quench and vanishes at the neutral point, the dragging effect explains many details of the VDE dynamics over the whole period of disruptive termination. (author)

Disruption of the mouse Jhy gene causes abnormal ciliary microtubule patterning and juvenile hydrocephalus

Science.gov (United States)

Appelbe, Oliver K.; Bollman, Bryan; Attarwala, Ali; Triebes, Lindy A.; Muniz-Talavera, Hilmarie; Curry, Daniel J.; Schmidt, Jennifer V.

2013-01-01

SUMMARY Congenital hydrocephalus, the accumulation of excess cerebrospinal fluid (CSF) in the ventricles of the brain, affects one of every 1,000 children born today, making it one of the most common human developmental disorders. Genetic causes of hydrocephalus are poorly understood in humans, but animal models suggest a broad genetic program underlying the regulation of CSF balance. In this study, the random integration of a transgene into the mouse genome led to the development of an early onset and rapidly progressive hydrocephalus. Juvenile hydrocephalus transgenic mice (JhylacZ) inherit communicating hydrocephalus in an autosomal recessive fashion with dilation of the lateral ventricles observed as early as postnatal day 1.5. Ventricular dilation increases in severity over time, becoming fatal at 4-8 weeks of age. The ependymal cilia lining the lateral ventricles are morphologically abnormal and reduced in number in JhylacZ/lacZ brains, and ultrastructural analysis revealed disorganization of the expected 9+2 microtubule pattern. Rather, the majority of JhylacZ/lacZ cilia develop axonemes with 9+0 or 8+2 microtubule structures. Disruption of an unstudied gene, 4931429I11Rik (now named Jhy) appears to underlie the hydrocephalus of JhylacZ/lacZ mice, and the Jhy transcript and protein are decreased in JhylacZ/lacZ mice. Partial phenotypic rescue was achieved in JhylacZ/lacZ mice by the introduction of a bacterial artificial chromosome (BAC) carrying 60-70% of the JHY protein coding sequence. Jhy is evolutionarily conserved from humans to basal vertebrates, but the predicted JHY protein lacks identifiable functional domains. Ongoing studies are directed at uncovering the physiological function of JHY and its role in CSF homeostasis. PMID:23906841

Self-Organized Patterns Induced by Neimark-Sacker, Flip and Turing Bifurcations in a Discrete Predator-Prey Model with Lesie-Gower Functional Response

Directory of Open Access Journals (Sweden)

Feifan Zhang

2017-06-01

Full Text Available The formation of self-organized patterns in predator-prey models has been a very hot topic recently. The dynamics of these models, bifurcations and pattern formations are so complex that studies are urgently needed. In this research, we transformed a continuous predator-prey model with Lesie-Gower functional response into a discrete model. Fixed points and stability analyses were studied. Around the stable fixed point, bifurcation analyses including: flip, Neimark-Sacker and Turing bifurcation were done and bifurcation conditions were obtained. Based on these bifurcation conditions, parameters values were selected to carry out numerical simulations on pattern formation. The simulation results showed that Neimark-Sacker bifurcation induced spots, spirals and transitional patterns from spots to spirals. Turing bifurcation induced labyrinth patterns and spirals coupled with mosaic patterns, while flip bifurcation induced many irregular complex patterns. Compared with former studies on continuous predator-prey model with Lesie-Gower functional response, our research on the discrete model demonstrated more complex dynamics and varieties of self-organized patterns.

Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

Science.gov (United States)

Kusano, Toshiki; Kurashige, Hiroki; Nambu, Isao; Moriguchi, Yoshiya; Hanakawa, Takashi; Wada, Yasuhiro; Osu, Rieko

2015-08-01

It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

Maternal and Early-Life Circadian Disruption Have Long-Lasting Negative Consequences on Offspring Development and Adult Behavior in Mice.

Science.gov (United States)

Smarr, Benjamin L; Grant, Azure D; Perez, Luz; Zucker, Irving; Kriegsfeld, Lance J

2017-06-12

Modern life involves chronic circadian disruption through artificial light and these disruptions are associated with numerous mental and physical health maladies. Because the developing nervous system is particularly vulnerable to perturbation, we hypothesized that early-life circadian disruption would negatively impact offspring development and adult function. Pregnant mice were subjected to chronic circadian disruption from the time of uterine implantation through weaning. To dissociate in utero from postnatal effects, a subset of litters was cross-fostered at birth from disrupted dams to control dams and vice versa. Postnatal circadian disruption was associated with reduced adult body mass, social avoidance, and hyperactivity. In utero disruption resulted in more pronounced social avoidance and hyperactivity, phenotypes not abrogated by cross-fostering to control mothers. To examine whether circadian disruption affects development by acting as an early life stressor, we examined birthweight, litter size, maternal cannibalism, and epigenetic modifications. None of these variables differed between control and disrupted dams, or resembled patterns seen following early-life stress. Our findings indicate that developmental chronic circadian disruption permanently affects somatic and behavioral development in a stage-of-life-dependent manner, independent of early life stress mechanisms, underscoring the importance of temporal structure during development, both in utero and early postnatal life.

T-tubule disruption promotes calcium alternans in failing ventricular myocytes: mechanistic insights from computational modeling.

Science.gov (United States)

Nivala, Michael; Song, Zhen; Weiss, James N; Qu, Zhilin

2015-02-01

In heart failure (HF), T-tubule (TT) disruption contributes to dyssynchronous calcium (Ca) release and impaired contraction, but its role in arrhythmogenesis remains unclear. In this study, we investigate the effects of TT disruption and other HF remodeling factors on Ca alternans in ventricular myocytes using computer modeling. A ventricular myocyte model with detailed spatiotemporal Ca cycling modeled by a coupled Ca release unit (CRU) network was used, in which the L-type Ca channels and the ryanodine receptor (RyR) channels were simulated by random Markov transitions. TT disruption, which removes the L-type Ca channels from the associated CRUs, results in "orphaned" RyR clusters and thus provides increased opportunity for spark-induced Ca sparks to occur. This effect combined with other HF remodeling factors promoted alternans by two distinct mechanisms: 1) for normal sarco-endoplasmic reticulum Ca ATPase (SERCA) activity, alternans was caused by both CRU refractoriness and coupling. The increased opportunity for spark-induced sparks by TT disruption combined with the enhanced CRU coupling by Ca elevation in the presence or absence of increased RyR leakiness facilitated spark synchronization on alternate beats to promote Ca alternans; 2) for down-regulated SERCA, alternans was caused by the sarcoplasmic reticulum (SR) Ca load-dependent mechanism, independent of CRU refractoriness. TT disruption and increased RyR leakiness shifted and steepened the SR Ca release-load relationship, which combines with down-regulated SERCA to promote Ca alternans. In conclusion, the mechanisms of Ca alternans for normal and down-regulated SERCA are different, and TT disruption promotes Ca alternans by both mechanisms, which may contribute to alternans at different stages of HF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of disrupted mitochondria as a source of damage-associated molecular patterns on the production of tumor necrosis factor α by splenocytes from dogs.

Science.gov (United States)

Friedenberg, Steven G; Strange, Heather R; Guillaumin, Julien; VanGundy, Zachary C; Crouser, Elliott D; Papenfuss, Tracey L

2016-06-01

OBJECTIVE To evaluate the effects of damage-associated molecular patterns (DAMPs) derived from disrupted mitochondria on canine splenocytes and other immune cells. SAMPLES Liver, spleen, and bone marrow samples obtained from 8 cadavers of healthy research Beagles that had been euthanized for other purposes. PROCEDURES Mitochondria were obtained from canine hepatocytes, and mitochondrial DAMPs (containing approx 75% mitochondrial proteins) were prepared. Mitochondrial DAMPs and the nuclear cytokine high-mobility group box protein 1 were applied to splenocytes, bone marrow-differentiated dendritic cells, and a canine myelomonocytic cell (DH82) line for 6 or 24 hours. Cell culture supernatants from splenocytes, dendritic cells, and DH82 cells were assayed for tumor necrosis factor α with an ELISA. Expression of tumor necrosis factor α mRNA in splenocytes was evaluated with a quantitative real-time PCR assay. RESULTS In all cell populations evaluated, production of tumor necrosis factor α was consistently increased by mitochondrial DAMPs at 6 hours (as measured by an ELISA). In contrast, high-mobility group box protein 1 did not have any independent proinflammatory effects in this experimental system. CONCLUSIONS AND CLINICAL RELEVANCE The study revealed an in vitro inflammatory effect of mitochondrial DAMPs (containing approx 75% mitochondrial proteins) in canine cells and validated the use of an in vitro splenocyte model to assess DAMP-induced inflammation in dogs. This experimental system may aid in understanding the contribution of DAMPs to sepsis and the systemic inflammatory response syndrome in humans. Further studies in dogs are needed to validate the biological importance of these findings and to evaluate the in vivo role of mitochondrial DAMPs in triggering and perpetuating systemic inflammatory states.

Current disruption in toroidal devices

International Nuclear Information System (INIS)

1979-07-01

Attempts at raising the density or the plasma current in a tokamak above certain critical values generally result in termination of the discharge by a disruption. This sudden end of the plasma current and plasma confinement is accompanied by large induced voltages and currents in the outer structures which, in large tokamaks, can only be handled with considerable effort, and which will probably only be tolerable in reactors as rare accidents. Because of its crucial importance for the construction and operation of tokamaks, this phenomenon and its theoretical interpretation were the subject of a three-day symposium organized by the International Atomic Energy Agency and Max-Planck-Institut fuer Plasmaphysik at Garching from February 14 to 16. (orig./HT)

Localized electric field induced transition and miniaturization of two-phase flow patterns inside microchannels.

Science.gov (United States)

Sharma, Abhinav; Tiwari, Vijeet; Kumar, Vineet; Mandal, Tapas Kumar; Bandyopadhyay, Dipankar

2014-10-01

Strategic application of external electrostatic field on a pressure-driven two-phase flow inside a microchannel can transform the stratified or slug flow patterns into droplets. The localized electrohydrodynamic stress at the interface of the immiscible liquids can engender a liquid-dielectrophoretic deformation, which disrupts the balance of the viscous, capillary, and inertial forces of a pressure-driven flow to engender such flow morphologies. Interestingly, the size, shape, and frequency of the droplets can be tuned by varying the field intensity, location of the electric field, surface properties of the channel or fluids, viscosity ratio of the fluids, and the flow ratio of the phases. Higher field intensity with lower interfacial tension is found to facilitate the oil droplet formation with a higher throughput inside the hydrophilic microchannels. The method is successful in breaking down the regular pressure-driven flow patterns even when the fluid inlets are exchanged in the microchannel. The simulations identify the conditions to develop interesting flow morphologies, such as (i) an array of miniaturized spherical or hemispherical or elongated oil drops in continuous water phase, (ii) "oil-in-water" microemulsion with varying size and shape of oil droplets. The results reported can be of significance in improving the efficiency of multiphase microreactors where the flow patterns composed of droplets are preferred because of the availability of higher interfacial area for reactions or heat and mass exchange. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MicroRNA expression profile and functional analysis reveal their roles in contact inhibition and its disruption switch of rat vascular smooth muscle cells.

Science.gov (United States)

Sun, Ye-Ying; Qin, Shan-Shan; Cheng, Yun-Hui; Wang, Chao-Yun; Liu, Xiao-Jun; Liu, Ying; Zhang, Xiu-Li; Zhang, Wendy; Zhan, Jia-Xin; Shao, Shuai; Bian, Wei-Hua; Luo, Bi-Hui; Lu, Dong-Feng; Yang, Jian; Wang, Chun-Hua; Zhang, Chun-Xiang

2018-05-01

Contact inhibition and its disruption of vascular smooth muscle cells (VSMCs) are important cellular events in vascular diseases. But the underlying molecular mechanisms are unclear. In this study we investigated the roles of microRNAs (miRNAs) in the contact inhibition and its disruption of VSMCs and the molecular mechanisms involved. Rat VSMCs were seeded at 30% or 90% confluence. MiRNA expression profiles in contact-inhibited confluent VSMCs (90% confluence) and non-contact-inhibited low-density VSMCs (30% confluence) were determined. We found that multiple miRNAs were differentially expressed between the two groups. Among them, miR-145 was significantly increased in contact-inhibited VSMCs. Serum could disrupt the contact inhibition as shown by the elicited proliferation of confluent VSMCs. The contact inhibition disruption accompanied with a down-regulation of miR-145. Serum-induced contact inhibition disruption of VSMCs was blocked by overexpression of miR-145. Moreover, downregulation of miR-145 was sufficient to disrupt the contact inhibition of VSMCs. The downregulation of miR-145 in serum-induced contact inhibition disruption was related to the activation PI3-kinase/Akt pathway, which was blocked by the PI3-kinase inhibitor LY294002. KLF5, a target gene of miR-145, was identified to be involved in miR-145-mediated effect on VSMC contact inhibition disruption, as it could be inhibited by knockdown of KLF5. In summary, our results show that multiple miRNAs are differentially expressed in contact-inhibited VSMCs and in non-contact-inhibited VSMCs. Among them, miR-145 is a critical gene in contact inhibition and its disruption of VSMCs. PI3-kinase/Akt/miR-145/KLF5 is a critical signaling pathway in serum-induced contact inhibition disruption. Targeting of miRNAs related to the contact inhibition of VSMCs may represent a novel therapeutic approach for vascular diseases.

Disruptive Intelligence - How to gather Information to deal with disruptive innovations

NARCIS (Netherlands)

Vriens, D.J.; Solberg Søilen, K.

2014-01-01

Disruptive innovations are innovations that have the capacity to transform a whole business into one with products that are more accessible and affordable (cf. Christensen et al. 2009). As Christensen et al. argue no business is immune to such disruptive innovations. If these authors are right, it

Recent Advances on Endocrine Disrupting Effects of UV Filters

Directory of Open Access Journals (Sweden)

Jiaying Wang

2016-08-01

Full Text Available Ultraviolet (UV filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives.

Dielectrophoretic deformation of thin liquid films induced by surface charge patterns on dielectric substrates

NARCIS (Netherlands)

Berendsen, C.W.J.; Kuijpers, C.J.; Zeegers, J.C.H.; Darhuber, A.A.

2013-01-01

We studied the deformation of thin liquid films induced by surface charge patterns at the solid–liquid interface quantitatively by experiments and numerical simulations. We deposited a surface charge distribution on dielectric substrates by applying potential differences between a conductive liquid

Persistent aryl hydrocarbon receptor inducers increase with altitude, and estrogen-like disrupters are low in soils of the Alps.

Science.gov (United States)

Levy, Walkiria; Henkelmann, Bernhard; Bernhöft, Silke; Bovee, Toine; Buegger, Franz; Jakobi, Gert; Kirchner, Manfred; Bassan, Rodolfo; Kräuchi, Norbert; Moche, Wolfgang; Offenthaler, Ivo; Simončič, Primoz; Weiss, Peter; Schramm, Karl-Werner

2011-01-01

Soil samples from remote Alpine areas were analyzed for polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans and polychlorinated biphenyls by high-resolution gas chromatography/high-resolution gas spectrometry. Additionally, the EROD micro-assay and a genetically modified yeast estrogen bioassay were carried out to determine persistent aryl hydrocarbon receptors (AhR) and estrogen receptors (ER) agonists, respectively. Regarding the AhR agonists, the toxicity equivalents of analytical and EROD determined values were compared, targeting both altitude of samples and their soil organic content. The ratio between bioassay derived equivalents and analytical determinations suggested no significant contribution of unknown AhR inducers in these sampling sites and some antagonism in soils with relatively high PCB loading. More CYP1A1 expression was induced at the highest sites or about 1400-1500 m a.s.l. along the altitude profiles. Surprisingly, no clear tendencies with the soil organic content were found for dioxin-like compounds. Mean values obtained in the present study were for ER agonists, 2: 0.37±0.12ng 17ß-estradiol EQ g-1 dry soil [corrected] and 6.1 ± 4.2 pg TCDD-EQ g⁻¹ dry soil for AhR agonists. Low bioassay responses with a higher relative amount of ER disrupters than AhR inducers were detected,indicating the higher abundance of estrogen-like than persistent dioxin-like compounds in these forested areas [corrected].

Quantitative Proteomic Analysis of Staphylococcus aureus Treated With Punicalagin, a Natural Antibiotic From Pomegranate That Disrupts Iron Homeostasis and Induces SOS.

Science.gov (United States)

Cooper, Bret; Islam, Nazrul; Xu, Yunfeng; Beard, Hunter S; Garrett, Wesley M; Gu, Ganyu; Nou, Xiangwu

2018-05-01

Staphylococcus aureus, a bacterial, food-borne pathogen of humans, can contaminate raw fruits and vegetables. While physical and chemical methods are available to control S. aureus, scientists are searching for inhibitory phytochemicals from plants. One promising compound from pomegranate is punicalagin, a natural antibiotic. To get a broader understanding of the inhibitory effect of punicalagin on S. aureus growth, high-throughput mass spectrometry and quantitative isobaric labeling was used to investigate the proteome of S. aureus after exposure to a sublethal dose of punicalagin. Nearly half of the proteins encoded by the small genome were interrogated, and nearly half of those exhibited significant changes in accumulation. Punicalagin treatment altered the accumulation of proteins and enzymes needed for iron acquisition, and it altered amounts of enzymes for glycolysis, citric acid cycling, protein biosynthesis, and purine and pyrimidine biosynthesis. Punicalagin treatment also induced an SOS cellular response to damaged DNA. Transcriptional comparison of marker genes shows that the punicalagin-induced iron starvation and SOS responses resembles those produced by EDTA and ciprofloxacin. These results show that punicalagin adversely alters bacterial growth by disrupting iron homeostasis and that it induces SOS, possibly through DNA biosynthesis inhibition. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anisotropic photoconductivity and current deflection induced in Bi12SiO20 by high contrast interference pattern

DEFF Research Database (Denmark)

Kukhtarev, N.V.; Lyuksyutov, S; Buchhave, Preben

1996-01-01

We have predicted and observed an anisotropic photocurrent induced in the cubic crystal Bi/sub 12/SiO/sub 20/ by a high-contrast interference pattern. The transverse current detected when the interference pattern is tilted is caused by deflection of the direct current generated by an external...

Politisk disruption

DEFF Research Database (Denmark)

Tække, Jesper

2018-01-01

Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på.......Dette blogindlæg giver en kort analyse af hvordan de sociale medier ved at give en ny tid har åbnet for den disruption af de politiske processer som især Trump stå som et eksempel på....

Benzopyrene exposure disrupts DNA methylation and growth dynamics in breast cancer cells

International Nuclear Information System (INIS)

Sadikovic, Bekim; Rodenhiser, David I.

2006-01-01

Exposures to environmental carcinogens and unhealthy lifestyle choices increase the incidence of breast cancer. One such compound, benzo(a)pyrene (BaP), leads to covalent DNA modifications and the deregulation of gene expression. To date, these mechanisms of BaP-induced carcinogenesis are poorly understood, particularly in the case of breast cancer. We tested the effects of BaP exposure on cellular growth dynamics and DNA methylation in four breast cancer cell lines since disruptions in DNA methylation lead to deregulated gene expression and the loss of genomic integrity. We observed robust time- and concentration-dependent loss of proliferation, S phase and G2M accumulation and apoptosis in p53 positive MCF-7 and T47-D cells. We observed minimal responses in p53 negative HCC-1086 and MDA MB 231 cells. Furthermore, BaP increased p53 levels in both p53 positive cell lines, as well as p21 levels in MCF-7 cells, an effect that was prevented by the p53-specific inhibitor pifithrin-α. No changes in global levels of DNA methylation levels induced by BaP were detected by the methyl acceptor assay (MAA) in any cell line, however, methylation profiling by AIMS (amplification of intermethylated sites) analysis showed dynamic, sequence-specific hypo- and hypermethylation events in all cell lines. We also identified BaP-induced hypomethylation events at a number of genomic repeats. Our data confirm the p53-specific disruption of the cell cycle as well as the disruption of DNA methylation as a consequence of BaP treatment, thus reinforcing the link between environmental exposures, DNA methylation and breast cancer

Nanosecond pulsed laser induced self-organized nano-dots patterns on GaSb surface

Energy Technology Data Exchange (ETDEWEB)

Yoshida, Yutaka, E-mail: yyoshida@cris.hokudai.ac.jp [Center for Advanced Research of Energy and Materials, Faculty of Engineering, Hokkaido University, N8, W13, Kita-ku, Sapporo 060-8628, Hokkaido (Japan); Creative Research Institution Sousei, Hokkaido University, N21, W10, Kita-ku, Sapporo 001-0021, Hokkaido (Japan); Oosawa, Kazuya; Wajima, Jyunya; Watanabe, Seiichi [Center for Advanced Research of Energy and Materials, Faculty of Engineering, Hokkaido University, N8, W13, Kita-ku, Sapporo 060-8628, Hokkaido (Japan); Matsuo, Yasutaka [Research Institute for Electronic Science, Hokkaido University, Sapporo 001-0020, Hokkaido (Japan); Kato, Takahiko [Hitachi Research Laboratory, Hitachi, Ltd., 7-1-1 Omika, Hitachi-shi 319-1292, Ibaraki-ken (Japan); Center for Advanced Research of Energy and Materials, Faculty of Engineering, Hokkaido University, N8, W13, Kita-ku, Sapporo 060-8628, Hokkaido (Japan)

2014-07-01

We report a technique for formation of two-dimensional (2D) nanodot (ND) patterns on gaillium antimoide (GaSb) using a nanosecond pulsed laser irradiation with 532 nm wavelength. The patterns have formed because of the interference and the self-organization under energy deposition of the laser irradiation, which induced the growth of NDs on the local area. The NDs are grown and shrunken in the pattern by energy depositions. In the laser irradiation with average laser energy density of 35 mJ cm⁻², large and small NDs are formed on GaSb surface. The large NDs have grown average diameter from 160 to 200 nm with increase of laser pulses, and the small NDs have shrunken average diameter from 75 to 30 nm. The critical dot size is required about 107 nm for growth of the NDs in the patterns. Nanosecond pulsed laser irradiation can control the self-organized ND size on GaSb in air as a function of the laser pulses.

Towards a Disruptive Digital Platform Model

DEFF Research Database (Denmark)

Kazan, Erol

that digital platforms leverage on three strategic design elements (i.e., business, architecture, and technology design) to create supportive conditions for facilitating disruption. To shed light on disruptive digital platforms, I opted for payment platforms as my empirical context and unit of analysis......Digital platforms are layered modular information technology architectures that support disruption. Digital platforms are particularly disruptive, as they facilitate the quick release of digital innovations that may replace established innovations. Yet, despite their support for disruption, we have...... not fully understood how such digital platforms can be strategically designed and configured to facilitate disruption. To that end, this thesis endeavors to unravel disruptive digital platforms from the supply perspective that are grounded on strategic digital platform design elements. I suggest...

Polycyclic aromatic hydrocarbons disrupt axial development in sea urchin embryos through a β-catenin dependent pathway

International Nuclear Information System (INIS)

Pillai, Murali C.; Vines, Carol A.; Wikramanayake, Athula H.; Cherr, Gary

2003-01-01

Sea urchin (Lytechinus anemesis) embryos were used as an experimental system to investigate the mechanisms of the developmental toxicity of creosote, one of the most widely used wood preserving chemicals, as well as some of its polycyclic aromatic hydrocarbon (PAH) constituents (phenanthrene, fluoranthene, fluorene, pyrene and quinoline). Data suggest that creosote and PAHs affect axial development and patterning in sea urchin embryos by disrupting the regulation of β-catenin, a crucial transcriptional co-activator of specific target genes in the Wnt/wg signaling pathway. When ciliated blastula stage embryos were exposed to these compounds, they developed into exogastrulae with completely evaginated archentera, demonstrating that these chemicals disrupt axial development and patterning. This response occurred in a dose-dependent fashion, with the EC 50 of creosote for complete exogastrulation being 1.57 ppm, while the EC 50 s of the PAHs ranged from 0.41 ppm (2.0 μM) to 4.33 ppm (33.5 μM). Morphologically, the exogastrulae that developed from embryos exposed to creosote and PAHs appeared to be identical to those that resulted from exposure to lithium chloride, a classical agent known to induce vegetalization and exogastrulation in sea urchin embryos. Immunological studies using antibodies against β-catenin, a multi-functional protein known to be involved in cell-cell adhesion and cell fate specification during embryonic development, revealed high levels of nuclear accumulation of β-catenin by cells of creosote- and PAH-exposed embryos, irrespective of their positions in the developing embryo. Dissociated embryonic cells cultured in the presence of these agents rapidly responded in a similar fashion. Since β-catenin accumulation occurs in nuclei of several types of cancer cells, it is possible this may be a general mechanism by which PAHs affect a variety of different cell types

Thigmotaxis Mediates Trail Odour Disruption.

Science.gov (United States)

Stringer, Lloyd D; Corn, Joshua E; Sik Roh, Hyun; Jiménez-Pérez, Alfredo; Manning, Lee-Anne M; Harper, Aimee R; Suckling, David M

2017-05-10

Disruption of foraging using oversupply of ant trail pheromones is a novel pest management application under investigation. It presents an opportunity to investigate the interaction of sensory modalities by removal of one of the modes. Superficially similar to sex pheromone-based mating disruption in moths, ant trail pheromone disruption lacks an equivalent mechanistic understanding of how the ants respond to an oversupply of their trail pheromone. Since significant compromise of one sensory modality essential for trail following (chemotaxis) has been demonstrated, we hypothesised that other sensory modalities such as thigmotaxis could act to reduce the impact on olfactory disruption of foraging behaviour. To test this, we provided a physical stimulus of thread to aid trailing by Argentine ants otherwise under disruptive pheromone concentrations. Trail following success was higher using a physical cue. While trail integrity reduced under continuous over-supply of trail pheromone delivered directly on the thread, provision of a physical cue in the form of thread slightly improved trail following and mediated trail disruption from high concentrations upwind. Our results indicate that ants are able to use physical structures to reduce but not eliminate the effects of trail pheromone disruption.

Supply disruption cost for power network planning

International Nuclear Information System (INIS)

Kjoelle, G.H.

1992-09-01

A description is given of the method of approach to calculate the total annual socio-economic cost of power supply disruption and non-supplied energy, included the utilities' cost for planning. The total socio-economic supply disruption cost is the sum of the customers' disruption cost and the utilities' cost for failure and disruption. The mean weighted disruption cost for Norway for one hour disruption is NOK 19 per kWh. The customers' annual disruption cost is calculated with basis in the specific disruption cost referred to heavy load (January) and dimensioning maximum loads. The loads are reduced by factors taking into account the time variations of the failure frequency, duration, the loads and the disruption cost. 6 refs

Disrupting the Industry with Play

DEFF Research Database (Denmark)

Lund, Henrik Hautop

2016-01-01

or two ago. This is significantly disrupting the industry in several market sectors. This paper describes the components of the playware and embodied artificial intelligence research that has led to disruption in the industrial robotics sector, and which points to the next disruption of the health care...

Cell disruption for microalgae biorefineries.

Science.gov (United States)

Günerken, E; D'Hondt, E; Eppink, M H M; Garcia-Gonzalez, L; Elst, K; Wijffels, R H

2015-01-01

Microalgae are a potential source for various valuable chemicals for commercial applications ranging from nutraceuticals to fuels. Objective in a biorefinery is to utilize biomass ingredients efficiently similarly to petroleum refineries in which oil is fractionated in fuels and a variety of products with higher value. Downstream processes in microalgae biorefineries consist of different steps whereof cell disruption is the most crucial part. To maintain the functionality of algae biochemicals during cell disruption while obtaining high disruption yields is an important challenge. Despite this need, studies on mild disruption of microalgae cells are limited. This review article focuses on the evaluation of conventional and emerging cell disruption technologies, and a comparison thereof with respect to their potential for the future microalgae biorefineries. The discussed techniques are bead milling, high pressure homogenization, high speed homogenization, ultrasonication, microwave treatment, pulsed electric field treatment, non-mechanical cell disruption and some emerging technologies. Copyright © 2015 Elsevier Inc. All rights reserved.

The effects of chronic social defeat stress on mouse self-grooming behavior and its patterning.

Science.gov (United States)

Denmark, Ashley; Tien, David; Wong, Keith; Chung, Amanda; Cachat, Jonathan; Goodspeed, Jason; Grimes, Chelsea; Elegante, Marco; Suciu, Christopher; Elkhayat, Salem; Bartels, Brett; Jackson, Andrew; Rosenberg, Michael; Chung, Kyung Min; Badani, Hussain; Kadri, Ferdous; Roy, Sudipta; Tan, Julia; Gaikwad, Siddharth; Stewart, Adam; Zapolsky, Ivan; Gilder, Thomas; Kalueff, Allan V

2010-04-02

Stress induced by social defeat is a strong modifier of animal anxiety and depression-like phenotypes. Self-grooming is a common rodent behavior, and has an ordered cephalo-caudal progression from licking of the paws to head, body, genitals and tail. Acute stress is known to alter grooming activity levels and disrupt its patterning. Following 15-17 days of chronic social defeat stress, grooming behavior was analyzed in adult male C57BL/6J mice exhibiting either dominant or subordinate behavior. Our study showed that subordinate mice experience higher levels of anxiety and display disorganized patterning of their grooming behaviors, which emerges as a behavioral marker of chronic social stress. These findings indicate that chronic social stress modulates grooming behavior in mice, thus illustrating the importance of grooming phenotypes for neurobehavioral stress research. Copyright 2010 Elsevier B.V. All rights reserved.

Disruptive Technology Enhanced Learning: The Use and Misuse of Digital Technologies in Higher Education

Science.gov (United States)

Flavin, Michael

2017-01-01

This book is about how technologies are used in practice to support learning and teaching in higher education. Despite digitization and e-learning becoming ever-increasingly popular in university teaching settings, this book convincingly argues instead in favour of simple and convenient technologies, thus disrupting traditional patterns of…

Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

Science.gov (United States)

Zhang, Zong-Yong; Jiang, Ming; Fang, Jie; Yang, Ming-Feng; Zhang, Shuai; Yin, Yan-Xin; Li, Da-Wei; Mao, Lei-Lei; Fu, Xiao-Yan; Hou, Ya-Jun; Fu, Xiao-Ting; Fan, Cun-Dong; Sun, Bao-Liang

2017-01-01

Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

Major disruption process in tokamak

International Nuclear Information System (INIS)

Kurita, Gen-ichi; Azumi, Masafumi; Tuda, Takashi; Takizuka, Tomonori; Tsunematsu, Toshihide; Tokuda, Shinji; Itoh, Kimitaka; Takeda, Tatsuoki

1981-11-01

The major disruption in a cylindrical tokamak is investigated by using the multi-helicity code, and the destabilization of the 3/2 mode by the mode coupling with the 2/1 mode is confirmed. The evolution of the magnetic field topology caused by the major disruption is studied in detail. The effect of the internal disruption on the 2/1 magnetic island width is also studied. The 2/1 magnetic island is not enhanced by the flattening of the q-profile due to the internal disruption. (author)

Disruption of the HPA-axis through corticosterone-release pellets induces robust depressive-like behavior and reduced BDNF levels in mice.

Science.gov (United States)

Demuyser, Thomas; Bentea, Eduard; Deneyer, Lauren; Albertini, Giulia; Massie, Ann; Smolders, Ilse

2016-07-28

The corticosterone mouse model is widely used in preclinical research towards a better understanding of mechanisms of major depression. One particular administration procedure is the subcutaneous implantation of corticosterone slow-release pellets. In this report we want to provide basic evidence, regarding behavioral changes, neurotransmitter and -modulator levels and some other relevant biomolecules after hypothalamic-pituitary-adrenal-axis distortion. We show that three weeks of corticosterone pellet exposure robustly induces depressive-like but not anxiety-like behavior in mice, accompanied by a significant decrease in hippocampal brain-derived neurotrophic factor levels, at five weeks after the start of treatment. Furthermore there is an overall decrease in plasma corticosterone levels after three weeks of treatment that lasts up until the five weeks' time point. On the other hand, no differences are observed in total monoamine, glutamate or d-serine levels, nor in glucocorticoid receptor expression, in various depression-related brain areas. Altogether this characterization delivers vital information, supplementary to existing literature, regarding the phenotyping of pellet-induced hypothalamic-pituitary-adrenal-axis disruption in mice following three weeks of continuous corticosterone exposure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nuclear bodies reorganize during myogenesis in vitro and are differentially disrupted by expression of FSHD-associated DUX4

Directory of Open Access Journals (Sweden)

Sachiko Homma

2016-12-01

Full Text Available Abstract Background Nuclear bodies, such as nucleoli, PML bodies, and SC35 speckles, are dynamic sub-nuclear structures that regulate multiple genetic and epigenetic processes. Additional regulation is provided by RNA/DNA handling proteins, notably TDP-43 and FUS, which have been linked to ALS pathology. Previous work showed that mouse cell line myotubes have fewer but larger nucleoli than myoblasts, and we had found that nuclear aggregation of TDP-43 in human myotubes was induced by expression of DUX4-FL, a transcription factor that is aberrantly expressed and causes pathology in facioscapulohumeral dystrophy (FSHD. However, questions remained about nuclear bodies in human myogenesis and in muscle disease. Methods We examined nucleoli, PML bodies, SC35 speckles, TDP-43, and FUS in myoblasts and myotubes derived from healthy donors and from patients with FSHD, laminin-alpha-2-deficiency (MDC1A, and alpha-sarcoglycan-deficiency (LGMD2D. We further examined how these nuclear bodies and proteins were affected by DUX4-FL expression. Results We found that nucleoli, PML bodies, and SC35 speckles reorganized during differentiation in vitro, with all three becoming less abundant in myotube vs. myoblast nuclei. In addition, though PML bodies did not change in size, both nucleoli and SC35 speckles were larger in myotube than myoblast nuclei. Similar patterns of nuclear body reorganization occurred in healthy control, MDC1A, and LGMD2D cultures, as well as in the large fraction of nuclei that did not show DUX4-FL expression in FSHD cultures. In contrast, nuclei that expressed endogenous or exogenous DUX4-FL, though retaining normal nucleoli, showed disrupted morphology of some PML bodies and most SC35 speckles and also co-aggregation of FUS with TDP-43. Conclusions Nucleoli, PML bodies, and SC35 speckles reorganize during human myotube formation in vitro. These nuclear body reorganizations are likely needed to carry out the distinct gene transcription and

Disrupt mig vel: Fire gode råd om disruption

DEFF Research Database (Denmark)

Rydén, Pernille; Ringberg, Torsten; Østergaard Jacobsen, Per

2017-01-01

Forandring. Ønsket om at være teknologisk foran, kommer ofte til at ske på bekostning af fokus på kundernes oplevelser. Lighedstegnet mellem disruption og ny teknologi er kun den halve sandhed.......Forandring. Ønsket om at være teknologisk foran, kommer ofte til at ske på bekostning af fokus på kundernes oplevelser. Lighedstegnet mellem disruption og ny teknologi er kun den halve sandhed....

The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

Science.gov (United States)

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2010-12-26

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in

The disruptive effects of methamphetamine on delayed-matching-to-sample performance reflect proactive interference and are reduced by SCH23390.

Science.gov (United States)

Macaskill, Anne C; Harrow, Catherine C; Harper, David N

2015-01-01

Different drugs produce different patterns of impairment on delayed matching-to-sample tasks. For example, (+/-)3,4-methylenedioxymethamphetamine (MDMA) produces an increase in proactive interference. That is, subjects are less accurate when they are required to make a response different to the one they made on the immediately previous trial. The current study assessed whether methamphetamine also produces this particular pattern of disruption in delayed matching-to-sample performance in rats. Methamphetamine primarily reduced accuracy on trials where the correct response differed from the one made on the previous trial. Thus methamphetamine, like MDMA and other stimulant-based drugs of abuse, increased proactive interference. This impairment was reduced by prior administration of the dopamine D1 antagonist SCH23390. These results further extend a general conclusion that a range of stimulant-based drugs may disrupt working memory function indirectly via a tendency to repeat previously made responses and that this disruption is related to D1 receptor activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one.

Science.gov (United States)

Nie, Lina; Di, Tianqi; Li, Yu; Cheng, Peng; Li, Ming; Gao, Jun

2018-06-23

Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D 2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT 2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT 2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT 2A receptors on dopamine D 2 -mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D 2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D 2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT 2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT 2A and D 2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT 2A receptors mediate maternal behavior is through

Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia.

Science.gov (United States)

Wang, Xijin; Xia, Mingrui; Lai, Yunyao; Dai, Zhengjia; Cao, Qingjiu; Cheng, Zhang; Han, Xue; Yang, Lei; Yuan, Yanbo; Zhang, Yong; Li, Keqing; Ma, Hong; Shi, Chuan; Hong, Nan; Szeszko, Philip; Yu, Xin; He, Yong

2014-07-01

The pathophysiology of chronic schizophrenia may reflect long term brain changes related to the disorder. The effect of chronicity on intrinsic functional connectivity patterns in schizophrenia without the potentially confounding effect of antipsychotic medications, however, remains largely unknown. We collected resting-state fMRI data in 21 minimally treated chronic schizophrenia patients and 20 healthy controls. We computed regional functional connectivity strength for each voxel in the brain, and further divided regional functional connectivity strength into short-range regional functional connectivity strength and long-range regional functional connectivity strength. General linear models were used to detect between-group differences in these regional functional connectivity strength metrics and to further systematically investigate the relationship between these differences and clinical/behavioral variables in the patients. Compared to healthy controls, the minimally treated chronic schizophrenia patients showed an overall reduced regional functional connectivity strength especially in bilateral sensorimotor cortex, right lateral prefrontal cortex, left insula and right lingual gyrus, and these regional functional connectivity strength decreases mainly resulted from disruption of short-range regional functional connectivity strength. The minimally treated chronic schizophrenia patients also showed reduced long-range regional functional connectivity strength in the bilateral posterior cingulate cortex/precuneus, and increased long-range regional functional connectivity strength in the right lateral prefrontal cortex and lingual gyrus. Notably, disrupted short-range regional functional connectivity strength mainly correlated with duration of illness and negative symptoms, whereas disrupted long-range regional functional connectivity strength correlated with neurocognitive performance. All of the results were corrected using Monte-Carlo simulation. This

Disrupting Business

DEFF Research Database (Denmark)

Cox, Geoff; Bazzichelli, Tatiana

Disruptive Business explores some of the interconnections between art, activism and the business concept of disruptive innovation. With a backdrop of the crisis of financial capitalism, austerity cuts in the cultural sphere, the idea is to focus on potential art strategies in relation to a broken...... economy. In a perverse way, we ask whether this presents new opportunities for cultural producers to achieve more autonomy over their production process. If it is indeed possible, or desirable, what alternative business models emerge? The book is concerned broadly with business as material for reinvention...

Sleep disruption in chronic rhinosinusitis.

Science.gov (United States)

Mahdavinia, Mahboobeh; Schleimer, Robert P; Keshavarzian, Ali

2017-05-01

Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression. Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS. Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.

Toxins in botanical dietary supplements: blue cohosh components disrupt cellular respiration and mitochondrial membrane potential.

Science.gov (United States)

Datta, Sandipan; Mahdi, Fakhri; Ali, Zulfiqar; Jekabsons, Mika B; Khan, Ikhlas A; Nagle, Dale G; Zhou, Yu-Dong

2014-01-24

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA "black box" warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3), exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage.

Toxins in Botanical Dietary Supplements: Blue Cohosh Components Disrupt Cellular Respiration and Mitochondrial Membrane Potential

Science.gov (United States)

Datta, Sandipan; Mahdi, Fakhri; Ali, Zulfiqar; Jekabsons, Mika B.; Khan, Ikhlas A.; Nagle, Dale G.; Zhou, Yu-Dong

2014-01-01

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA “Black Box” warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3) exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage. PMID:24328138

Introduction: circadian rhythm and its disruption: impact on reproductive function.

Science.gov (United States)

Casper, Robert F; Gladanac, Bojana

2014-08-01

Almost all forms of life have predictable daily or circadian rhythms in molecular, endocrine, and behavioral functions. In mammals, a central pacemaker located in the suprachiasmatic nuclei coordinates the timing of these rhythms. Daily light exposure that affects the retina of the eye directly influences this area, which is required to align endogenous processes to the appropriate time of day. The present "Views and Reviews" articles discuss the influence of circadian rhythms, especially nightly secretion of melatonin, on reproductive function and parturition. In addition, an examination is made of problems that arise from recurrent circadian rhythm disruption associated with changes in light exposure patterns common to modern day society. Finally, a possible solution to prevent disruptions in circadian phase markers by filtering out short wavelengths from nocturnal light is reviewed. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Colchicine affects cell motility, pattern formation and stalk cell differentiation in Dictyostelium by altering calcium signaling.

Science.gov (United States)

Poloz, Yekaterina; O'Day, Danton H

2012-04-01

Previous work, verified here, showed that colchicine affects Dictyostelium pattern formation, disrupts morphogenesis, inhibits spore differentiation and induces terminal stalk cell differentiation. Here we show that colchicine specifically induces ecmB expression and enhances accumulation of ecmB-expressing cells at the posterior end of multicellular structures. Colchicine did not induce a nuclear translocation of DimB, a DIF-1 responsive transcription factor in vitro. It also induced terminal stalk cell differentiation in a mutant strain that does not produce DIF-1 (dmtA-) and after the treatment of cells with DIF-1 synthesis inhibitor cerulenin (100 μM). This suggests that colchicine induces the differentiation of ecmB-expressing cells independent of DIF-1 production and likely through a signaling pathway that is distinct from the one that is utilized by DIF-1. Depending on concentration, colchicine enhanced random cell motility, but not chemotaxis, by 3-5 fold (10-50 mM colchicine, respectively) through a Ca(2+)-mediated signaling pathway involving phospholipase C, calmodulin and heterotrimeric G proteins. Colchicine's effects were not due to microtubule depolymerization as other microtubule-depolymerizing agents did not have these effects. Finally normal morphogenesis and stalk and spore cell differentiation of cells treated with 10 mM colchicine were rescued through chelation of Ca2+ by BAPTA-AM and EDTA and calmodulin antagonism by W-7 but not PLC inhibition by U-73122. Morphogenesis or spore cell differentiation of cells treated with 50 mM colchicine could not be rescued by the above treatments but terminal stalk cell differentiation was inhibited by BAPTA-AM, EDTA and W-7, but not U-73122. Thus colchicine disrupts morphogenesis and induces stalk cell differentiation through a Ca(2+)-mediated signaling pathway involving specific changes in gene expression and cell motility. Copyright © 2011 International Society of Differentiation. Published by Elsevier B

Characterization of 6,13-bis(triisopropylsilylethynyl) pentacene organic thin film transistors fabricated using pattern-induced confined structure

International Nuclear Information System (INIS)

Kim, Kyohyeok; Kwon, Namyong; Chung, Ilsub

2014-01-01

Bottom gate organic thin film transistors (OTFTs) were fabricated on polyethersulphone substrate using an ink jet printing method. 6,13-bis(triisopropylsilylethynyl) (TIPS) pentacene and poly-4-vinylphenol (PVP) were used as an active material and as a gate insulator, respectively. In an attempt to reduce the coffee stain effect, TIPS pentacene active layer was printed onto the pattern-induced confined structure (PICS) which had been obtained by orthogonally printing Ag electrodes on the pre-printed PVP layer. The resolution of Ag patterns was obtained by modifying the surface energy using UV irradiation and substrate temperature. The channel lengths of the aforementioned PICS OTFTs were in the range of 10 μm to 50 μm. The average mobility and on/off ratio of PICS OTFTs were 0.034 cm 2 /Vs and 10 3 , respectively. - Highlights: • Ink-jet printed bottom gate organic thin film transistor on plastic substrate • Ag lines orthogonally printed on pre-printed poly-4-vinylphenol lines • Pattern-induced confined structures obtained • UV irradiation affects the surface energy and the resolution of the Ag patterns

Cerebral amyloid angiopathy, blood-brain barrier disruption and amyloid accumulation in SAMP8 mice.

Science.gov (United States)

del Valle, Jaume; Duran-Vilaregut, Joaquim; Manich, Gemma; Pallàs, Mercè; Camins, Antoni; Vilaplana, Jordi; Pelegrí, Carme

2011-01-01

Cerebrovascular dysfunction and β-amyloid peptide deposition on the walls of cerebral blood vessels might be an early event in the development of Alzheimer's disease. Here we studied the time course of amyloid deposition in blood vessels and blood-brain barrier (BBB) disruption in the CA1 subzone of the hippocampus of SAMP8 mice and the association between these two variables. We also studied the association between the amyloid deposition in blood vessels and the recently described amyloid clusters in the parenchyma, as well as the association of these clusters with vessels in which the BBB is disrupted. SAMP8 mice showed greater amyloid deposition in blood vessels than age-matched ICR-CD1 control mice. Moreover, at 12 months of age the number of vessels with a disrupted BBB had increased in both strains, especially SAMP8 animals. At this age, all the vessels with amyloid deposition showed BBB disruption, but several capillaries with an altered BBB showed no amyloid on their walls. Moreover, amyloid clusters showed no spatial association with vessels with amyloid deposition, nor with vessels in which the BBB had been disrupted. Finally, we can conclude that vascular amyloid deposition seems to induce BBB alterations, but BBB disruption may also be due to other factors. Copyright © 2011 S. Karger AG, Basel.

A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-κB genome-wide promoter binding during liver regeneration.

Science.gov (United States)

Kuttippurathu, Lakshmi; Patra, Biswanath; Hoek, Jan B; Vadigepalli, Rajanikanth

2016-03-01

Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome-wide binding activity of NF-κB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-κB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-κB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet-independent shift in NF-κB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-κB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-κB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-β, PPAR-γ and C/EBP-α, likely participating in co-regulatory modules with NF-κB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-κB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx.

Understanding disruptions in tokamaksa)

Science.gov (United States)

Zakharov, Leonid E.; Galkin, Sergei A.; Gerasimov, Sergei N.; contributors, JET-EFDA

2012-05-01

This paper describes progress achieved since 2007 in understanding disruptions in tokamaks, when the effect of plasma current sharing with the wall was introduced into theory. As a result, the toroidal asymmetry of the plasma current measurements during vertical disruption event (VDE) on the Joint European Torus was explained. A new kind of plasma equilibria and mode coupling was introduced into theory, which can explain the duration of the external kink 1/1 mode during VDE. The paper presents first results of numerical simulations using a free boundary plasma model, relevant to disruptions.

Electromagnetic analysis of transient disruption forces on the ITER shield modules

International Nuclear Information System (INIS)

Kotulski, J.D.; Coats, R.S.; Pasik, M.F.

2007-01-01

There are potential abnormal operating environments where the disruption of the plasma currents inside a tokamak induce eddy currents in the shield modules. These currents interact with the large magnetic fields to produce forces in the modules which could potentially cause mechanical failure in the modules and vacuum vessel. For this reason the design and qualification of the ITER shield modules requires appropriate high-fidelity electromagnetic simulations that capture the physics of these situations. These simulations need to include an accurate representation of the disruption currents as well as an accurate electromagnetic model of the shield modules. The purpose of this presentation is to describe the electromagnetic analysis that has been completed using the OPERA-3D product to characterize the forces on the shield modules allocated to the US. We first describe the electromagnetic model of the system which consists of the disruption currents and the shield modules attached to the vacuum vessel. The disruption currents are represented in OPERA-3D using superposition of a large number of solenoids with independent time variation to account for the spatial and temporal variation of the plasma current and position. In addition, the simplified electromagnetic model of the shield modules will be described and discussed. Once the modeling has been described the simulation results are presented. The force computation are also presented and the results discussed. These forces are then used by a mechanical analysis program to compute stresses and torques on a module during the disruption of the plasma currents. (orig.)

Blood-Brain Barrier Disruption After Cardiopulmonary Bypass: Diagnosis and Correlation to Cognition.

Science.gov (United States)

Abrahamov, Dan; Levran, Oren; Naparstek, Sharon; Refaeli, Yael; Kaptson, Shani; Abu Salah, Mahmud; Ishai, Yaron; Sahar, Gideon

2017-07-01

Cardiopulmonary bypass (CPB) elicits a systemic inflammatory response that may impair blood-brain barrier (BBB) integrity. BBB disruption can currently be detected by dynamic contrast enhancement magnetic resonance imaging (MRI), reflected by an increase in the permeability constant (K trans ). We aimed to determine (1) whether CPB induces BBB disruption, (2) duration until BBB disruption resolution, and (3) the obtainable correlation between BBB injury (location and intensity) and neurocognitive dysfunction. Seven patients undergoing CPB with coronary artery bypass grafting (CABG) were assigned to serial cerebral designated MRI evaluations, preoperatively and on postoperative day (POD) 1 and 5. Examinations were analyzed for BBB disruption and microemboli using dynamic contrast enhancement MRI and diffusion-weighted imaging methods, respectively. Neuropsychologic tests were performed 1 day preoperatively and on POD 5. A significant local K trans increase (0.03 min -1 vs 0.07 min -1 , p = 0.033) compatible with BBB disruption was evident in 5 patients (71%) on POD 1. Resolution was observed by POD 5 (mean, 0.012 min -1 ). The location of the disruption was most prominent in the frontal lobes (400% vs 150% K trans levels upsurge, p = 0.05). MRI evidence of microembolization was demonstrated in only 1 patient (14%). The postoperative global cognitive score was reduced in all patients (98.2 ± 12 vs 95.1 ± 11, p = 0.032), predominantly in executive and attention (frontal lobe-related) functions (91.8 ± 13 vs 86.9 ± 12, p = 0.042). The intensity of the dynamic contrast enhancement MRI BBB impairment correlated with the magnitude of cognition reduction (r = 0.69, p = 0.04). BBB disruption was evident in most patients, primarily in the frontal lobes. The location and intensity of the BBB disruption, rather than the microembolic load, correlated with postoperative neurocognitive dysfunction. Copyright © 2017 The Society of Thoracic Surgeons. Published by

The habitat disruption induces immune-suppression and oxidative stress in honey bees

OpenAIRE

Morimoto, Tomomi; Kojima, Yuriko; Toki, Taku; Komeda, Yayoi; Yoshiyama, Mikio; Kimura, Kiyoshi; Nirasawa, Keijiro; Kadowaki, Tatsuhiko

2011-01-01

The honey bee is a major insect used for pollination of many commercial crops worldwide. Although the use of honey bees for pollination can disrupt the habitat, the effects on their physiology have never been determined. Recently, honey bee colonies have often collapsed when introduced in greenhouses for pollination in Japan. Thus, suppressing colony collapses and maintaining the number of worker bees in the colonies is essential for successful long-term pollination in greenhouses and recycli...

Endocrine disruptive effects in vitro of conazole antifungals used as pesticides and pharmaceutical

DEFF Research Database (Denmark)

Kjærstad, Mia Birkhøj; Taxvig, Camilla; Nellemann, Christine Lydia

2010-01-01

Widely used conazole antifungals were tested for endocrine disruptive effects using a panel of in vitro assays. They all showed endocrine disrupting potential and ability to act via several different mechanisms. Overall the imidazoles (econazole, ketoconazole, miconazole, prochloraz) were more...... inhibition of enzymes involved in the conversion of progesterone to testosterone. Prochloraz was most potent followed by econazole~miconazole>ketoconazole>tebuconazole>epoxiconazole>propiconazole. In the MCF-7 cell proliferation assay, the conazoles showed anti-estrogenic effect, including aromatase...... inhibition, since they inhibited the response induced by both 17β-estradiol (miconazole>econazole~ketoconazole>prochloraz>tebuconazole>epoxiconazole>propiconazole) and testosterone (econazole>miconazole>prochloraz>ketoconazole>tebuconazole>epoxiconazole>propiconazole). The triazoles were anti...

TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice

Science.gov (United States)

Welford, Abigail F.; Biziato, Daniela; Coffelt, Seth B.; Nucera, Silvia; Fisher, Matthew; Pucci, Ferdinando; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele; Tozer, Gillian M.; Lewis, Claire E.

2011-01-01

Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA4P-treated tumors either by interfering pharmacologically with the CXCL12/CXCR4 axis or by genetically depleting TEMs in tumor-bearing mice markedly increased the efficacy of CA4P treatment. These data suggest that TEMs limit VDA-induced tumor injury and represent a potential target for improving the clinical efficacy of VDA-based therapies. PMID:21490397

Anterior Visceral Endoderm SMAD4 Signaling Specifies Anterior Embryonic Patterning and Head Induction in Mice

Science.gov (United States)

Li, Cuiling; Li, Yi-Ping; Fu, Xin-Yuan; Deng, Chu-Xia

2010-01-01

SMAD4 serves as a common mediator for signaling of TGF-β superfamily. Previous studies illustrated that SMAD4-null mice die at embryonic day 6.5 (E6.5) due to failure of mesoderm induction and extraembryonic defects; however, functions of SMAD4 in each germ layer remain elusive. To investigate this, we disrupted SMAD4 in the visceral endoderm and epiblast, respectively, using a Cre-loxP mediated approach. We showed that mutant embryos lack of SMAD4 in the visceral endoderm (Smad4Co/Co;TTR-Cre) died at E7.5-E9.5 without head-fold and anterior embryonic structures. We demonstrated that TGF-β regulates expression of several genes, such as Hex1, Cer1, and Lim1, in the anterior visceral endoderm (AVE), and the failure of anterior embryonic development in Smad4Co/Co;TTR-Cre embryos is accompanied by diminished expression of these genes. Consistent with this finding, SMAD4-deficient embryoid bodies showed impaired responsiveness to TGF-β-induced gene expression and morphological changes. On the other hand, embryos carrying Cre-loxP mediated disruption of SMAD4 in the epiblasts exhibited relatively normal mesoderm and head-fold induction although they all displayed profound patterning defects in the later stages of gastrulation. Cumulatively, our data indicate that SMAD4 signaling in the epiblasts is dispensable for mesoderm induction although it remains critical for head patterning, which is significantly different from SMAD4 signaling in the AVE, where it specifies anterior embryonic patterning and head induction. PMID:20941375

Thyroid effects of endocrine disrupting chemicals

DEFF Research Database (Denmark)

Boas, Malene; Feldt-Rasmussen, Ulla; Main, Katharina M

2012-01-01

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert ...... thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties....

Methodology for identifying credible disruptions to isolation of nuclear waste within Columbia River basalts

International Nuclear Information System (INIS)

Davis, J.D.

1982-01-01

Analysis of potential preclosure and postclosure disruptive events and processes is comprised of evaluation of (1) potential uncertainties and omissions associated with characterization of the site; (2) credible events and processes resulting from the dynamics of natural systems; (3) potential, credible changes in isolation conditions induced by the presence of the repository, and (4) potential, credible future changes impacting isolation capability resulting from man's activities, independent of repository construction/operation. This report presents the overall methodology for identification, classification and analysis of disruptive events based on Nuclear Regulatory Commission and Environmental Protection Agency guidelines proposed in drafts of 10 CFR 60 and 40 CFR 191. Potential credible disruptive events, processes, and conditions are considered with respect to whether they are anticipated or unanticipated, and determined to have reasonably foreseeable, very unlikely, or extremely unlikely probability of occurrence. 85 refs., 2 figs., 7 tabs

Patterns of change in early childhood aggressive-disruptive behavior: gender differences in predictions from early coercive and affectionate mother-child interactions.

Science.gov (United States)

McFadyen-Ketchum, S A; Bates, J E; Dodge, K A; Pettit, G S

1996-10-01

The present study focused on mother-child interaction predictors of initial levels and change in child aggressive and disruptive behavior at school from kindergarten to third grade. Aggression-disruption was measured via annual reports from teachers and peers. Ordinary least-squares regression was used to identify 8 separate child aggression trajectories, 4 for each gender: high initial levels with increases in aggression, high initial levels with decrease in aggression, low initial levels with increases in aggression, and low initial levels with decreases in aggression. Mother-child interaction measures of coercion and nonaffection collected prior to kindergarten were predictive of initial levels of aggression-disruption in kindergarten in both boys and girls. However, boys and girls differed in how coercion and nonaffection predicted change in aggression-disruption across elementary school years. For boys, high coercion and nonaffection were particularly associated with the high-increasing-aggression trajectory, but for girls, high levels of coercion and nonaffection were associated with the high-decreasing-aggression trajectory. This difference is discussed in the context of Patterson et al.'s coercion training theory, and the need for gender-specific theories of aggressive development is noted.

Disruption Physics and Mitigation on DIII-D

International Nuclear Information System (INIS)

Whyte, D.G.; Humphreys, D.A.; Kellman, A.G.

2005-01-01

The contributions of the DIII-D tokamak toward the understanding and control of disruptions are reviewed. Disruptions are found to be deterministic, and the underlying causes of disruption can therefore be predicted and avoided. With sufficiently rapid detection, possible damage from disruptions can be mitigated using an understanding of disruption phenomenology and plasma physics. Regimes of high β are readily available in DIII-D and provide access to relatively high energy density disruptions, despite DIII-D's moderate magnetic field and size. DIII-D, with all-graphite wall armor and wall conditioning between discharges, has proven highly resilient to the deleterious effects that disruptions can have on plasma operations. Simultaneously, exploitation and adaptation of DIII-D's extensive core and edge plasma diagnostic set have allowed for unique plasma measurements during disruptions. These measurements have tied into the development of several physical models used to understand aspects of disruptions, such as magnetohydrodynamic growth at the disruption onset, radiation energy balance through the thermal quench, and halo currents during the current quench. Based on this fundamental understanding, DIII-D has developed techniques to mitigate the harmful effects of disruptions by radiative dissipation of the plasma energy and extrapolated these techniques for possible use on larger devices like ITER

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

Science.gov (United States)

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

Formation of precise 2D Au particle arrays via thermally induced dewetting on pre-patterned substrates

Directory of Open Access Journals (Sweden)

Dong Wang

2011-06-01

Full Text Available The fabrication of precise 2D Au nanoparticle arrays over a large area is presented. The technique was based on pre-patterning of the substrate before the deposition of a thin Au film, and the creation of periodic particle arrays by subsequent dewetting induced by annealing. Two types of pre-patterned substrates were used: The first comprised an array of pyramidal pits and the second an array of circular holes. For the dewetting of Au films on the pyramidal pit substrate, the structural curvature-driven diffusion cooperates with capillarity-driven diffusion, resulting in the formation of precise 2D particle arrays for films within a structure dependent thickness-window. For the dewetting of Au films on the circular hole substrate, the periodic discontinuities in the films, induced by the deposition, can limit the diffusion paths and lead to the formation of one particle per individual separated region (holes or mesas between holes, and thus, result in the evolution of precise 2D particle arrays. The influence of the pre-patterned structures and the film thickness is analyzed and discussed. For both types of pre-patterned substrate, the Au film thickness had to be adjusted in a certain thickness-window in order to achieve the precise 2D particle arrays.

Formation of precise 2D Au particle arrays via thermally induced dewetting on pre-patterned substrates

Science.gov (United States)

Ji, Ran

2011-01-01

Summary The fabrication of precise 2D Au nanoparticle arrays over a large area is presented. The technique was based on pre-patterning of the substrate before the deposition of a thin Au film, and the creation of periodic particle arrays by subsequent dewetting induced by annealing. Two types of pre-patterned substrates were used: The first comprised an array of pyramidal pits and the second an array of circular holes. For the dewetting of Au films on the pyramidal pit substrate, the structural curvature-driven diffusion cooperates with capillarity-driven diffusion, resulting in the formation of precise 2D particle arrays for films within a structure dependent thickness-window. For the dewetting of Au films on the circular hole substrate, the periodic discontinuities in the films, induced by the deposition, can limit the diffusion paths and lead to the formation of one particle per individual separated region (holes or mesas between holes), and thus, result in the evolution of precise 2D particle arrays. The influence of the pre-patterned structures and the film thickness is analyzed and discussed. For both types of pre-patterned substrate, the Au film thickness had to be adjusted in a certain thickness-window in order to achieve the precise 2D particle arrays. PMID:21977445

Expression of ICAM-1 in blood-spinal cord barrier disruption and CNS radiation injury

International Nuclear Information System (INIS)

Nordal, R.A.; Li, Y.-Q.; Wong, C.S.

2003-01-01

Full text: Intercellular adhesion molecule-1 (ICAM-1) expression is increased following a number of CNS insults in association with blood-brain barrier (BBB) disruption. While disruption of ICAM-1 expression reduces injury in diverse pathologies ranging from trauma to ischemia, its role in CNS radiation injury is not understood. Adult rats received 0 to 22 Gy to a 1.6 cm length of the cervical spinal cord. Expression of ICAM-1 was studied using immunohistochemistry (IHC). Blood-spinal cord barrier (BSCB) disruption was detected by IHC for endogenous albumin and the BBB protein endothelial barrier antigen (EBA). To assess the role of ICAM-1 in the mechanisms of BSCB disruption, animals received IV injections of an ICAM-1-specific blocking antibody (IA-29) or vehicle control, and BSCB disruption was examined by albumin IHC. ICAM-1, albumin, and EBA staining areas were quantified by digital image analysis. ICAM-1 expression localized predominantly to endothelium in non-irradiated spinal cord sections. Some expression was also identified in astrocytes. ICAM-1 expression was increased in white matter, but not in grey matter following radiation. After 22 Gy, ICAM-1 protein increased at 24 hours, and increased again from baseline at 17-20 weeks. Induction was seen in both the total immunostained area, and in the number of ICAM-1 positive glia. A dose response was observed in ICAM-1 expression 20 weeks after 16-20 Gy. BSCB disruption also increased with doses 16-20 Gy at 20 weeks. Blocking ICAM-1 with IA-29 significantly decreased BSCB leakage of albumin at 24 hours (p=0.03). Regions with both increased ICAM-1 expression and BSCB disruption were identified in white matter. Thus the dose response and spatial distribution of increased ICAM-1 expression parallels that for BSCB disruption. These results are consistent with a role for increased ICAM-1 expression in radiation-induced BSCB disruption. The effect of blocking ICAM-1 with a neutralizing antibody suggests its

Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells.

Science.gov (United States)

Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M; Rice, Kenner C; Gannon, Brenda M; Fantegrossi, William E; Gonzalez, Carmen; Paule, Merle G; Ali, Syed F

2016-08-26

Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as "bath salts." These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5mM-2.5mM) for 24h. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5mM, with similar effects observed after MDPV exposures starting at 1mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1mM and disruption of the monolayer at 2.5mM. MDMA induced disruption of the endothelial monolayer from 1mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses ≥0.5mM without vacuole formation; at 2.5mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants alter monoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic. Published by Elsevier Ireland Ltd.

Magnetic field induced flow pattern reversal in a ferrofluidic Taylor-Couette system.

Science.gov (United States)

Altmeyer, Sebastian; Do, Younghae; Lai, Ying-Cheng

2015-12-21

We investigate the dynamics of ferrofluidic wavy vortex flows in the counter-rotating Taylor-Couette system, with a focus on wavy flows with a mixture of the dominant azimuthal modes. Without external magnetic field flows are stable and pro-grade with respect to the rotation of the inner cylinder. More complex behaviors can arise when an axial or a transverse magnetic field is applied. Depending on the direction and strength of the field, multi-stable wavy states and bifurcations can occur. We uncover the phenomenon of flow pattern reversal as the strength of the magnetic field is increased through a critical value. In between the regimes of pro-grade and retrograde flow rotations, standing waves with zero angular velocities can emerge. A striking finding is that, under a transverse magnetic field, a second reversal in the flow pattern direction can occur, where the flow pattern evolves into pro-grade rotation again from a retrograde state. Flow reversal is relevant to intriguing phenomena in nature such as geomagnetic reversal. Our results suggest that, in ferrofluids, flow pattern reversal can be induced by varying a magnetic field in a controlled manner, which can be realized in laboratory experiments with potential applications in the development of modern fluid devices.

Estrogens can disrupt amphibian mating behavior.

Directory of Open Access Journals (Sweden)

Frauke Hoffmann

Full Text Available The main component of classical contraceptives, 17α-ethinylestradiol (EE2, has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L, alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline.

Plasmalemmal Vesicle Associated Protein-1 (PV-1 is a marker of blood-brain barrier disruption in rodent models

Directory of Open Access Journals (Sweden)

Ali Zarina S

2008-02-01

Full Text Available Abstract Background Plasmalemmal vesicle associated protein-1 (PV-1 is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state. Results We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated. Conclusion Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.

Disruptive innovation as an entrepreneurial process

NARCIS (Netherlands)

Chandra, Y.; Yang, S.-J.S.; Singh, P.; Prajogo, D.; O'Neill, P.; Rahman, S.

2008-01-01

Research on conditions and causal mechanisms that influence disruptive innovation has been relatively unexplored in the extant research in disruptive innovation. By re-conceptualizing disruptive innovation as an entrepreneurial process at product, firm and industry levels, this paper draws on

Search and Disrupt

DEFF Research Database (Denmark)

Ørding Olsen, Anders

. However, incumbent sources engaged in capability reconfiguration to accommodate disruption improve search efforts in disruptive technologies. The paper concludes that the value of external sources is contingent on more than their knowledge. Specifically, interdependence of sources in search gives rise...... to influence from individual strategic interests on the outcomes. More generally, this points to the need for understanding the two-way influence of sources, rather than viewing external search as one-way knowledge accessing....

Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Bejoy, Julie; Song, Liqing; Zhou, Yi; Li, Yan

2018-04-01

Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.

Pursuing minimally disruptive medicine: disruption from illness and health care-related demands is correlated with patient capacity.

Science.gov (United States)

Boehmer, Kasey R; Shippee, Nathan D; Beebe, Timothy J; Montori, Victor M

2016-06-01

Chronic conditions burden patients with illness and treatments. We know little about the disruption of life by the work of dialysis in relation to the resources patients can mobilize, that is, their capacity, to deal with such demands. We sought to determine the disruption of life by dialysis and its relation to patient capacity to cope. We administered a survey to 137 patients on dialysis at an academic medical center. We captured disruption from illness and treatment, and physical, mental, personal, social, financial, and environmental aspects of patient capacity using validated scales. Covariates included number of prescriptions, hours spent on health care, existence of dependents, age, sex, and income level. On average, patients reported levels of capacity and disruption comparable to published levels. In multivariate regression models, limited physical, financial, and mental capacity were significantly associated with greater disruption. Patients in the top quartile of disruption had lower-than-expected physical, financial, and mental capacity. Our sample generally had capacity comparable to other populations and may be able to meet the demands imposed by treatment. Those with reduced physical, financial, and mental capacity reported higher disruption and represent a vulnerable group that may benefit from innovations in minimally disruptive medicine. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Characterization of 6,13-bis(triisopropylsilylethynyl) pentacene organic thin film transistors fabricated using pattern-induced confined structure

Energy Technology Data Exchange (ETDEWEB)

Kim, Kyohyeok; Kwon, Namyong [Sungkyunkwan University Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Chung, Ilsub, E-mail: ichung@skku.ac.kr [Sungkyunkwan University Advanced Institute of Nanotechnology, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); College of Information and Communication Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

2014-01-01

Bottom gate organic thin film transistors (OTFTs) were fabricated on polyethersulphone substrate using an ink jet printing method. 6,13-bis(triisopropylsilylethynyl) (TIPS) pentacene and poly-4-vinylphenol (PVP) were used as an active material and as a gate insulator, respectively. In an attempt to reduce the coffee stain effect, TIPS pentacene active layer was printed onto the pattern-induced confined structure (PICS) which had been obtained by orthogonally printing Ag electrodes on the pre-printed PVP layer. The resolution of Ag patterns was obtained by modifying the surface energy using UV irradiation and substrate temperature. The channel lengths of the aforementioned PICS OTFTs were in the range of 10 μm to 50 μm. The average mobility and on/off ratio of PICS OTFTs were 0.034 cm{sup 2}/Vs and 10{sup 3}, respectively. - Highlights: • Ink-jet printed bottom gate organic thin film transistor on plastic substrate • Ag lines orthogonally printed on pre-printed poly-4-vinylphenol lines • Pattern-induced confined structures obtained • UV irradiation affects the surface energy and the resolution of the Ag patterns.

Calculation of diffraction patterns associated with electron irradiation induced amorphization of CuTi

International Nuclear Information System (INIS)

Devanathan, R.; Meshii, M.; Sabochik, M.J.

1990-11-01

A new approach that uses the multislice method in conjunction with molecular dynamics simulations to study electron irradiation induced amorphisation is presented. Diffraction patterns were calculated for CuTi and found to be more sensitive than the pair correlation function to the structural changes preceding amorphisation. The results from this approach and from a study of long range order are presented. 16 refs., 8 figs

Disrupted day-night pattern of cardiovascular death in obstructive sleep apnea.

Science.gov (United States)

Martins, Emerson Ferreira; Martinez, Denis; da Silva, Fernando A Boeira Sabino; Sezerá, Lauren; da Rosa de Camargo, Rodrigo; Fiori, Cintia Zappe; Fuchs, Flávio Danni; Moraes, Ruy Silveira

2017-10-01

Obstructive sleep apnea (OSA) patients who suffer sudden cardiac death die predominantly during the night. We aimed to investigate whether all cardiovascular-related deaths display the same night-time peak as sudden cardiac death. Data from a large cohort of adults who underwent full-night polysomnography between 1985 and 2015 in a university-affiliated sleep clinic were analyzed. Time and cause of death of these patients and of persons from the general population were identified in death certificates from the State Health Secretariat. The day-night pattern of cardiovascular death was compared among groups of non-OSA, OSA (apnea-hypopnea index, AHI ≥5), CPAP users, and persons from the general population. Among 619 certificates, 160 cardiovascular-related deaths were identified. The time of death of the 142 persons with OSA was uniformly distributed over 24 h, with neither an identifiable peak nor a circadian pattern (Rayleigh test; P = 0.8); the same flat distribution was seen in those with purported CPAP use (n = 49). Non-OSA individuals presented a morning peak and a night nadir of deaths, clearer when analyzed in eight-hour intervals. The same pattern was observed in 92 836 certificates from the State general population, with cardiovascular deaths showing the expected morning peak, night nadir, and a significant circadian pattern (Rayleigh test; P < 0.001). In OSA patients, the distribution of cardiovascular-related deaths throughout the 24-h period is virtually flat, in contrast with the described nighttime peak of sudden cardiac death. OSA-related phenomena during nighttime might be blunting the mechanisms, arrhythmic or not, behind the morning peak of cardiovascular-related deaths. Copyright © 2017 Elsevier B.V. All rights reserved.

Fullerenol cytotoxicity in kidney cells is associated with cytoskeleton disruption, autophagic vacuole accumulation, and mitochondrial dysfunction

International Nuclear Information System (INIS)

Johnson-Lyles, Denise N.; Peifley, Kimberly; Lockett, Stephen; Neun, Barry W.; Hansen, Matthew; Clogston, Jeffrey; Stern, Stephan T.; McNeil, Scott E.

2010-01-01

Water soluble fullerenes, such as the hydroxylated fullerene, fullerenol (C 60 OH x ), are currently under development for diagnostic and therapeutic biomedical applications in the field of nanotechnology. These molecules have been shown to undergo urinary clearance, yet there is limited data available on their renal biocompatibility. Here we examine the biological responses of renal proximal tubule cells (LLC-PK1) exposed to fullerenol. Fullerenol was found to be cytotoxic in the millimolar range, with viability assessed by the sulforhodamine B and trypan blue assays. Fullerenol-induced cell death was associated with cytoskeleton disruption and autophagic vacuole accumulation. Interaction with the autophagy pathway was evaluated in vitro by Lysotracker Red dye uptake, LC3-II marker expression and TEM. Fullerenol treatment also resulted in coincident loss of cellular mitochondrial membrane potential and ATP depletion, as measured by the Mitotracker Red dye and the luciferin-luciferase assays, respectively. Fullerenol-induced ATP depletion and loss of mitochondrial potential were partially ameliorated by co-treatment with the autophagy inhibitor, 3-methyladenine. In vitro fullerenol treatment did not result in appreciable oxidative stress, as measured by lipid peroxide and glutathione content. Based on these data, it is hypothesized that cytoskeleton disruption may be an initiating event in fullerenol cytotoxicity, leading to subsequent autophagy dysfunction and loss of mitochondrial capacity. As nanoparticle-induced cytoskeleton disruption, autophagic vacuole accumulation and mitochondrial dysfunction are commonly reported in the literature, the proposed mechanism may be relevant for a variety of nanomaterials.

Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood-Brain Barrier Disruption during Japanese Encephalitis Virus Infection.

Science.gov (United States)

Li, Fang; Wang, Yueyun; Yu, Lan; Cao, Shengbo; Wang, Ke; Yuan, Jiaolong; Wang, Chong; Wang, Kunlun; Cui, Min; Fu, Zhen F

2015-05-01

Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate

Blood-brain barrier disruption in CCL2 transgenic mice during pertussis toxin-induced brain inflammation

DEFF Research Database (Denmark)

Schellenberg, Angela E; Buist, Richard; Del Bigio, Marc R

2012-01-01

infiltrate into the brain parenchyma following the administration of pertussis toxin (PTx). METHODS: This study uses contrast-enhanced magnetic resonance imaging (MRI) to quantify the extent of blood-brain barrier (BBB) disruption in this model pre- and post-PTx administration compared to wild type mice....... Contrast-enhanced MR images were obtained before and 1, 3, and 5 days after PTx injection in each animal. After the final imaging session fluorescent dextran tracers were administered intravenously to each mouse and brains were examined histologically for cellular infiltrates, BBB leakage and tight...... junction protein. RESULTS: BBB breakdown, defined as a disruption of both the endothelium and glia limitans, was found only in CCL2 transgenic mice following PTx administration seen on MR images as focal areas of contrast enhancement and histologically as dextrans leaking from blood vessels. No evidence...

Structured Literature Review of digital disruption literature

DEFF Research Database (Denmark)

Vesti, Helle; Rosenstand, Claus Andreas Foss; Gertsen, Frank

2018-01-01

Digital disruption is a term/phenomenon frequently appearing in innovation management literature. However, no academic consensus exists as to what it entails; conceptual nor theoretical. We use the SLR-method (Structured Literature Review) to investigate digital disruption literature. A SLR......-study conducted in 2017 revealed some useful information on how disruption and digital disruption literature has developed over a specific period. However, this study was less representative of papers addressing digital disruption; which is the in-depth subject of this paper. To accommodate this, we intend...... to conduct a similar SLR-study assembling a body literature having digital disruption as the only common denominator...

Mechanistic evaluation of endocrine disrupting chemicals

DEFF Research Database (Denmark)

Taxvig, Camilla

BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent for the ...... metabolising system using liver S9 mixtures or hepatic rat microsomes could be a convenient method for the incorporation of metabolic aspects into in vitro testing for endocrine disrupting effects.......BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent......, to be able to detect effects and predict mixture effects. In addition, a new hypothesis have emerge concerning a potential role of exposure to endocrine disrupting chemicals, and the development of obesity and obesity related diseases. AIM: This PhD project aimed to gain more information regarding...

Electromagnetic analysis on Korean Helium Cooled Ceramic Reflector (HCCR) TBM during plasma major disruption

International Nuclear Information System (INIS)

Lee, Youngmin; Ku, Duck Young; Ahn, Mu-Young; Cho, Seungyon; Park, Yi-Hyun; Lee, Dong Won

2015-01-01

Korean Helium Cooled Ceramic Reflector (HCCR) Test Blanket Module (TBM) will be installed at the #18 equatorial port of the Vaccum Vessel in order to test the feasibility of the breeding blanket performance for forthcoming fusion power plant in the ITER TBM Program. Since ITER tokamak contains Vaccum Vessel and set of electromagnetic coils, the TBM as well as other components is greatly influenced by magnetic field generated by these coils. By the electromagnetic (EM) fast transient events such as major disruption (MD), vertical displacement event (VDE) or magnet fast discharge (MFD) occurred in tokamak system, the eddy current can be induced eventually in the conducting components. As a result, the magnetic field and induced eddy current produce extremely huge EM load (force and moment) on the TBM. Therefore, EM load calculation is one of the most important analyses for optimized design of TBM. In this study, a 20-degree sector model for tokamak system including central solenoid (CS) coil, poloidal field (PF) coil, toroidal field (TF) coil, vaccum vessel, shield blankets and TBM set (TBM, TBM key, TBM shield, TBM frame) is prepared for analysis by ANSYS-EMAG tool. Concerning the installation location of the TBM, a major disruption scenario is particularly applied for fast transient analysis. The final goal of this study is to evaluate the EM load on HCCR TBM during plasma major disruption.

Electromagnetic analysis on Korean Helium Cooled Ceramic Reflector (HCCR) TBM during plasma major disruption

Energy Technology Data Exchange (ETDEWEB)

Lee, Youngmin, E-mail: ymlee@nfri.re.kr [National Fusion Research Institute, Daejeon (Korea, Republic of); Ku, Duck Young; Ahn, Mu-Young; Cho, Seungyon; Park, Yi-Hyun [National Fusion Research Institute, Daejeon (Korea, Republic of); Lee, Dong Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

Korean Helium Cooled Ceramic Reflector (HCCR) Test Blanket Module (TBM) will be installed at the #18 equatorial port of the Vaccum Vessel in order to test the feasibility of the breeding blanket performance for forthcoming fusion power plant in the ITER TBM Program. Since ITER tokamak contains Vaccum Vessel and set of electromagnetic coils, the TBM as well as other components is greatly influenced by magnetic field generated by these coils. By the electromagnetic (EM) fast transient events such as major disruption (MD), vertical displacement event (VDE) or magnet fast discharge (MFD) occurred in tokamak system, the eddy current can be induced eventually in the conducting components. As a result, the magnetic field and induced eddy current produce extremely huge EM load (force and moment) on the TBM. Therefore, EM load calculation is one of the most important analyses for optimized design of TBM. In this study, a 20-degree sector model for tokamak system including central solenoid (CS) coil, poloidal field (PF) coil, toroidal field (TF) coil, vaccum vessel, shield blankets and TBM set (TBM, TBM key, TBM shield, TBM frame) is prepared for analysis by ANSYS-EMAG tool. Concerning the installation location of the TBM, a major disruption scenario is particularly applied for fast transient analysis. The final goal of this study is to evaluate the EM load on HCCR TBM during plasma major disruption.

Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-alpha Release by Mononuclear Cells in Healthy Adults

NARCIS (Netherlands)

Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost

2016-01-01

OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,

Sleep disruption increases seizure susceptibility: Behavioral and EEG evaluation of an experimental model of sleep apnea.

Science.gov (United States)

Hrnčić, Dragan; Grubač, Željko; Rašić-Marković, Aleksandra; Šutulović, Nikola; Šušić, Veselinka; Bjekić-Macut, Jelica; Stanojlović, Olivera

2016-03-01

Sleep disruption accompanies sleep apnea as one of its major symptoms. Obstructive sleep apnea is particularly common in patients with refractory epilepsy, but causing factors underlying this are far from being resolved. Therefore, translational studies regarding this issue are important. Our aim was to investigate the effects of sleep disruption on seizure susceptibility of rats using experimental model of lindane-induced refractory seizures. Sleep disruption in male Wistar rats with implanted EEG electrodes was achieved by treadmill method (belt speed set on 0.02 m/s for working and 0.00 m/s for stop mode, respectively). Animals were assigned to experimental conditions lasting 6h: 1) sleep disruption (sleep interrupted, SI; 30s working and 90 s stop mode every 2 min; 180 cycles in total); 2) activity control (AC, 10 min working and 30 min stop mode, 9 cycles in total); 3) treadmill chamber control (TC, only stop mode). Afterwards, the animals were intraperitoneally treated with lindane (L, 4 mg/kg, SI+L, AC+L and TC+L groups) or dimethylsulfoxide (DMSO, SIc, ACc and TCc groups). Convulsive behavior was assessed by seizure incidence, latency time to first seizure, and its severity during 30 min after drug administration. Number and duration of ictal periods were determined in recorded EEGs. Incidence and severity of lindane-induced seizures were significantly increased, latency time significantly decreased in animals undergoing sleep disruption (SI+L group) compared with the animals from TC+L. Seizure latency was also significantly decreased in SI+L compared to AC+L groups. Number of ictal periods were increased and duration of it presented tendency to increase in SI+L comparing to AC+L. No convulsive signs were observed in TCc, ACc and SIc groups, as well as no ictal periods in EEG. These results indicate sleep disruption facilitates induction of epileptic activity in rodent model of lindane-epilepsy enabling translational research of this phenomenon. Copyright �

Overview of core disruptive accidents

International Nuclear Information System (INIS)

Marchaterre, J.F.

1977-01-01

An overview of the analysis of core-disruptive accidents is given. These analyses are for the purpose of understanding and predicting fast reactor behavior in severe low probability accident conditions, to establish the consequences of such conditions and to provide a basis for evaluating consequence limiting design features. The methods are used to analyze core-disruptive accidents from initiating event to complete core disruption, the effects of the accident on reactor structures and the resulting radiological consequences are described

Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection.

Science.gov (United States)

Petricoin, Emanuel F; Rajapaske, Vinodh; Herman, Eugene H; Arekani, Ali M; Ross, Sally; Johann, Donald; Knapton, Alan; Zhang, J; Hitt, Ben A; Conrads, Thomas P; Veenstra, Timothy D; Liotta, Lance A; Sistare, Frank D

2004-01-01

Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry which communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity based processes as cascades of reinforcing information percolate through the system and become reflected in changing proteomic information content of the circulation. Serum Proteomic Pattern Diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. While this approach has shown tremendous promise in early detection of cancers, detection of drug-induced toxicity may also be possible with this same technology. Analysis of serum from rat models of anthracycline and anthracenedione induced cardiotoxicity indicate the potential clinical utility of diagnostic proteomic patterns where low molecular weight peptides and protein fragments may have higher accuracy than traditional biomarkers of cardiotoxicity such as troponins. These fragments may one day be harvested by circulating nanoparticles designed to absorb, enrich and amplify the diagnostic biomarker repertoire generated even at the critical initial stages of toxicity.

Pheromone disruption of Argentine ant trail integrity

Science.gov (United States)

Suckling, D.M.; Peck, R.W.; Manning, L.M.; Stringer, L.D.; Cappadonna, J.; El-Sayed, A. M.

2008-01-01

Disruption of Argentine ant trail following and reduced ability to forage (measured by bait location success) was achieved after presentation of an oversupply of trail pheromone, (Z)-9-hexadecenal. Experiments tested single pheromone point sources and dispersion of a formulation in small field plots. Ant walking behavior was recorded and digitized by using video tracking, before and after presentation of trail pheromone. Ants showed changes in three parameters within seconds of treatment: (1) Ants on trails normally showed a unimodal frequency distribution of walking track angles, but this pattern disappeared after presentation of the trail pheromone; (2) ants showed initial high trail integrity on a range of untreated substrates from painted walls to wooden or concrete floors, but this was significantly reduced following presentation of a point source of pheromone; (3) the number of ants in the pheromone-treated area increased over time, as recruitment apparently exceeded departures. To test trail disruption in small outdoor plots, the trail pheromone was formulated with carnuba wax-coated quartz laboratory sand (1 g quartz sand/0.2 g wax/1 mg pheromone). The pheromone formulation, with a half-life of 30 h, was applied by rotary spreader at four rates (0, 2.5, 7.5, and 25 mg pheromone/m2) to 1- and 4-m2 plots in Volcanoes National Park, Hawaii. Ant counts at bait cards in treated plots were significantly reduced compared to controls on the day of treatment, and there was a significant reduction in ant foraging for 2 days. These results show that trail pheromone disruption of Argentine ants is possible, but a much more durable formulation is needed before nest-level impacts can be expected. ?? 2008 Springer Science+Business Media, LLC.

Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway

Directory of Open Access Journals (Sweden)

Ramesh Vijay

2012-05-01

Full Text Available Abstract Background Sleepiness and cognitive dysfunction are recognized as prominent consequences of sleep deprivation. Experimentally induced short-term sleep fragmentation, even in the absence of any reductions in total sleep duration, will lead to the emergence of excessive daytime sleepiness and cognitive impairments in humans. Tumor necrosis factor (TNF-α has important regulatory effects on sleep, and seems to play a role in the occurrence of excessive daytime sleepiness in children who have disrupted sleep as a result of obstructive sleep apnea, a condition associated with prominent sleep fragmentation. The aim of this study was to examine role of the TNF-α pathway after long-term sleep fragmentation in mice. Methods The effect of chronic sleep fragmentation during the sleep-predominant period on sleep architecture, sleep latency, cognitive function, behavior, and inflammatory markers was assessed in C57BL/6 J and in mice lacking the TNF-α receptor (double knockout mice. In addition, we also assessed the above parameters in C57BL/6 J mice after injection of a TNF-α neutralizing antibody. Results Mice subjected to chronic sleep fragmentation had preserved sleep duration, sleep state distribution, and cumulative delta frequency power, but also exhibited excessive sleepiness, altered cognitive abilities and mood correlates, reduced cyclic AMP response element-binding protein phosphorylation and transcriptional activity, and increased phosphodiesterase-4 expression, in the absence of AMP kinase-α phosphorylation and ATP changes. Selective increases in cortical expression of TNF-α primarily circumscribed to neurons emerged. Consequently, sleepiness and cognitive dysfunction were absent in TNF-α double receptor knockout mice subjected to sleep fragmentation, and similarly, treatment with a TNF-α neutralizing antibody abrogated sleep fragmentation-induced learning deficits and increases in sleep propensity. Conclusions Taken together

Disruption studies in ASDEX Upgrade

International Nuclear Information System (INIS)

Pautasso, G.

2002-01-01

Disruption generate large thermal and mechanical stresses on the tokamak components. For a future reactor disruptions have a significant impact on the design since all loading conditions must be analyzed in accordance with stricter design criteria (due to safety or difficult maintenance). Therefore the uncertainties affecting the predicted stresses must be reduced as much as possible with a more comprehensive set of measurements and analyses in this generation of experimental machines, and avoidance/ predictive methods must be developed further. The study of disruptions on ASDEX Upgrade is focused on these subjects, namely on: (1) understanding the physical mechanisms leading to this phenomenon and learning to avoid it or to predict its occurrence (with neural networks, for example) and to mitigate its effects; (2) analyzing the effects of disruptions on the machine to determine the functional dependence of the thermal and mechanical loads upon the discharge parameters. This allows to dimension or reinforce the machine components to withstand these loads and to extrapolate them to tokamaks still in the design phase; (3) learning to mitigate the consequence of disruptions. (author)

Tributyltin disrupts feeding and energy metabolism in the goldfish (Carassius auratus).

Science.gov (United States)

Zhang, Jiliang; Sun, Ping; Yang, Fan; Kong, Tao; Zhang, Ruichen

2016-06-01

Tributyltin (TBT) can induce obesogen response. However, little is known about the adverse effects of TBT on food intake and energy metabolism. The present study was designed to investigate the effects of TBT, at environmental concentrations of 2.44 and 24.4 ng/L (1 and 10 ng/L as Sn), on feeding and energy metabolism in goldfish (Carassius auratus). After exposure for 54 d, TBT increased the weight gain and food intake in fish. The patterns of brain neuropeptide genes expression were in line with potential orexigenic effects, with increased expression of neuropeptide Y and apelin, and decreased expression of pro-opiomelanocortin, ghrelin, cocaine and amphetamine-regulated transcript, and corticotropin-releasing factor. Interestingly, the energy metabolism indicators (oxygen consumption, ammonia exertion and swimming activity) and the serum thyroid hormones were all significantly increased at the 2.44 ng/L TBT group in fish. However, no changes of energy metabolism indicators or a decrease of thyroid hormones was found at the 24.4 ng/L TBT group, which indicated a complex disrupting effect on metabolism of TBT. In short, TBT can alter feeding and energy metabolism in fish, which might promote the obesogenic responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-α Release by Mononuclear Cells in Healthy Adults

NARCIS (Netherlands)

Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; Vos, de Alex F.; Vos, de Willem M.; Poll, van der Tom; Wiersinga, W.J.

2016-01-01

Objectives:Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,

Systemic lipopolysaccharide administration impairs retrieval of context-object discrimination, but not spatial, memory: Evidence for selective disruption of specific hippocampus-dependent memory functions during acute neuroinflammation.

Science.gov (United States)

Czerniawski, Jennifer; Miyashita, Teiko; Lewandowski, Gail; Guzowski, John F

2015-02-01

Neuroinflammation is implicated in impairments in neuronal function and cognition that arise with aging, trauma, and/or disease. Therefore, understanding the underlying basis of the effect of immune system activation on neural function could lead to therapies for treating cognitive decline. Although neuroinflammation is widely thought to preferentially impair hippocampus-dependent memory, data on the effects of cytokines on cognition are mixed. One possible explanation for these inconsistent results is that cytokines may disrupt specific neural processes underlying some forms of memory but not others. In an earlier study, we tested the effect of systemic administration of bacterial lipopolysaccharide (LPS) on retrieval of hippocampus-dependent context memory and neural circuit function in CA3 and CA1 (Czerniawski and Guzowski, 2014). Paralleling impairment in context discrimination memory, we observed changes in neural circuit function consistent with disrupted pattern separation function. In the current study we tested the hypothesis that acute neuroinflammation selectively disrupts memory retrieval in tasks requiring hippocampal pattern separation processes. Male Sprague-Dawley rats given LPS systemically prior to testing exhibited intact performance in tasks that do not require hippocampal pattern separation processes: novel object recognition and spatial memory in the water maze. By contrast, memory retrieval in a task thought to require hippocampal pattern separation, context-object discrimination, was strongly impaired in LPS-treated rats in the absence of any gross effects on exploratory activity or motivation. These data show that LPS administration does not impair memory retrieval in all hippocampus-dependent tasks, and support the hypothesis that acute neuroinflammation impairs context discrimination memory via disruption of pattern separation processes in hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

Directory of Open Access Journals (Sweden)

Irna Sufiawati

Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

Chronic disruptions of circadian sleep regulation induce specific proinflammatory responses in the rat colon

Czech Academy of Sciences Publication Activity Database

Polidarová, Lenka; Houdek, Pavel; Sumová, Alena

2017-01-01

Roč. 34, č. 9 (2017), s. 1273-1287 ISSN 0742-0528 R&D Projects: GA ČR(CZ) GA14-07711S Institutional support: RVO:67985823 Keywords : aging * colon * constant light * melatonin * proinflammatory cytokine * Rgs16 * sleep disruption Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 2.562, year: 2016

Disruptive event analysis: volcanism and igneous intrusion

International Nuclear Information System (INIS)

Crowe, B.M.

1979-01-01

Three basic topics are addressed for the disruptive event analysis: first, the range of disruptive consequences of a radioactive waste repository by volcanic activity; second, the possible reduction of the risk of disruption by volcanic activity through selective siting of a repository; and third, the quantification of the probability of repository disruption by volcanic activity

Routine Responses to Disruption of Routines

Science.gov (United States)

Guha, Mahua

2015-01-01

"Organisational routines" is a widely studied research area. However, there is a dearth of research on disruption of routines. The few studies on disruption of routines discussed problem-solving activities that are carried out in response to disruption. In contrast, this study develops a theory of "solution routines" that are a…

The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review.

Science.gov (United States)

Builee, T L; Hatherill, J R

2004-11-01

Thyroid hormones (TH) are essential to normal brain development, influencing behavior and cognitive function in both adult and children. It is suggested that conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral impulses found in cases of attention deficit hyperactivity disorder (ADHD) and other cognitive disorders. Disrupters of TH are various and prevalent in the environment. This paper reviews the mechanisms of TH disruption caused by the general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis, as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in accelerated clearance of TH. PHAHs can compromise function of transport and receptor binding proteins such as transthyretin and aryl hydrocarbon receptors (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain by the presence of PHAH. Further, PHAH can alter brain growth and development by perturbing cytoskeletal formation, thereby affecting neuronal migration, elongation and branching. The complex relationships between PHAH and cognitive function are examined in regard to the disruption of T4 regulation in the hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and postnatal development.

The disruption management model.

Science.gov (United States)

McAlister, James

2011-10-01

Within all organisations, business continuity disruptions present a set of dilemmas that managers may not have dealt with before in their normal daily duties. The disruption management model provides a simple but effective management tool to enable crisis management teams to stay focused on recovery in the midst of a business continuity incident. The model has four chronological primary headlines, which steer the team through a quick-time crisis decision-making process. The procedure facilitates timely, systematic, rationalised and justified decisions, which can withstand post-event scrutiny. The disruption management model has been thoroughly tested within an emergency services environment and is proven to significantly support clear and concise decision making in a business continuity context.

Sustainable Disruption Management

DEFF Research Database (Denmark)

Vaaben, Bo Valdemar

The world we live in is globalized. Goods are seldom made in the place where they are used or consumed, and we do increasingly travel to other countries for either business or pleasure. In our everyday lives we rely on well-functioning global transportations systems to continue the standard...... in the same way, when operation is disrupted. Never the less, we may recall that the Suez Canal was closed due to riots in Egypt, that the fuel price was impacted by threats of closing of the Strait of Hormuz, and we do from time to time hear about acts of piracy outside the coast of Somalia. All...... papers combining disruption management and flight planning through an integrated optimization approach. An additional contribution of the thesis is to show how flexible flight speeds can be used to improve recovery from disruptions, while at the same time allowing an airline to trade off fuel costs...

Disruption and Distinctiveness in Higher Education

Science.gov (United States)

Purcell, Wendy

2014-01-01

"Disruption"--while an evocative word triggering feelings of anxiety and perhaps even fear--also signals renewal and growth. The Higher Education (HE) sector in England has experienced some profound disruption over the years, and yet has emerged stronger and renewed in many ways. The impact of recent disruptive forces, from fees to the…

Resting potential, oncogene-induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo

Science.gov (United States)

Lobikin, Maria; Chernet, Brook; Lobo, Daniel; Levin, Michael

2012-12-01

Cancer may result from localized failure of instructive cues that normally orchestrate cell behaviors toward the patterning needs of the organism. Steady-state gradients of transmembrane voltage (Vmem) in non-neural cells are instructive, epigenetic signals that regulate pattern formation during embryogenesis and morphostatic repair. Here, we review molecular data on the role of bioelectric cues in cancer and present new findings in the Xenopus laevis model on how the microenvironment's biophysical properties contribute to cancer in vivo. First, we investigated the melanoma-like phenotype arising from serotonergic signaling by ‘instructor’ cells—a cell population that is able to induce a metastatic phenotype in normal melanocytes. We show that when these instructor cells are depolarized, blood vessel patterning is disrupted in addition to the metastatic phenotype induced in melanocytes. Surprisingly, very few instructor cells need to be depolarized for the hyperpigmentation phenotype to occur; we present a model of antagonistic signaling by serotonin receptors that explains the unusual all-or-none nature of this effect. In addition to the body-wide depolarization-induced metastatic phenotype, we investigated the bioelectrical properties of tumor-like structures induced by canonical oncogenes and cancer-causing compounds. Exposure to carcinogen 4-nitroquinoline 1-oxide (4NQO) induces localized tumors, but has a broad (and variable) effect on the bioelectric properties of the whole body. Tumors induced by oncogenes show aberrantly high sodium content, representing a non-invasive diagnostic modality. Importantly, depolarized transmembrane potential is not only a marker of cancer but is functionally instructive: susceptibility to oncogene-induced tumorigenesis is significantly reduced by forced prior expression of hyperpolarizing ion channels. Importantly, the same effect can be achieved by pharmacological manipulation of endogenous chloride channels, suggesting

BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L).

Science.gov (United States)

Maiuri, Maria Chiara; Criollo, Alfredo; Tasdemir, Ezgi; Vicencio, José Miguel; Tajeddine, Nicolas; Hickman, John A; Geneste, Olivier; Kroemer, Guido

2007-01-01

Beclin 1 has recently been identified as novel BH3-only protein, meaning that it carries one Bcl-2-homology-3 (BH3) domain. As other BH3-only proteins, Beclin 1 interacts with anti-apoptotic multidomain proteins of the Bcl-2 family (in particular Bcl-2 and its homologue Bcl-X(L)) by virtue of its BH3 domain, an amphipathic alpha-helix that binds to the hydrophobic cleft of Bcl-2/Bcl-X(L). The BH3 domains of other BH3-only proteins such as Bad, as well as BH3-mimetic compounds such as ABT737, competitively disrupt the inhibitory interaction between Beclin 1 and Bcl-2/Bcl-X(L). This causes autophagy of mitochondria (mitophagy) but not of the endoplasmic reticulum (reticulophagy). Only ER-targeted (not mitochondrion-targeted) Bcl-2/Bcl-X(L) can inhibit autophagy induced by Beclin 1, and only Beclin 1-Bcl-2/Bcl-X(L) complexes present in the ER (but not those present on heavy membrane fractions enriched in mitochondria) are disrupted by ABT737. These findings suggest that the Beclin 1-Bcl-2/Bcl-X(L) complexes that normally inhibit autophagy are specifically located in the ER and point to an organelle-specific regulation of autophagy. Furthermore, these data suggest a spatial organization of autophagy and apoptosis control in which BH3-only proteins exert two independent functions. On the one hand, they can induce apoptosis, by (directly or indirectly) activating the mitochondrion-permeabilizing function of pro-apoptotic multidomain proteins from the Bcl-2 family. On the other hand, they can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-X(L) at the level of the endoplasmic reticulum.

Neural-net disruption predictor in JT-60U

International Nuclear Information System (INIS)

Yoshino, R.

2003-01-01

The prediction of major disruptions caused by the density limit, the plasma current ramp-down with high internal inductance l i , the low density locked mode and the β-limit has been investigated in JT-60U. The concept of 'stability level', newly proposed in this paper to predict the occurrence of a major disruption, is calculated from nine input parameters every 2 ms by the neural network and the start of a major disruption is predicted when the stability level decreases to a certain level, the 'alarm level'. The neural network is trained in two steps. It is first trained with 12 disruptive and six non-disruptive shots (total of 8011 data points). Second, the target output data for 12 disruptive shots are modified and the network is trained again with additional data points generated by the operator. The 'neural-net disruption predictor' obtained has been tested for 300 disruptive shots (128 945 data points) and 1008 non-disruptive shots (982 800 data points) selected from nine years of operation (1991-1999) of JT-60U. Major disruptions except for those caused by the -limit have been predicted with a prediction success rate of 97-98% at 10 ms prior to the disruption and higher than 90% at 30 ms prior to the disruption while the false alarm rate is 2.1% for non-disruptive shots. This prediction performance has been confirmed for 120 disruptive shots (56 163 data points), caused by the density limit, as well as 1032 non-disruptive shots (1004 611 data points) in the last four years of operation (1999-2002) of JT-60U. A careful selection of the input parameters supplied to the network and the newly developed two-step training of the network have reduced the false alarm rate resulting in a considerable improvement of the prediction success rate. (author)

Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice.

Science.gov (United States)

Yuan, Jichao; Liu, Wei; Zhu, Haitao; Zhang, Xuan; Feng, Yang; Chen, Yaxing; Feng, Hua; Lin, Jiangkai

2017-01-01

Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery. Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice. We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Probabilistic analysis of tokamak plasma disruptions

International Nuclear Information System (INIS)

Sanzo, D.L.; Apostolakis, G.E.

1985-01-01

An approximate analytical solution to the heat conduction equations used in modeling component melting and vaporization resulting from plasma disruptions is presented. This solution is then used to propagate uncertainties in the input data characterizing disruptions, namely, energy density and disruption time, to obtain a probabilistic description of the output variables of interest, material melted and vaporized. (orig.)

Loss of aPKCλ in differentiated neurons disrupts the polarity complex but does not induce obvious neuronal loss or disorientation in mouse brains.

Directory of Open Access Journals (Sweden)

Tomoyuki Yamanaka

Full Text Available Cell polarity plays a critical role in neuronal differentiation during development of the central nervous system (CNS. Recent studies have established the significance of atypical protein kinase C (aPKC and its interacting partners, which include PAR-3, PAR-6 and Lgl, in regulating cell polarization during neuronal differentiation. However, their roles in neuronal maintenance after CNS development remain unclear. Here we performed conditional deletion of aPKCλ, a major aPKC isoform in the brain, in differentiated neurons of mice by camk2a-cre or synapsinI-cre mediated gene targeting. We found significant reduction of aPKCλ and total aPKCs in the adult mouse brains. The aPKCλ deletion also reduced PAR-6β, possibly by its destabilization, whereas expression of other related proteins such as PAR-3 and Lgl-1 was unaffected. Biochemical analyses suggested that a significant fraction of aPKCλ formed a protein complex with PAR-6β and Lgl-1 in the brain lysates, which was disrupted by the aPKCλ deletion. Notably, the aPKCλ deletion mice did not show apparent cell loss/degeneration in the brain. In addition, neuronal orientation/distribution seemed to be unaffected. Thus, despite the polarity complex disruption, neuronal deletion of aPKCλ does not induce obvious cell loss or disorientation in mouse brains after cell differentiation.

Stereoselective degradation and thyroid endocrine disruption of lambda-cyhalothrin in lizards (Eremias argus) following oral exposure.

Science.gov (United States)

Chang, Jing; Hao, Weiyu; Xu, Yuanyuan; Xu, Peng; Li, Wei; Li, Jianzhong; Wang, Huili

2018-01-01

The disturbance of the thyroid system and elimination of chiral pyrethroid pesticides with respect to enantioselectivity in reptiles have so far received limited attention by research. In this study, bioaccumulation, thyroid gland lesions, thyroid hormone levels, and hypothalamus-pituitary-thyroid axis-related gene expression in male Eremias argus were investigated after three weeks oral administration of lambda-cyhalothrin (LCT) enantiomers. In the lizard liver, the concentration of LCT was negatively correlated with the metabolite-3-phenoxybenzoic acid (PBA) level during 21 days of exposure. (+)-LCT exposure induced a higher thyroid follicular epithelium height than (-)-LCT exposure. The thyroxine levels were increased in both treated groups while only (+)-LCT exposure induced a significant change in the triiodothyronine (T3) level. In addition, the expressions of hypothalamus-pituitary-thyroid axis-related genes including thyroid hormone receptors (trs), deiodinases (dios), uridinediphosphate glucuronosyltransferase (udp), and sulfotransferase (sult) were up-regulated after exposure to the two enantiomers. (+)-LCT treatment resulted in higher expression of trs and (-)-LCT exposure led to greater stimulation of dios in the liver, which indicated PBA-induced antagonism on thyroid hormone receptors and LCT-induced disruption of thyroxine (T4) deiodination. The results suggest the (-)-LCT exposure causes higher residual level in lizard liver while induces less disruption on lizard thyroid activity than (+)-LCT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Plasma membrane disruption: repair, prevention, adaptation

Science.gov (United States)

McNeil, Paul L.; Steinhardt, Richard A.

2003-01-01

Many metazoan cells inhabit mechanically stressful environments and, consequently, their plasma membranes are frequently disrupted. Survival requires that the cell rapidly repair or reseal the disruption. Rapid resealing is an active and complex structural modification that employs endomembrane as its primary building block, and cytoskeletal and membrane fusion proteins as its catalysts. Endomembrane is delivered to the damaged plasma membrane through exocytosis, a ubiquitous Ca2+-triggered response to disruption. Tissue and cell level architecture prevent disruptions from occurring, either by shielding cells from damaging levels of force, or, when this is not possible, by promoting safe force transmission through the plasma membrane via protein-based cables and linkages. Prevention of disruption also can be a dynamic cell or tissue level adaptation triggered when a damaging level of mechanical stress is imposed. Disease results from failure of either the preventive or resealing mechanisms.

From Digital Disruption to Business Model Scalability

DEFF Research Database (Denmark)

Nielsen, Christian; Lund, Morten; Thomsen, Peter Poulsen

2017-01-01

This article discusses the terms disruption, digital disruption, business models and business model scalability. It illustrates how managers should be using these terms for the benefit of their business by developing business models capable of achieving exponentially increasing returns to scale...... will seldom lead to business model scalability capable of competing with digital disruption(s)....... as a response to digital disruption. A series of case studies illustrate that besides frequent existing messages in the business literature relating to the importance of creating agile businesses, both in growing and declining economies, as well as hard to copy value propositions or value propositions that take...

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

Energy Technology Data Exchange (ETDEWEB)

Tian, Shuangmei; Pan, Luqing, E-mail: panlq@ouc.edu.cn; Sun, Xiaohua

2013-11-15

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

An investigation of endocrine disrupting effects and toxic mechanisms modulated by benzo[a]pyrene in female scallop Chlamys farreri

International Nuclear Information System (INIS)

Tian, Shuangmei; Pan, Luqing; Sun, Xiaohua

2013-01-01

Highlights: •B[a]P disturbed progesterone, 17β-estradiol and testosterone production in scallop. •B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD expression after a 10-day exposure. •B[a]P of lower dose elevated AHR-CYP1A expression but high dose B[a]P inhibited them. •ER and vitellogenin transcription was consistent with AHR after B[a]P exposure. •B[a]P exposure induced relatively developmental delay and impairment of ovary. -- Abstract: The purpose of this study was to investigate the endocrine disrupting effects induced by benzo[a]pyrene (B[a]P) and explore the underlying mechanisms in mollusks. In this study, sexually mature female Chlamys farreri were exposed to benzo[a]pyrene for 10 days at four different concentrations as 0, 0.025, 0.5 and 10 μg/L. Sex steroids were identified and quantified by electrochemiluminescence immunoassay (ECLIA) method and results showed that exposure to B[a]P exerts great suppression on 17β-estradiol, testosterone production and disrupts progesterone levels in ovary. Transcription of genes were detected and measured by real-time RT-PCR. It showed that at day 10 B[a]P inhibited 3β-HSD, CYP17 and 17β-HSD mRNA expression in a dose-dependent manner, which suggests that they could be potential targets of B[a]P that disrupt steroidogenic machinery. Moreover, 0.025 μg/L B[a]P activated transcription of aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), CYP1A1 and estrogen receptor (ER), while 10 μg/L B[a]P suppressed all of them. The consistency of their responses to B[a]P exposure implies that AHR action may be involved in invertebrate CYP regulation and ER transcription despite of unknown mechanisms. Additionally, B[a]P exposure could induce ovarian impairment and developmental delay in C. farreri. Overall, sensitivity of C. farreri to endocrine disruption and toxicity suggests that C. farreri is a suitable species for study of endocrine-disrupting effects in marine invertebrates. This study will form a

A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.

Science.gov (United States)

Shibui, Tatsuro; Hara, Hiroyoshi

2017-09-01

Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017. © 2017 American Institute of Chemical Engineers.

Business Model as an Inducer of Disruptive Innovations: The Case of Gol Airlines

OpenAIRE

Pereira, Sirlei de Almeida; Imbrizi, Fabricio Garcia; de Freitas, Alessandra Demite Goncalves; Alvarenga, Marcelo Aparecido

2015-01-01

This study was undertaken to investigate the premises that the success of disruptive innovation is related to the business model adopted by organizations. An analysis of five business models from the literature review - Bovet and Martha (2000), Applegate (2001), Chesbrough and Rosenbloom (2002), Osterwalder and Pigneur (2010), and Rodrigues, Maccari and Lenzi (2012) – was conducted based on the case of the Brazilian Gol Airlines who is recognized as a success business that promoted a disrupti...

β limit disruptions in the TFTR tokamak

International Nuclear Information System (INIS)

Fredrickson, E.D.; McGuire, K.; Janos, A.; Bell, M.; Budny, R.V.; Bush, C.E.; Manickam, J.; Mynick, H.; Nazikian, R.; Taylor, G.

1994-11-01

A disruptive β limit (β = plasma pressure/magnetic pressure) is observed in high performance plasmas in TFTR. The MHD character of these disruptions differs substantially from the disruptions in high density plasmas (density limit disruptions) on TFTR. The high β disruptions can occur with less than a milliseconds warning in the form of a fast growing precursor. The precursor appears to be an external kink or internal (m,n)=(1,1) kink strongly coupled through finite β effects and toroidal terms to higher m components. It does not have the open-quote cold bubble close-quote structure found in density limit disruptions. There is also no evidence for a change in the internal inductance, i.e., a major reconnection of the flux, at the time of the thermal quench

BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

Science.gov (United States)

Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

2014-05-01

Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

3rd Annual Disruptive Technology Conference

Science.gov (United States)

2006-09-07

Panel -- The Warfighter’s Perspective The Impact of Disruptive Technologies on Joint Warfighting MG Michael Vane, USA, Vice Director for Force...Structure, Resources & Assessment, Joint Staff, J-8 Panel -- Perspectives of Change: Identifying the Emerging Commercial Disruptive Technologies Decision...Mark Lucas, Board Member OSGeo, RadiantBlue Technologies Panel -- The Search for Disruptive Technologies - a “Blue Force” Multiplier Advanced

Reconstruction of Laser-Induced Surface Topography from Electron Backscatter Diffraction Patterns.

Science.gov (United States)

Callahan, Patrick G; Echlin, McLean P; Pollock, Tresa M; De Graef, Marc

2017-08-01

We demonstrate that the surface topography of a sample can be reconstructed from electron backscatter diffraction (EBSD) patterns collected with a commercial EBSD system. This technique combines the location of the maximum background intensity with a correction from Monte Carlo simulations to determine the local surface normals at each point in an EBSD scan. A surface height map is then reconstructed from the local surface normals. In this study, a Ni sample was machined with a femtosecond laser, which causes the formation of a laser-induced periodic surface structure (LIPSS). The topography of the LIPSS was analyzed using atomic force microscopy (AFM) and reconstructions from EBSD patterns collected at 5 and 20 kV. The LIPSS consisted of a combination of low frequency waviness due to curtaining and high frequency ridges. The morphology of the reconstructed low frequency waviness and high frequency ridges matched the AFM data. The reconstruction technique does not require any modification to existing EBSD systems and so can be particularly useful for measuring topography and its evolution during in situ experiments.

Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

Directory of Open Access Journals (Sweden)

Magdalena M Przybycien-Szymanska

2011-04-01

Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

Analysis of the direction of plasma vertical movement during major disruptions in ITER

International Nuclear Information System (INIS)

Lukash, Victor; Sugihara, Masayoshi; Gribov, Yuri; Fujieda, Hirobumi

2005-01-01

The plasma movement in the upward direction (away from the X-point) after the thermal quench (TQ) of major disruptions in ITER is favourable for the machine design, since the downward movement causes larger electromagnetic (EM) load due to the induced eddy and halo currents. Vertical directions of plasma movement after the TQ in ITER are investigated using the predictive mode of the DINA code. Three dominant parameters in determining the direction of plasma movement are identified: (i) the rate of plasma current quench (plasma temperature after the TQ) (ii) the width of plasma current mixing area just after the TQ (change of the internal plasma inductance l i ) and (iii) the initial vertical position of plasma column before the TQ. It is shown that the reference ITER plasma moves upwards after the TQ, if the electron temperature after the TQ is less than 10 eV and the drop of l i does not exceed 0.2 for the present reference initial vertical position (55.5 cm above the centre of the machine). It is also shown that the operational domain leading to the upward movement is considerably large for disruptions with fast current quench, which could generate quite severe EM load due to the induced eddy current combined with the induced halo current if the movement is downwards

Clerodendrum inerme Leaf Extract Alleviates Animal Behaviors, Hyperlocomotion, and Prepulse Inhibition Disruptions, Mimicking Tourette Syndrome and Schizophrenia

Directory of Open Access Journals (Sweden)

Hon-Lie Chen

2012-01-01

Full Text Available Previously, we found a patient with intractable motor tic disorder, a spectrum of Tourette syndrome (TS, responsive to the ground leaf juice of Clerodendrum inerme (CI. Here, we examined the effect of the ethanol extract of CI leaves (CI extract on animal behaviors mimicking TS, hyperlocomotion, and sensorimotor gating deficit. The latter is also observed in schizophrenic patients and can be reflected by a disruption of prepulse inhibition of acoustic startle response (PPI in animal models induced by methamphetamine and NMDA channel blockers (ketamine or MK-801, based on hyperdopaminergic and hypoglutamatergic hypotheses, respectively. CI extract (10–300 mg/kg, i.p. dose-dependently inhibited hyperlocomotion induced by methamphetamine (2 mg/kg, i.p. and PPI disruptions induced by methamphetamine, ketamine (30 mg/kg, i.p., and MK-801 (0.3 mg/kg, i.p. but did not affect spontaneous locomotor activity, rotarod performance, and grip force. These results suggest that CI extract can relieve hyperlocomotion and improve sensorimotor gating deficit, supporting the therapeutic potential of CI for TS and schizophrenia.

Dysphagia and disrupted cranial nerve development in a mouse model of DiGeorge (22q11 deletion syndrome

Directory of Open Access Journals (Sweden)

Beverly A. Karpinski

2014-02-01

Full Text Available We assessed feeding-related developmental anomalies in the LgDel mouse model of chromosome 22q11 deletion syndrome (22q11DS, a common developmental disorder that frequently includes perinatal dysphagia – debilitating feeding, swallowing and nutrition difficulties from birth onward – within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered expression and patterning of hindbrain transcriptional regulators, especially those related to retinoic acid (RA signaling, prefigures these disruptions. Subsequently, gene expression, axon growth and sensory ganglion formation in the trigeminal (V, glossopharyngeal (IX or vagus (X cranial nerves (CNs that innervate targets essential for feeding, swallowing and digestion are disrupted. Posterior CN IX and X ganglia anomalies primarily reflect diminished dosage of the 22q11DS candidate gene Tbx1. Genetic modification of RA signaling in LgDel embryos rescues the anterior CN V phenotype and returns expression levels or pattern of RA-sensitive genes to those in wild-type embryos. Thus, diminished 22q11 gene dosage, including but not limited to Tbx1, disrupts oro-facial and CN development by modifying RA-modulated anterior-posterior hindbrain differentiation. These disruptions likely contribute to dysphagia in infants and young children with 22q11DS.

Guanidinium-induced denaturation by breaking of salt bridges

NARCIS (Netherlands)

Meuzelaar, H.; Panman, M.R.; Woutersen, S.

2015-01-01

Despite its wide use as a denaturant, the mechanism by which guanidinium (Gdm+) induces protein unfolding remains largely unclear. Herein, we show evidence that Gdm+ can induce denaturation by disrupting salt bridges that stabilize the folded conformation. We study the Gdm+-​induced denaturation of

The Effects of Disruption on Strategic Management

DEFF Research Database (Denmark)

Drejer, Anders

2017-01-01

There is a lot of interest in Disruption these days even though the concept itself is still under formation. Disruption can be traced back to the idea of disruptive technological change and the late 1990s but has reemerged in the public eye in current years under guises such as Big Data......, Digitalization, Globalization and much more. Furthermore, the effects of disruption are now being felt by organizations and industries all over the world. In this paper, we will try to outline and illustrate some of those effects using the case-study of an international, Danish, SME. The case company has been...... forced to face some challenges caused by disruption and in the process of doing so has changed its strategy process significantly towards a more learning based approach to strategic management. Keywords: disruption; case- study; SME; strategy process....

Simulations of ITER disruption and VDE scenarios with TSC and comparison with DINA results

International Nuclear Information System (INIS)

Bandyopadhyay, I.

2008-01-01

Vertical Displacement Events (VDEs) and plasma current disruptions pose one of the major concerns for the lifetime of in-vessel components in ITER, as well as for machine robustness, as large electromagnetic and thermal loads will induced at such events. Hence, accurate modelling of such events is crucial for estimating disruption induced forces. In the past, ITER disruption modelling has been carried out for ITER using the DINA code. However, since predictive simulations of such events depend on a large number of model assumptions, there exists chances of large error bars on the model predictions. As such it is imperative to validate the code results with other models. Towards this objective, we have carried out the VDE and Disruption simulations using the TSC code and the results are compared with the earlier DINA predictions. A detailed electromagnetic model of the ITER vessel, blankets and the first wall components has been created in TSC. In both VDE and disruption cases, the initial plasma is taken as ITER reference scenario 2 end of burn (EOB) specifications with I p = 15 MA, B t = 5 .3 T, e > 8.8 keV, e > = 1.1 x 10 20 m -3 . The plasma current disruption is initiated by dropping the plasma β in 1 msec, so that after the β crash e > = 6 eV, following which the plasma position control is switched off, resulting in a plasma current quench in about 65 msec. On the other hand, in the VDE case, the plasma control is switched off which results in either upward or downward VDE depending on the initial position of the plasma current centroid. In this case the plasma current remains close to 15 MA for a much longer time, about 700 msec in the simulations till the edge safety factor (q) becomes less than 1.5, following which the β is crashed resulting in plasma current quench. Significant differences exist in the DINA and TSC models, for example, even though the plasma current quench rate predicted by the models matches well in till the halo currents start flowing

Disruption of an Alumina Layer During Sintering of Aluminium in Nitrogen

Directory of Open Access Journals (Sweden)

Pieczonka T.

2017-06-01

Full Text Available Aluminium oxide layer on aluminium particles cannot be avoided. However, to make the metal-metal contacts possible, this sintering barrier has to be overcome in some way, necessarily to form sintering necks and their development. It is postulated that the disruption of alumina layer under sintering conditions may originate physically and chemically. Additionally, to sinter successfully non alloyed aluminium powder in nitrogen, the operation of both types mechanism is required. It is to be noted that metallic aluminium surface has to be available to initiate reactions between aluminium and the sintering atmosphere, i.e. mechanical disruption of alumina film precedes the chemical reactions, and only then chemically induced mechanisms may develop. Dilatometry, gravimetric and differential thermal analyses, and microstructure investigations were used to study the sintering response of aluminium at 620°C in nitrogen, which is the only sintering atmosphere producing shrinkage.

Fluoride-induced disruption of reproductive hormones in men

International Nuclear Information System (INIS)

Ortiz-Perez, Deogracias; Rodriguez-Martinez, Manuel; Martinez, Flavio; Borja-Aburto, V.H.; Castelo, Julio; Grimaldo, J.I.; Cruz, Esperanza de la; Carrizales, Leticia; Diaz-Barriga, Fernando

2003-01-01

Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group--HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs

Forearm interosseous membrane trauma: MRI diagnostic criteria and injury patterns

Energy Technology Data Exchange (ETDEWEB)

McGinley, Joseph C. [Stanford University Medical Center, Department of Radiology, Stanford, CA (United States); Roach, Neil [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Hopgood, Brendon C. [Albert Einstein Medical Center, Department of Surgery, Philadelphia, PA (United States); Limmer, Karl [Temple University School of Medicine, Philadelphia, PA (United States); Kozin, Scott H. [Shriners Hospital for Children, Temple University and Pediatric Hand and Upper Extremity Surgeon, Philadelphia, PA (United States)

2006-05-15

Define criteria for interosseous membrane (IOM) injury diagnosis using MRI, and characterize patterns of IOM disruption following forearm trauma. Our hypothesis is that most IOM injuries occur along the ulnar insertion, and MRI should be obtained following forearm trauma to assess IOM competency. Sixteen cadaver forearms were subjected to longitudinal impact trauma. Prior to and following injury, MR images were examined by a board-certified musculoskeletal radiologist using pre-defined criteria for determining IOM integrity. Each specimen was dissected and the viability/pattern of injury examined. The MRI and dissection results were compared using a double-blinded methodology. Eight of the 16 specimens demonstrated IOM trauma. Seven specimens demonstrated complete IOM disruption from the ulnar insertion, and one revealed a mid-substance tear with intact origin and insertion. The dorsal oblique bundle was disrupted in four specimens. MRI analysis identified IOM injury in seven of the eight forearms. The injury location was correctly identified in six specimens when compared to dissection observations. MRI determination of IOM injury demonstrated a positive predictive value of 100%, a negative predictive value of 89%, a sensitivity of 87.5% and a specificity of 100%. (orig.)

Forearm interosseous membrane trauma: MRI diagnostic criteria and injury patterns

International Nuclear Information System (INIS)

McGinley, Joseph C.; Roach, Neil; Hopgood, Brendon C.; Limmer, Karl; Kozin, Scott H.

2006-01-01

Define criteria for interosseous membrane (IOM) injury diagnosis using MRI, and characterize patterns of IOM disruption following forearm trauma. Our hypothesis is that most IOM injuries occur along the ulnar insertion, and MRI should be obtained following forearm trauma to assess IOM competency. Sixteen cadaver forearms were subjected to longitudinal impact trauma. Prior to and following injury, MR images were examined by a board-certified musculoskeletal radiologist using pre-defined criteria for determining IOM integrity. Each specimen was dissected and the viability/pattern of injury examined. The MRI and dissection results were compared using a double-blinded methodology. Eight of the 16 specimens demonstrated IOM trauma. Seven specimens demonstrated complete IOM disruption from the ulnar insertion, and one revealed a mid-substance tear with intact origin and insertion. The dorsal oblique bundle was disrupted in four specimens. MRI analysis identified IOM injury in seven of the eight forearms. The injury location was correctly identified in six specimens when compared to dissection observations. MRI determination of IOM injury demonstrated a positive predictive value of 100%, a negative predictive value of 89%, a sensitivity of 87.5% and a specificity of 100%. (orig.)

Valproic acid disrupts the oscillatory expression of core circadian rhythm transcription factors.

Science.gov (United States)

Griggs, Chanel A; Malm, Scott W; Jaime-Frias, Rosa; Smith, Catharine L

2018-01-15

Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop. In cells with an unsynchronized clock, VPA simultaneously upregulated the expression of genes encoding core circadian transcription factors that regulate the positive and negative limbs of the feedback loop. Using low dose glucocorticoid, we synchronized cultured fibroblast cells to a circadian oscillatory pattern. Whether VPA was added at the time of synchronization or 12h later at CT12, we found that VPA disrupted the oscillatory expression of multiple genes encoding essential transcription factors that regulate circadian rhythm. Therefore, we conclude that VPA has a potent effect on the circadian rhythm transcription-translation feedback loop that may be linked to negative VPA side effects in humans. Furthermore, our study suggests potential chronopharmacology implications of VPA usage. Copyright © 2017. Published by Elsevier Inc.

Assessing urban context-induced change in individual activity travel patterns : case study of new railway station

NARCIS (Netherlands)

Arentze, T.A.; Borgers, A.W.J.; Ponjé, M.M.W.; Stams, A.; Timmermans, H.J.P.

2001-01-01

Findings are reported of selective descriptive analyses that were conducted to examine whether the opening of a new railway station had induced any changes in the activity travel patterns of a panel of house holds. In particular, changes in choices related to trip generation, trip chaining,

Minocycline Attenuates Iron-Induced Brain Injury.

Science.gov (United States)

Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

2016-01-01

Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

Directory of Open Access Journals (Sweden)

Min-Hsuan Lin

Full Text Available Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1, nucleophosmin (B23 and nucleolin (C23 from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.

Apnea-induced rapid eye movement sleep disruption impairs human spatial navigational memory.

Science.gov (United States)

Varga, Andrew W; Kishi, Akifumi; Mantua, Janna; Lim, Jason; Koushyk, Viachaslau; Leibert, David P; Osorio, Ricardo S; Rapoport, David M; Ayappa, Indu

2014-10-29

Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA. Copyright © 2014 the authors 0270-6474/14/3414571-07$15.00/0.

Towards a Framework of Digital Platform Disruption

DEFF Research Database (Denmark)

Kazan, Erol; Tan, Chee-Wee; Lim, Eric T. K.

2014-01-01

Digital platforms are disruptive information technology (IT) artifacts that erode conventional business logic associated with traditional market structures. This paper presents a framework for examining the disruptive potential of digital platforms whereby we postulate that the strategic interplay...... digital platforms purposely decouple platform layers, to foster open innovation and accelerate market disruption. This paper therefore represents a first concrete step aimed at unravelling the disruptive potential of digital platforms....... of governance regimes and platform layers is deterministic of whether disruptive derivatives are permitted to flourish. This framework has been employed in a comparative case study between centralized (i.e., PayPal) and decentralized (i.e., Coinkite) digital payment platforms to illustrate its applicability...

Real-time disruption handling at ASDEX upgrade

International Nuclear Information System (INIS)

Zehetbauer, Th.; Pautasso, G.; Tichmann, C.; Egorov, S.; Lorenz, A.; Mertens, V.; Neu, G.; Raupp, G.; Treutterer, W.; Zasche, D.

2001-01-01

A neural network for prediction of disruptions has been developed at ASDEX Upgrade with the goal to mitigate or avoid these. The novel idea is to compute the remaining time-to-disruption to indicate the stability level of the discharge. The neural network has been specified, trained and then implemented within the real-time plasma control system. The current version of the system terminates the discharge with an impurity pellet when the computed time-to-disruption falls below a threshold of 80 ms. Routine operation shows that disruptions are recognized reliably. Vessel currents and forces are considerably reduced. The system will be enhanced to avoid disruptions with a soft landing initiated in time

Family Disruptions

Science.gov (United States)

... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Disruptions Page Content Article Body No matter how ...

Field effect transistors and photodetectors based on nanocrystalline graphene derived from electron beam induced carbonaceous patterns

International Nuclear Information System (INIS)

Kurra, Narendra; Bhadram, Venkata Srinu; Narayana, Chandrabhas; Kulkarni, G U

2012-01-01

We describe a transfer-free method for the fabrication of nanocrystalline graphene (nc-graphene) on SiO 2 substrates directly from patterned carbonaceous deposits. The deposits were produced from the residual hydrocarbons present in the vacuum chamber without any external source by using an electron beam induced carbonaceous deposition (EBICD) process. Thermal treatment under vacuum conditions in the presence of Ni catalyst transformed the EBIC deposit into nc-graphene patterns, confirmed using Raman and TEM analysis. The nc-graphene patterns have been employed as an active p-type channel material in a field effect transistor (FET) which showed a hole mobility of ∼90 cm 2 V −1 s −1 . The nc-graphene also proved to be suitable material for IR detection. (paper)

Direct-write maskless lithography using patterned oxidation of Si-substrate Induced by femtosecond laser pulses

Science.gov (United States)

Kiani, Amirkianoosh; Venkatakrishnan, Krishnan; Tan, Bo

2013-03-01

In this study we report a new method for direct-write maskless lithography using oxidized silicon layer induced by high repetition (MHz) ultrafast (femtosecond) laser pulses under ambient condition. The induced thin layer of predetermined pattern can act as an etch stop during etching process in alkaline etchants such as KOH. The proposed method can be leading to promising solutions for direct-write maskless lithography technique since the proposed method offers a higher degree of flexibility and reduced time and cost of fabrication which makes it particularly appropriate for rapid prototyping and custom scale manufacturing. A Scanning Electron Microscope (SEM), Micro-Raman, Energy Dispersive X-ray (EDX), optical microscope and X-ray diffraction spectroscopy (XRD) were used to evaluate the quality of oxidized layer induced by laser pulses.

Atmospheric-pressure guided streamers for liposomal membrane disruption

International Nuclear Information System (INIS)

Svarnas, P.; Aleiferis, Sp.; Matrali, S. H.; Gazeli, K.; Clément, F.; Antimisiaris, S. G.

2012-01-01

The potential to use liposomes (LIPs) as a cellular model in order to study interactions of cold atmospheric-pressure plasma with cells is herein investigated. Cold atmospheric-pressure plasma is formed by a dielectric-barrier discharge reactor. Large multilamellar vesicle liposomes, consisted of phosphatidylcholine and cholesterol, are prepared by the thin film hydration technique, to encapsulate a small hydrophilic dye, i.e., calcein. The plasma-induced release of calcein from liposomes is then used as a measure of liposome membrane integrity and, consequently, interaction between the cold atmospheric plasma and lipid bilayers. Physical mechanisms leading to membrane disruption are suggested, based on the plasma characterization including gas temperature calculation.

Disruption modeling in support of ITER

International Nuclear Information System (INIS)

Bandyopadhyay, I.

2015-01-01

Plasma current disruptions and Vertical Displacement Events (VDEs) are one of the major concerns in any tokamak as they lead to large electromagnetic forces to tokamak first wall components and vacuum vessel. Their occurrence also means disruption to steady state operations of tokamaks. Thus future fusion reactors like ITER must ensure that disruptions and VDEs are minimized. However, since there is still finite probability of their occurrence, one must be able to characterize disruptions and VDEs and able to predict, for example, the plasma current quench time and halo current amplitude, which mainly determine the magnitude of the electromagnetic forces. There is a concerted effort globally to understand and predict plasma and halo current evolution during disruption in tokamaks through MHD simulations. Even though Disruption and VDEs are often 3D MHD perturbations in nature, presently they are mostly simulated using 2D axisymmetric MHD codes like the Tokamak Simulation Code (TSC) and DINA. These codes are also extensively benchmarked against experimental data in present day tokamaks to improve these models and their ability to predict these events in ITER. More detailed 3D models like M3D are only recently being developed, but they are yet to be benchmarked against experiments, as also they are massively computationally exhaustive

Disrupted Disclosure

DEFF Research Database (Denmark)

Krause Hansen, Hans; Uldam, Julie

appearances become challenged through disruptive disclosures in mediaenvironments characterized by multiple levels of visibility, with companies both observing andbeing observed by civil society groups that criticize them; (c) why and how the mobilization aroundtransparency and ensuing practices...

Pixelated camouflage patterns from the perspective of hyperspectral imaging

Science.gov (United States)

Racek, František; Jobánek, Adam; Baláž, Teodor; Krejčí, Jaroslav

2016-10-01

Pixelated camouflage patterns fulfill the role of both principles the matching and the disrupting that are exploited for blending the target into the background. It means that pixelated pattern should respect natural background in spectral and spatial characteristics embodied in micro and macro patterns. The HS imaging plays the similar, however the reverse role in the field of reconnaissance systems. The HS camera fundamentally records and extracts both the spectral and spatial information belonging to the recorded scenery. Therefore, the article deals with problems of hyperspectral (HS) imaging and subsequent processing of HS images of pixelated camouflage patterns which are among others characterized by their specific spatial frequency heterogeneity.

MHD stability, operational limits and disruptions

International Nuclear Information System (INIS)

1999-01-01

The present physics understandings of magnetohydrodynamic (MHD) stability of tokamak plasmas, the threshold conditions for onset of MHD instability, and the resulting operational limits on attainable plasma pressure (beta limit) and density (density limit), and the consequences of plasma disruption and disruption related effects are reviewed and assessed in the context of their application to a future DT burning reactor prototype tokamak experiment such as ITER. The principal considerations covered within the MHD stability and beta limit assessments are (i) magnetostatic equilibrium, ideal MHD stability and the resulting ideal MHD beta limit; (ii) sawtooth oscillations and the coupling of sawtooth activity to other types of MHD instability; (iii) neoclassical island resistive tearing modes and the corresponding limits on beta and energy confinement; (iv) wall stabilization of ideal MHD instabilities and resistive wall instabilities; (v) mode locking effects of non-axisymmetric error fields; (vi) edge localized MHD instabilities (ELMs, etc.); and (vii) MHD instabilities and beta/pressure gradient limits in plasmas with actively modified current and magnetic shear profiles. The principal considerations covered within the density limit assessments are (i) empirical density limits; (ii) edge power balance/radiative density limits in ohmic and L-mode plasmas; and (iii) edge parameter related density limits in H-mode plasmas. The principal considerations covered in the disruption assessments are (i) disruption causes, frequency and MHD instability onset; (ii) disruption thermal and current quench characteristics; (iii) vertical instabilities (VDEs), both before and after disruption, and plasma and in-vessel halo currents; (iv) after disruption runaway electron formation, confinement and loss; (v) fast plasma shutdown (rapid externally initiated dissipation of plasma thermal and magnetic energies); (vi) means for disruption avoidance and disruption effect mitigation; and

Chronic stress disrupts neural coherence between cortico-limbic structures

Directory of Open Access Journals (Sweden)

João Filipe Oliveira

2013-02-01

Full Text Available Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP and the medial prefrontal cortex (mPFC in rats subjected to short term (STS and chronic unpredictable stress (CUS. CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

Current research on methamphetamine-induced neurotoxicity: animal models of monoamine disruption.

Science.gov (United States)

Kita, Taizo; Wagner, George C; Nakashima, Toshikatsu

2003-07-01

Methamphetamine (METH)-induced neurotoxicity is characterized by a long-lasting depletion of striatal dopamine (DA) and serotonin as well as damage to striatal dopaminergic and serotonergic nerve terminals. Several hypotheses regarding the mechanism underlying METH-induced neurotoxicity have been proposed. In particular, it is thought that endogenous DA in the striatum may play an important role in mediating METH-induced neuronal damage. This hypothesis is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of DA consequent to its displacement from synaptic vesicles to cytoplasm. In addition, METH-induced neurotoxicity may be linked to the glutamate and nitric oxide systems within the striatum. Moreover, using knockout mice lacking the DA transporter, the vesicular monoamine transporter 2, c-fos, or nitric oxide synthetase, it was determined that these factors may be connected in some way to METH-induced neurotoxicity. Finally a role for apoptosis in METH-induced neurotoxicity has also been established including evidence of protection of bcl-2, expression of p53 protein, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), activity of caspase-3. The neuronal damage induced by METH may reflect neurological disorders such as autism and Parkinson's disease.

Effects of small-world connectivity on noise-induced temporal and spatial order in neural media

International Nuclear Information System (INIS)

Perc, Matjaz

2007-01-01

We present an overview of possible effects of small-world connectivity on noise-induced temporal and spatial order in a two-dimensional network of excitable neural media with FitzHugh-Nagumo local dynamics. Small-world networks are characterized by a given fraction of so-called long-range couplings or shortcut links that connect distant units of the system, while all other units are coupled in a diffusive-like manner. Interestingly, already a small fraction of these long-range couplings can have wide-ranging effects on the temporal as well as spatial noise-induced dynamics of the system. Here we present two main effects. First, we show that the temporal order, characterized by the autocorrelation of a firing-rate function, can be greatly enhanced by the introduction of small-world connectivity, whereby the effect increases with the increasing fraction of introduced shortcut links. Second, we show that the introduction of long-range couplings induces disorder of otherwise ordered, spiral-wave-like, noise-induced patterns that can be observed by exclusive diffusive connectivity of spatial units. Thereby, already a small fraction of shortcut links is sufficient to destroy coherent pattern formation in the media. Although the two results seem contradictive, we provide an explanation considering the inherent scale-free nature of small-world networks, which on one hand, facilitates signal transduction and thus temporal order in the system, whilst on the other hand, disrupts the internal spatial scale of the media thereby hindering the existence of coherent wave-like patterns. Additionally, the importance of spatially versus temporally ordered neural network functioning is discussed

Patterns of caregiver experiences among partners of cancer patients

NARCIS (Netherlands)

Nijboer, C; Triemstra, M; Mulder, M; Sanderman, R; van den Bos, GAM

2000-01-01

This study describes patterns of caregiving experiences in partners of patients with cancer (N=148) over a 6-month period. Caregiving experiences were assessed by means of the Caregiver Reaction Assessment Scale (CRA), which consists of four negative dimensions and one positive subscale: Disrupted

Disruption studies on ASDEX upgrade

International Nuclear Information System (INIS)

Pautasso, G.; Egorov, S.; Finken, K.H.

2003-01-01

Disruptions generate large thermal and mechanical stresses on the tokamak components and are occasionally responsible for damages to the machine. For a future reactor disruptions have a significant impact on the design since all loading conditions must be analyzed in accordance with stricter design criteria (due to safety or difficult maintenance). Therefore the uncertainties affecting the predicted stresses must be reduced as much as possible with a more comprehensive set of measurements and analyses in this generation of experimental machines, and avoidance/predictive methods must be developed further. Disruption studies on ASDEX Upgrade are focused on these subjects, namely on: (1) understanding the physical mechanisms leading to this phenomenon in order to learn to avoid it or to predict its occurrence and to mitigate its effects; (2) analyzing the effects of disruptions on the machine to determine the functional dependence of the thermal and mechanical loads upon the discharge parameters. This allows, firstly, to dimension or reinforce the machine components to withstand these loads and, secondly, to extrapolate them to tokamaks still in the design phase; (3) learning to mitigate the consequence of disruptions, i.e. thermal loads, mechanical forces and runaways with injection of impurity pellets or gas. This paper is focused on most recent results concerning points, i.e. on the analysis of the degree of asymmetry of the forces and on the use of impurity puff for mitigation

Sub-micron magnetic patterns and local variations of adhesion force induced in non-ferromagnetic amorphous steel by femtosecond pulsed laser irradiation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Huiyan; Feng, Yuping [Departament de Física, Universitat Autònoma de Barcelona, Bellaterra, E08193 (Spain); Nieto, Daniel [Microoptics and GRIN Optics Group, Applied Physics Department, University of Santiago de Compostela, E15782 Santiago de Compostela (Spain); García-Lecina, Eva [Unidad de Superficies Metálicas, IK4-CIDETEC, E20009 Donostia-San Sebastián Gipuzkoa (Spain); Mcdaniel, Clare [National Centre for Laser Applications, School of Physics, National University of Ireland, Galway (Ireland); Díaz-Marcos, Jordi [Unitat de Tècniques Nanomètriques, Centres Científics i Tecnològics, Universitat de Barcelona, E08028 Barcelona (Spain); Flores-Arias, María Teresa [Microoptics and GRIN Optics Group, Applied Physics Department, University of Santiago de Compostela, E15782 Santiago de Compostela (Spain); O’Connor, Gerard M. [National Centre for Laser Applications, School of Physics, National University of Ireland, Galway (Ireland); Baró, Maria Dolors [Departament de Física, Universitat Autònoma de Barcelona, Bellaterra, E08193 (Spain); Pellicer, Eva, E-mail: eva.pellicer@uab.cat [Departament de Física, Universitat Autònoma de Barcelona, Bellaterra, E08193 (Spain); and others

2016-05-15

Highlights: • Formation of ripples after femtosecond pulsed laser irradiation (FSPLI) of metallic glass was studied. • Magnetic patterning at the surface of non-ferromagnetic amorphous steel was induced by FSPLI. • The origin of the generated ferromagnetism is the laser-induced devitrification. - Abstract: Periodic ripple and nanoripple patterns are formed at the surface of amorphous steel after femtosecond pulsed laser irradiation (FSPLI). Formation of such ripples is accompanied with the emergence of a surface ferromagnetic behavior which is not initially present in the non-irradiated amorphous steel. The occurrence of ferromagnetic properties is associated with the laser-induced devitrification of the glassy structure to form ferromagnetic (α-Fe and Fe{sub 3}C) and ferrimagnetic [(Fe,Mn){sub 3}O{sub 4} and Fe{sub 2}CrO{sub 4}] phases located in the ripples. The generation of magnetic structures by FSPLI turns out to be one of the fastest ways to induce magnetic patterning without the need of any shadow mask. Furthermore, local variations of the adhesion force, wettability and nanomechanical properties are also observed and compared to those of the as-cast amorphous alloy. These effects are of interest for applications (e.g., biological, magnetic recording, etc.) where both ferromagnetism and tribological/adhesion properties act synergistically to optimize material performance.

Patterns of Sympathetic Responses Induced by Different Stress Tasks

Science.gov (United States)

Fechir, M; Schlereth, T; Purat, T; Kritzmann, S; Geber, C; Eberle, T; Gamer, M; Birklein, F

2008-01-01

Stress tasks are used to induce sympathetic nervous system (SNS) arousal. However, the efficacy and the patterns of SNS activation have not been systematically compared between different tasks. Therefore, we analyzed SNS activation during the following stress tasks: Presentation of negative, positive, and – as a control – neutral affective pictures, Color-Word interference test (CWT), mental arithmetic under time limit, singing a song aloud, and giving a spontaneous talk. We examined 11 healthy subjects and recorded the following SNS parameters: Activation of emotional sweating by quantitative sudometry, skin vasoconstriction by laser-Doppler flowmetry, heart rate by ECG, blood pressure by determination of pulse wave transit time (PWTT), and electromyographic (EMG) activity of the trapezius muscle. Moreover, subjective stress ratings were acquired for each task using a visual analog scale. All tasks were felt significantly stressful when compared to viewing neutral pictures. However, SNS activation was not reliable: Affective pictures did not induce a significant SNS response; singing, giving a talk and mental arithmetic selectively increased heart rate and emotional sweating. Only the CWT globally activated the SNS. Regarding all tasks, induction of emotional sweating, increase of heart rate and blood pressure significantly correlated with subjective stress ratings, in contrast to EMG and skin vasoconstriction. Our results show that the activation of the SNS widely varies depending on the stress task. Different stress tasks differently activate the SNS, which is an important finding when considering sympathetic reactions - in clinical situations and in research. PMID:19018304

Disruptive technologies and transportation : final report.

Science.gov (United States)

2016-06-01

Disruptive technologies refer to innovations that, at first, may be considered unproven, lacking refinement, relatively unknown, or even impractical, but ultimately they supplant existing technologies and/or applications. In general, disruptive techn...

Emerging and Disruptive Technologies.

Science.gov (United States)

Kricka, Larry J

2016-08-01

Several emerging or disruptive technologies can be identified that might, at some point in the future, displace established laboratory medicine technologies and practices. These include increased automation in the form of robots, 3-D printing, technology convergence (e.g., plug-in glucose meters for smart phones), new point-of-care technologies (e.g., contact lenses with sensors, digital and wireless enabled pregnancy tests) and testing locations (e.g., Retail Health Clinics, new at-home testing formats), new types of specimens (e.g., cell free DNA), big biology/data (e.g., million genome projects), and new regulations (e.g., for laboratory developed tests). In addition, there are many emerging technologies (e.g., planar arrays, mass spectrometry) that might find even broader application in the future and therefore also disrupt current practice. One interesting source of disruptive technology may prove to be the Qualcomm Tricorder XPrize, currently in its final stages.

Cell patterning on poly(sodium 4-styrenesulfonate)-patterned fluoropolymer substrate

Energy Technology Data Exchange (ETDEWEB)

Kim, Wan-Joong [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Department of Polymer Science and Engineering, Chungnam National University, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Jung, Chang-Hee; Hwang, In-Tae [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Jung, Chan-Hee, E-mail: jch@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Choi, Jae-Hak, E-mail: jaehakchoi@cnu.ac.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup-si, Jeollabuk-do 580-185 (Korea, Republic of); Department of Polymer Science and Engineering, Chungnam National University, Yuseong-gu, Daejeon 305-764 (Korea, Republic of); Hong, Sung-Kwon [Department of Polymer Science and Engineering, Chungnam National University, Yuseong-gu, Daejeon 305-764 (Korea, Republic of)

2013-10-15

Highlights: •PFA films were functionalized by ion-beam induced surface graft polymerization. •Poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films were prepared. •Well-organized cell patterns were obtained on PSS-patterned PFA films. •This method is useful to fabricate bio-platforms for cell-based biodevices. -- Abstract: The surface functionalization of bio-inert fluoropolymer films through ion beam-induced surface graft polymerization was investigated to control the cellular behavior. The surface of poly(tetrafluoroethylene-co-perfluoropropl vinyl ether) (PFA) films was selectively activated by 150 keV H{sup +} ion implantation in the presence of a pattern mask and sodium 4-styrenesulfonate (SS) was then graft polymerized onto the implanted PFA films to form hydrophilic poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films. The surface of the resulting PSS-patterned PFA films was investigated in terms of the degree of graft polymerization, chemical structure, chemical composition, wettability, and morphology. The analytical results revealed that PSS was selectively grafted onto the implanted regions of the PFA films. Furthermore, in vitro cell culture on the PSS-patterned PFA films exhibited a preferential adhesion and growth of cells onto the PSS-grafted regions, resulting in well-organized 100 μm cell patterns.

Cell patterning on poly(sodium 4-styrenesulfonate)-patterned fluoropolymer substrate

International Nuclear Information System (INIS)

Kim, Wan-Joong; Jung, Chang-Hee; Hwang, In-Tae; Jung, Chan-Hee; Choi, Jae-Hak; Hong, Sung-Kwon

2013-01-01

Highlights: •PFA films were functionalized by ion-beam induced surface graft polymerization. •Poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films were prepared. •Well-organized cell patterns were obtained on PSS-patterned PFA films. •This method is useful to fabricate bio-platforms for cell-based biodevices. -- Abstract: The surface functionalization of bio-inert fluoropolymer films through ion beam-induced surface graft polymerization was investigated to control the cellular behavior. The surface of poly(tetrafluoroethylene-co-perfluoropropl vinyl ether) (PFA) films was selectively activated by 150 keV H + ion implantation in the presence of a pattern mask and sodium 4-styrenesulfonate (SS) was then graft polymerized onto the implanted PFA films to form hydrophilic poly(sodium 4-styrenesulfonate) (PSS)-patterned PFA films. The surface of the resulting PSS-patterned PFA films was investigated in terms of the degree of graft polymerization, chemical structure, chemical composition, wettability, and morphology. The analytical results revealed that PSS was selectively grafted onto the implanted regions of the PFA films. Furthermore, in vitro cell culture on the PSS-patterned PFA films exhibited a preferential adhesion and growth of cells onto the PSS-grafted regions, resulting in well-organized 100 μm cell patterns

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

Energy Technology Data Exchange (ETDEWEB)

Zhou, Changqing; Gao, Liying; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2017-03-01

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.

S-nitrosylation of the IGF-1 receptor disrupts the cell proliferative action of IGF-1.

Science.gov (United States)

Okada, Kazushi; Zhu, Bao-Ting

2017-09-30

The insulin-like growth factor 1 receptor (IGF-1R) is a disulfide-linked heterotetramer containing two α-subunits and two β-subunits. Earlier studies demonstrate that nitric oxide (NO) can adversely affect IGF-1 action in the central nervous system. It is known that NO can induce S-nitrosylation of the cysteine residues in proteins, thereby partly contributing to the regulation of protein function. In the present study, we sought to determine whether S-nitrosylation of the cysteine residues in IGF-1R is an important post-translational modification that regulates its response to IGF-1. Using cultured SH-SY5Y human neuroblastoma cells as an in vitro model, we found that treatment of cells with S-nitroso-cysteine (SNOC), a NO donor that can nitrosylate the cysteine residues in proteins, induces S-nitrosylation of the β subunit of IGF-1R but not its α-subunit. IGF-1Rβ S-nitrosylation by SNOC is coupled with increased dissociation of the IGF-1R protein complex. In addition, disruption of the IGF-1R function resulting from S-nitrosylation of the IGF-1Rβ subunit is associated with disruption of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. Further, we observed that SNOC-induced IGF-1Rβ S-nitrosylation results in a dose-dependent inhibition of cell proliferation and survival. Together, these results suggest that elevated nitrosative stress may result in dysfunction of cellular IGF-1R signaling through S-nitrosylation of the cysteine residues in the IGF-1Rβ subunit, thereby disrupting the downstream PI3K and MAPK signaling functions and ultimately resulting in inhibition of cell proliferation and survival. Copyright © 2017. Published by Elsevier Inc.

FMDV-induced stress granules are disrupted by the viral L-protease

DEFF Research Database (Denmark)

Polacek, Charlotta; Belsham, Graham; McInerney, Gerald

2014-01-01

Eukaryotic cells respond to environmental stress by entering a state of reduced protein synthesis, redirecting resources to damage control and defense. This reduced translation is closely linked to the formation of cytoplasmic stress granules (SGs). SGs are multicomponent foci, which contain...... stalled translation preinitiation complexes, including polyadenylated mRNAs, and several aggregation-prone RNA binding factors, such as the Ras-GAP SH3 domain-binding protein (G3BP) that enable their formation. Once the stress is lifted, the stalled complexes from the SGs are believed to re......-engage in translation, facilitating cellular recovery. A growing body of evidence shows that various viruses can trigger SG formation. However, the presence of SGs may not be beneficial to the virus and many viruses have found ways to circumvent, disrupt or even utilize these granules, suggesting a role for SGs...

Radiation-induced alterations in murine lymphocyte homing patterns. I. Radiolabeling studies

International Nuclear Information System (INIS)

Crouse, D.A.; Feldbush, T.L.; Evans, T.C.

1976-01-01

In vitro x-irradiation of 51 Cr-labeled spleen, lymph node, bone marrow, or thymus cells was found to alter their subsequent in vivo distribution significantly in syngeneic BDF 1 mice. Irradiated cells demonstrated an increased distribution to the liver and a significantly lower retention in the lungs. Cells going to the lymph nodes or Peyer's patches showed a significant exposure-dependent decrease in homing following irradiation. Irradiated lymph node cells homed in greater numbers to the spleen and bone marrow, while irradiated cells from other sources showed no preferential distribution to the same tissues. Sampling host tissues at various times after irradiation and injection did not demonstrate any return to normal patterns of distribution. The alterations in lymphocyte homing observed after in vitro irradiation appear to be due to the elimination of a selective population of lymphocytes or membrane alterations of viable cells, and the detection of these homing changes is in turn dependent upon the relative numbers of various lymphoid subpopulations which are obtained from different cell sources. Radiation-induced alterations in the normal homing patterns of lymphoid cells may thus be of considerable importance in the evaluation of subsequent functional assays in recipient animals

Studies on representative disruption scenarios, associated electromagnetic and heat loads and operation window in ITER

International Nuclear Information System (INIS)

Fujieda, Hirobumi; Shimada, Michiya; Kawano, Yasunori; Ohmori, Junji; Neyatani, Yuzuru; Sugihara, Masayoshi; Gribov, Yuri; Ioki, Kimihiro; Khayrutdinov, Rustan; Lukash, Victor

2007-07-01

The impacts of plasma disruptions on ITER have been investigated in detail to confirm the robustness of the design of the machine to the potential consequential loads. The loads include both electromagnetic (EM) and heat loads on the in-vessel components and the vacuum vessel (VV). Several representative disruption scenarios are specified based on newly derived physics guidelines for the shortest current quench time as well as the maximum product of halo current fraction and toroidal peaking factor arising from disruptions in ITER. Disruption simulations with the DINA code and EM load analyses with a 3D finite element method (FEM) code are performed for these scenarios. Some margins are confirmed in the EM load on in-vessel components due to induced eddy and halo currents for these representative scenarios. However, the margins are not very large. The heat load on various parts of the first wall due to the vertical movement and the thermal quench (TQ) is calculated with a 2D heat conduction code based on the database of heat deposition during disruptions and simulation results with the DINA code. It is found that the beryllium (Be) wall will not melt during the vertical movement. Significant melting is anticipated for the upper Be wall and tungsten divertor baffle due to the TQ after the vertical movement. However, its impact could be substantially mitigated by implementing a reliable detection system of the vertical movement and a mitigation system, e.g., massive noble gas injection (MGI). Some melting of the upper Be wall is anticipated at major disruptions (MD). At least several tens of unmitigated disruptions must be considered even if an advanced prediction/mitigation system is implemented. With these unmitigated disruptions, the loss of Be layer is expected to be within approx. = 30-100 μm/event out of 10 mm thick Be first wall. Various post processing programs of the results simulated with the DINA code, which are developed for the design work, are

Final Report: Safety of Plasma Components and Aerosol Transport During Hard Disruptions and Accidental Energy Release in Fusion Reactor

Energy Technology Data Exchange (ETDEWEB)

Bourham, Mohamed A.; Gilligan, John G.

1999-08-14

Safety considerations in large future fusion reactors like ITER are important before licensing the reactor. Several scenarios are considered hazardous, which include safety of plasma-facing components during hard disruptions, high heat fluxes and thermal stresses during normal operation, accidental energy release, and aerosol formation and transport. Disruption events, in large tokamaks like ITER, are expected to produce local heat fluxes on plasma-facing components, which may exceed 100 GW/m{sup 2} over a period of about 0.1 ms. As a result, the surface temperature dramatically increases, which results in surface melting and vaporization, and produces thermal stresses and surface erosion. Plasma-facing components safety issues extends to cover a wide range of possible scenarios, including disruption severity and the impact of plasma-facing components on disruption parameters, accidental energy release and short/long term LOCA's, and formation of airborne particles by convective current transport during a LOVA (water/air ingress disruption) accident scenario. Study, and evaluation of, disruption-induced aerosol generation and mobilization is essential to characterize database on particulate formation and distribution for large future fusion tokamak reactor like ITER. In order to provide database relevant to ITER, the SIRENS electrothermal plasma facility at NCSU has been modified to closely simulate heat fluxes expected in ITER.

Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

Energy Technology Data Exchange (ETDEWEB)

Wang, Xiang; Zhao, Fang [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Lv, Zhong-ming; Shi, Wei-qin [Jiangsu Provincial Center for Disease Control and Prevention, Nanjing (China); Zhang, Lu-yong, E-mail: lyzhang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing (China); State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Yan, Ming, E-mail: brookming@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)

2016-11-01

Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

International Nuclear Information System (INIS)

Wang, Xiang; Zhao, Fang; Lv, Zhong-ming; Shi, Wei-qin; Zhang, Lu-yong; Yan, Ming

2016-01-01

Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

The Logic of Digital Platform Disruption

DEFF Research Database (Denmark)

Kazan, Erol; Tan, Chee-Wee; Lim, Eric T. K.

Digital platforms are disruptive IT artifacts, because they facilitate the quick release of innovative platform derivatives from third parties (e.g., apps). This study endeavours to unravel the disruptive potential, caused by distinct designs and configurations of digital platforms on market...... environments. We postulate that the disruptive potential of digital platforms is determined by the degree of alignment among the business, technology and platform profiles. Furthermore, we argue that the design and configuration of the aforementioned three elements dictates the extent to which open innovation...... is permitted. To shed light on the disruptive potential of digital platforms, we opted for payment platforms as our unit of analysis. Through interviews with experts and payment providers, we seek to gain an in-depth appreciation of how contemporary digital payment platforms are designed and configured...

Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

Science.gov (United States)

Máthé, Csaba; M-Hamvas, Márta; Vasas, Gábor

2013-01-01

Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs), a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN), an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs) are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS) and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization. PMID:24084787

Microcystin-LR and Cylindrospermopsin Induced Alterations in Chromatin Organization of Plant Cells

Directory of Open Access Journals (Sweden)

Gábor Vasas

2013-09-01

Full Text Available Cyanobacteria produce metabolites with diverse bioactivities, structures and pharmacological properties. The effects of microcystins (MCYs, a family of peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN, an alkaloid type of protein synthesis blocker will be discussed in this review. We are focusing mainly on cyanotoxin-induced changes of chromatin organization and their possible cellular mechanisms. The particularities of plant cells explain the importance of such studies. Preprophase bands (PPBs are premitotic cytoskeletal structures important in the determination of plant cell division plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis. Both cyanotoxins induce the formation of multipolar spindles and disrupted phragmoplasts, leading to abnormal sister chromatid segregation during mitosis. Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY induces programmed cell death: chromatin condensation, nucleus fragmentation, necrosis, alterations of nuclease and protease enzyme activities and patterns. The above effects may be related to elevated reactive oxygen species (ROS and/or disfunctioning of microtubule associated proteins. Specific effects: MCY-LR induces histone H3 hyperphosphorylation leading to incomplete chromatid segregation and the formation of micronuclei. CYN induces the formation of split or double PPB directly related to protein synthesis inhibition. Cyanotoxins are powerful tools in the study of plant cell organization.

Exercise-induced rib stress fractures: potential risk factors related to thoracic muscle co-contraction and movement pattern

DEFF Research Database (Denmark)

Vinther-Knudsen, Archibald; Kanstrup, I-L; Christiansen, E

2006-01-01

The etiology of exercise-induced rib stress fractures (RSFs) in elite rowers is unclear. The purpose of the study was to investigate thoracic muscle activity, movement patterns and muscle strength in elite rowers. Electromyographic (EMG) and 2-D video analysis were performed during ergometer rowing...

Disruption of Core Planar Cell Polarity Signaling Regulates Renal Tubule Morphogenesis but Is Not Cystogenic.

Science.gov (United States)

Kunimoto, Koshi; Bayly, Roy D; Vladar, Eszter K; Vonderfecht, Tyson; Gallagher, Anna-Rachel; Axelrod, Jeffrey D

2017-10-23

Oriented cell division (OCD) and convergent extension (CE) shape developing renal tubules, and their disruption has been associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that localize to primary cilia. Core planar cell polarity (PCP) signaling controls OCD and CE in other contexts, leading to the hypothesis that disruption of PCP signaling interferes with CE and/or OCD to produce PKD. Nonetheless, the contribution of PCP to tubulogenesis and cystogenesis is uncertain, and two major questions remain unanswered. Specifically, the inference that mutation of PKD genes interferes with PCP signaling is untested, and the importance of PCP signaling for cystogenic PKD phenotypes has not been examined. We show that, during proliferative stages, PCP signaling polarizes renal tubules to control OCD. However, we find that, contrary to the prevailing model, PKD mutations do not disrupt PCP signaling but instead act independently and in parallel with PCP signaling to affect OCD. Indeed, PCP signaling that is normally downregulated once development is completed is retained in cystic adult kidneys. Disrupting PCP signaling results in inaccurate control of tubule diameter, a tightly regulated parameter with important physiological ramifications. However, we show that disruption of PCP signaling is not cystogenic. Our results suggest that regulating tubule diameter is a key function of PCP signaling but that loss of this control does not induce cysts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Overvoltage protection for magnetic system during disruption in tokamak

International Nuclear Information System (INIS)

Zhang, Ming; Li, Xiaolong; He, Yang; Zhang, Jun; Chen, Zhongyong; Yu, Kexun

2015-01-01

Highlights: • We investigate the way to limit the plasma disruption overvoltage by using the MOVs. • An overvoltage model of plasma disruption is introduced. • The overvoltage protection scheme has been verified by disruption experiments. • The overvoltage during plasma disruption can be limited to 330 V. - Abstract: During a plasma disruption the magnetic flux in the tokamak changes rapidly, which in most cases will cause high-voltage surges among the magnetic systems and may bring severe damage to the components if there is no overvoltage protection. This paper investigates the way to limit the plasma disruption overvoltage and absorb the energy with the use of metal oxide varistors (MOVs). An overvoltage model of plasma disruption is introduced which can be used for the simulation of plasma disruption and the analysis of the overvoltage. The effectiveness of the overvoltage protection system is validated with disruption experiments. It shows that by optimizing the varistors voltage, the overvoltage during plasma disruption can be limited to an ideal low value. Now the overvoltage protection system has been deployed in J-TEXT tokamak and serves well for daily experiments.

Scalable patterning using laser-induced shock waves

Science.gov (United States)

Ilhom, Saidjafarzoda; Kholikov, Khomidkhodza; Li, Peizhen; Ottman, Claire; Sanford, Dylan; Thomas, Zachary; San, Omer; Karaca, Haluk E.; Er, Ali O.

2018-04-01

An advanced direct imprinting method with low cost, quick, and minimal environmental impact to create a thermally controllable surface pattern using the laser pulses is reported. Patterned microindents were generated on Ni50Ti50 shape memory alloys and aluminum using an Nd: YAG laser operating at 1064 nm combined with a suitable transparent overlay, a sacrificial layer of graphite, and copper grid. Laser pulses at different energy densities, which generate pressure pulses up to a few GPa on the surface, were focused through the confinement medium, ablating the copper grid to create plasma and transferring the grid pattern onto the surface. Scanning electron microscope and optical microscope images show that various patterns were obtained on the surface with high fidelity. One-dimensional profile analysis indicates that the depth of the patterned sample initially increases with the laser energy and later levels off. Our simulations of laser irradiation process also confirm that high temperature and high pressure could be generated when the laser energy density of 2 J/cm2 is used.

Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet.

Science.gov (United States)

Kc, Ranjan; Li, Xin; Forsyth, Christopher B; Voigt, Robin M; Summa, Keith C; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W; Meng, Qing-Jun; Im, Hee-Jeong

2015-11-20

A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications.

Walking through doorways causes forgetting: Event structure or updating disruption?

Science.gov (United States)

Pettijohn, Kyle A; Radvansky, Gabriel A

2016-11-01

According to event cognition theory, people segment experience into separate event models. One consequence of this segmentation is that when people transport objects from one location to another, memory is worse than if people move across a large location. In two experiments participants navigated through a virtual environment, and recognition memory was tested in either the presence or the absence of a location shift for objects that were recently interacted with (i.e., just picked up or set down). Of particular concern here is whether this location updating effect is due to (a) differences in retention intervals as a result of the navigation process, (b) a temporary disruption in cognitive processing that may occur as a result of the updating processes, or (c) a need to manage multiple event models, as has been suggested in prior research. Experiment 1 explored whether retention interval is driving this effect by recording travel times from the acquisition of an object and the probe time. The results revealed that travel times were similar, thereby rejecting a retention interval explanation. Experiment 2 explored whether a temporary disruption in processing is producing the effect by introducing a 3-second delay prior to the presentation of a memory probe. The pattern of results was not affected by adding a delay, thereby rejecting a temporary disruption account. These results are interpreted in the context of the event horizon model, which suggests that when there are multiple event models that contain common elements there is interference at retrieval, which compromises performance.

Low-m magnetic modes activity and disruptions in Tokamaks discharges

International Nuclear Information System (INIS)

Cotsaftis, Michel.