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Sample records for drain induced barrier

  1. PNPN tunnel FET with controllable drain side tunnel barrier width: Proposal and analysis

    NASA Astrophysics Data System (ADS)

    Abdi, Dawit Burusie; Jagadesh Kumar, M.

    2015-10-01

    A detailed study of a technique to realize a PNPN tunnel field effect transistor (TFET) with a controllable tunnel barrier width on the drain side is reported in this paper. By using the charge plasma concept on a doped N+/P- starting structure, we have demonstrated the possibility of realizing the PNPN TFET without the need for any additional chemically doped junctions. We have showed that using electrostatic doping on the drain side of TFETs provides a new design parameter, the gate-drain electrode gap. This gate-drain electrode gap can be used to control the ambipolar current in TFETs by controlling the tunneling barrier width at the channel-drain junction.

  2. A Channel Stop Defined, Barrier And Drain Antiblooming Structure For Virtual Phase Ccd Image Sensors

    NASA Astrophysics Data System (ADS)

    Keenan, W. F.; Hosack, H. H.

    1987-04-01

    A new barrier and drain antiblooming architecture has been developed for virtual phase CCD image sensors. In this structure the drain is isolated from the pixel wells by the channel stop implant except in the antiblooming control region, where it is the same as the normal pixel barrier which exists along the direction of charge transfer. In addition, in this structure the drain is placed beneath the virtual electrode to eliminate low voltage breakdown effects. The unique organization of this structure allows the same potential levels to be used in both the antiblooming barrier and the transfer barrier. This multiple use of the same potential region greatly simplifies the processing needed for this type of device. The structure is formed by the process steps normally used to fabricate the sensor without antiblooming, except for one additional ion implant and pattern level to form the antiblooming drain. The antibooming action is continuous during integration and readout, and has extremely high overload tolerance. These features make this structure the preferred form of antiblooming for applications which have very high overload, such as flash lamp illumination. The process economy inherent in this anti-blooming structure results in higher sensor yields and lower manufacturing costs.

  3. Ferroelectric Schottky barrier tunnel FET with gate-drain underlap: Proposal and investigation

    NASA Astrophysics Data System (ADS)

    Kale, Sumit; Kondekar, P. N.

    2016-01-01

    In this paper, for the first time, a novel ferroelectric schottky barrier tunnel FET (Fe SB-TFET) is proposed and investigated. The Fe SB-TFET consists of ferroelectric gate stack with highly doped pocket at the source/drain and channel interface. In addition, for the suppression of ambipolar leakage current (IAMB), gate-drain underlap is employed. By using ferroelectric gate stack, we effectively amplified the applied gate voltage to enhance electric field for the reduction of tunneling barrier width at the source side schottky barrier. As a result, the increased tunneling probability improves the device performance in terms of high ION, high ION/IOFF ratio, reduced IAMB and low subthreshold swing (SS) as compared to the conventional SB-TFET having double pocket. We also investigate the influence of highly doped pocket (HDP) doping concentration and length on the device performance.

  4. Charge trapping induced drain-induced-barrier-lowering in HfO2/TiN p-channel metal-oxide-semiconductor-field-effect-transistors under hot carrier stress

    NASA Astrophysics Data System (ADS)

    Lo, Wen-Hung; Chang, Ting-Chang; Tsai, Jyun-Yu; Dai, Chih-Hao; Chen, Ching-En; Ho, Szu-Han; Chen, Hua-Mao; Cheng, Osbert; Huang, Cheng-Tung

    2012-04-01

    This letter studies the channel hot carrier stress (CHCS) behaviors on high dielectric constant insulator and metal gate HfO2/TiN p-channel metal-oxide-semiconductor field effect transistors. It can be found that the degradation is associated with electron trapping, resulting in Gm decrease and positive Vth shift. However, Vth under saturation region shows an insignificant degradation during stress. To compare that, the CHC-induced electron trapping induced DIBL is proposed to demonstrate the different behavior of Vth between linear and saturation region. The devices with different channel length are used to evidence the trapping-induced DIBL behavior.

  5. Liquid draining shut-off induced geyser and slosh wave excitation at suction dip during draining in microgravity

    NASA Technical Reports Server (NTRS)

    Hung, R. J.; Shyu, K. L.

    1992-01-01

    The dynamical behavior of vapor ingestion, liquid residual at the incipience of suction dip, liquid hydrogen shut-off at the incipience of suction dip, and slosh wave excitation under normal and various reduced gravity environments and different flow rates of liquid during draining have been investigated. It shows that the liquid residual at the incipience of suction dip increases as the values of gravity environment decrease from normal gravity to lower reduced gravity, and also that the liquid residual increases as the flow rates of liquid increase during the courses of liquid hydrogen draining. It also shows that slosh waves accompanied by strong geyser are developed for surge-related flowfields at the moment of liquid hydrogen shut-off. Slosh wave excitation, during the liquid hydrogen shut-off, shift the fluid mass distribution in the container which imposes time-dependent variation in spacecraft moment of inertia.

  6. VEGF-A produced by chronically inflamed tissue induces lymphangiogenesis in draining lymph nodes

    PubMed Central

    Halin, Cornelia; Tobler, Nadja E.; Vigl, Benjamin; Brown, Lawrence F.

    2007-01-01

    Lymphangiogenesis is involved in tumor cell metastasis and plays a major role in chronic inflammatory disorders. To investigate the role of lymphangiogenesis in inflammation, we induced and maintained delayed-type hypersensitivity (DTH) reactions in the ears of mice and then analyzed the resulting lymphangiogenesis in the inflamed tissue and draining lymph nodes (LNs) by quantitative fluorescence-activated cell sorting (FACS) and by immunofluorescence. Long-lasting inflammation induced a significant increase in the number of lymphatic endothelial cells, not only in the inflamed ears but also in the ear-draining auricular LNs. Inflammation-induced lymphangiogenesis was potently blocked by systemic administration of a vascular endothelial growth factor (VEGF)-A neutralizing antibody. Surprisingly, tissue inflammation specifically induced LN lymphangiogenesis but not LN angiogenesis. These findings were explained by analysis of both VEGF-A protein and mRNA levels, which revealed that VEGF-A was expressed at high mRNA and protein levels in inflamed ears but that expression was increased only at the protein level in activated LNs. Inflammation-induced lymphangiogenesis in LNs was independent of the presence of nodal B lymphocytes, as shown in B cell-deficient mice. Our data reveal that chronic inflammation actively induces lymphangiogenesis in LNs, which is controlled remotely, by lymphangiogenic factors produced at the site of inflammation. PMID:17625067

  7. Barrier reduction via implementation of InGaN interlayer in wafer-bonded current aperture vertical electron transistors consisting of InGaAs channel and N-polar GaN drain

    SciTech Connect

    Kim, Jeonghee Laurent, Matthew A.; Li, Haoran; Lal, Shalini; Mishra, Umesh K.

    2015-01-12

    This letter reports the influence of the added InGaN interlayer on reducing the inherent interfacial barrier and hence improving the electrical characteristics of wafer-bonded current aperture vertical electron transistors consisting of an InGaAs channel and N-polar GaN drain. The current-voltage characteristics of the transistors show that the implementation of N-polar InGaN interlayer effectively reduces the barrier to electron transport across the wafer-bonded interface most likely due to its polarization induced downward band bending, which increases the electron tunneling probability. Fully functional wafer-bonded transistors with nearly 600 mA/mm of drain current at V{sub GS} = 0 V and L{sub go} = 2 μm have been achieved, and thus demonstrate the feasibility of using wafer-bonded heterostructures for applications that require active carrier transport through both materials.

  8. Barrier island bistability induced by biophysical interactions

    NASA Astrophysics Data System (ADS)

    Durán Vinent, Orencio; Moore, Laura J.

    2015-02-01

    Barrier islands represent about 10% of the world’s coastline, sustain rich ecosystems, host valuable infrastructure and protect mainland coasts from storms. Future climate-change-induced increases in the intensity and frequency of major hurricanes and accelerations in sea-level rise will have a significant impact on barrier islands--leading to increased coastal hazards and flooding--yet our understanding of island response to external drivers remains limited. Here, we find that island response is intrinsically bistable and controlled by previously unrecognized dynamics: the competing, and quantifiable, effects of storm erosion, sea-level rise, and the aeolian and biological processes that enable and drive dune recovery. When the biophysical processes driving dune recovery dominate, islands tend to be high in elevation and vulnerability to storms is minimized. Alternatively, when the effects of storm erosion dominate, islands may become trapped in a perpetual state of low elevation and maximum vulnerability to storms, even under mild storm conditions. When sea-level rise dominates, islands become unstable and face possible disintegration. This quantification of barrier island dynamics is supported by data from the Virginia Barrier Islands, USA and provides a broader context for considering island response to climate change and the likelihood of potentially abrupt transitions in island state.

  9. Radiation-enhanced gate-induced-drain-leakage current in the 130 nm partially-depleted SOI pMOSFET

    NASA Astrophysics Data System (ADS)

    Peng, Chao; Hu, Zhiyuan; Ning, Bingxu; Dai, Lihua; Bi, Dawei; Zhang, Zhengxuan

    2015-04-01

    The total ionizing dose (TID) effect of the pMOSFET from 130 nm partially-depleted silicon-on-insulator (PDSOI) is investigated. The data obtained from 60Co γ-ray irradiation experiments indicate that input/output (I/O) device is more susceptible to TID effect than the core device. An anomalous off-state leakage increase is observed for I/O pMOSFET when drain is biased at a high voltage after irradiation. It is proved that this radiation-induced leakage relates to the enhanced gate-induce-drain-leakage (GIDL). Both the radiation-induced interface traps at the gate-oxide/body interface and the oxide trapped charges in the buried oxide (BOX) are responsible for the growth of the leakage current. These conclusions are also verified by the TCAD simulations. The isothermal annealing can recover the leakage current to the pre-irradiation level.

  10. An analysis of molten-corium-induced failure of drain pipes in BWR Mark 2 containments

    SciTech Connect

    Taleyarkhan, R.P. ); Podowski, M.Z. )

    1991-01-01

    This study has focused on mechanistic simulation and analysis of potential failure modes for inpedestal drywell drain pipes in the Limerick boiling water reactor (BWR) Mark 2 containment. Physical phenomena related to surface tension breakdown, heatup, melting, ablation, crust formation and failure, and core material relocation into drain pipes with simultaneous melting of pipe walls were modeled and analyzed. The results of analysis have been used to assess the possibility of drain pipe failure and the resultant loss of pressure-suppression capability. Estimates have been made for the timing and amount of molten corium released to the wetwell. The study has revealed that significantly different melt progression sequences can result depending upon the failure characteristics of the frozen metallic crust which forms over the drain cover during the initial stages of debris pour. Another important result is that it can take several days for the molten fuel to ablate the frozen metallic debris layer -- if the frozen layer has cooled below 1100 K before fuel attack. 10 refs., 3 figs., 4 tabs.

  11. Hemovac drain

    MedlinePlus

    ... gloves Five or 6 cotton swabs Gauze pads Clean soapy water Plastic trash bag Surgical tape Waterproof pad or ... Use a cotton swab dipped in the soapy water to clean the skin around the drain. Do this 3 ...

  12. Impact of extension implantation conditions of fin field-effect transistors on gate-induced drain leakage

    NASA Astrophysics Data System (ADS)

    Matsukawa, Takashi; Liu, Yongxun; Mori, Takahiro; Morita, Yukinori; O'uchi, Shinichi; Otsuka, Shintaro; Migita, Shinji; Masahara, Meishoku

    2016-04-01

    The influence of the extension doping conditions on gate-induced drain leakage (GIDL) has been investigated to optimize fin field-effect transistors (FinFETs) for ultralow-power (ULP) applications. An increased GIDL for a smaller fin thickness and a dependence on the implanted ion species, i.e., a larger GIDL for As than for P, are recognized. These results suggest that the residual defects due to extension doping increase the GIDL, and the suppression of the defects by the optimization of the doping process is the key to the optimization of FinFETs for ULP applications.

  13. The n-type metal-oxide semiconductor field-effect transistor bias impact on the modelling of the gate-induced drain leakage current

    NASA Astrophysics Data System (ADS)

    Touhami, A.; Bouhdada, A.

    2002-12-01

    The band-to-band tunnelling (BBT) effect in an n-type metal-oxide semiconductor field-effect transistor (n-MOSFET) is attributed not only to the transverse electric field ET but also to the lateral electric field EL in the gate-to-drain overlap region. The main sources of these electric fields are the gate-source (Vgs) and drain-source (Vds) voltages. The modelling of the gate-induced drain leakage current, Igidl, associated with BBT remains always dependent on the drain-gate voltage, Vdg, whatever the applied values of Vgs and Vds, which cannot describe accurately the evolution of the Igidl current according to biases. Therefore, it is necessary to clarify the impact of Vgs and Vds separately. In this paper, we propose a new model of the Igidl current, which can describe the BBT effect in n-MOSFETs under various Vgs and Vds biases.

  14. Detergent-induced epidermal barrier dysfunction and its prevention.

    PubMed

    Okuda, Minehiro; Yoshiike, Takashi; Ogawa, Hideoki

    2002-12-01

    Various detergents are used as skin cleansing products. In some cases, skin cleanser removes not only dirt but also valuable skin lipids. Therefore, detergents may disrupt epidermal barrier function despite that using of detergents are required for good skin hygiene. Lipid supplements can reverse detergent-induced dysfunction of the skin barrier. Elevated transepidermal water loss (TEWL) and riboflavin penetration in 5% SLS-treated rat and human skin were reversed by supplementation of monoglyceride (MG), squalene (SQ), cholesterol ester (CE) and pseudo-ceramide (Cer2). MG and Cer2 achieved the best results. MG appears to inhibit elution of intercellular ceramides, since more ceramides remained when the detergent was supplemented with MG. Topical application of Cer2 is not effective for recovery from artificially induced barrier disruption, but supplemented Cer2 into skin cleanser has a beneficial effect for prevention of detergent-induced barrier disruption. In conclusion, the prevention of barrier disruption is most important matter for maintaining skin health and barrier function. Therefore, we think that Cer2-supplemented skin cleanser is useful for conservation of skin barrier function. PMID:12443839

  15. Influence of source and drain contacts on the properties of indium-gallium-zinc-oxide thin-film transistors based on amorphous carbon nanofilm as barrier layer.

    PubMed

    Luo, Dongxiang; Xu, Hua; Zhao, Mingjie; Li, Min; Xu, Miao; Zou, Jianhua; Tao, Hong; Wang, Lei; Peng, Junbiao

    2015-02-18

    Amorphous indium-gallium-zinc-oxide thin film transistors (α-IGZO TFTs) with damage-free back channel wet-etch (BCE) process were achieved by introducing a carbon nanofilm as a barrier layer. We investigate the effects of different source-and-drain (S/D) materials on TFT performance. We find the TFT with Ti/C S/D electrodes exhibits a superior performance with higher output current, lower threshold voltage, and higher effective electron mobility compared to that of Mo/C S/D electrodes. Transmittance electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) are employed to analysis the interfacial interaction between S/D metal/C/α-IGZO layers. The results indicate that the better performance of TFTs with Ti/C electrodes should be attributed to the formations of Ti-C and Ti-O at the Ti/C-contact regions, which lead to a lower contact resistance, whereas Mo film is relatively stable and does not react easily with C nanofilm, resulting in a nonohmic contact behavior between Mo/C and α-IGZO layer. However, both kinds of α-IGZO TFTs show good stability under thermal bias stress, indicating that the inserted C nanofilms could avoid the impact on the α-IGZO channel regions during S/D electrodes formation. Finally, we successfully fabricated a high-definition active-matrix organic lighting emitting diode prototype driven by α-IGZO TFTs with Ti/C electrodes in a pilot line. PMID:25619280

  16. Extraction of Distance Between Interface Trap and Oxide Trap from Random Telegraph Noise in Gate-Induced Drain Leakage.

    PubMed

    Seo, Youngsoo; Yoo, Sungwon; Shin, Joonha; Kim, Hyunsoo; Kim, Hyunsuk; Jeon, Sangbin; Shin, Hyungcheol

    2016-05-01

    This paper presents an analysis of the Random Telegraph Noise (RTN) of the Gate-Induced Drain Leakage (GIDL) of a Metal Oxide Semiconductor Field Effect Transistor (MOSFET). The RTN data that was measured and analytical equations are used to extract the values of the parameters for the vertical distance of the oxide trap from the interface and of the energy level of the interface trap. These values and equations allow for the distance r between the interface trap and the oxide trap to be extracted. For the first time, the accurate field enhancement factor γ(F), which depends on the magnitude of the electric field at the Si/SiO2 interface, was used to calculate the current ratio before and after the electron trapping, and the value extracted for r is completely different depending on the enhancement factor that is used. PMID:27483908

  17. Effect of asymmetrical double-pockets and gate-drain underlap on Schottky barrier tunneling FET: Ambipolar conduction vs. high frequency performance

    NASA Astrophysics Data System (ADS)

    Shaker, Ahmed; Ossaimee, Mahmoud; Zekry, A.

    2016-08-01

    In this paper, a proposed structure based on asymmetrical double pockets SB-TFET with gate-drain underlap is presented. 2D extensive modeling and simulation, using Silvaco TCAD, were carried out to study the effect of both underlap length and pockets' doping on the transistor performance. It was found that the underlap from the drain side suppresses the ambipolar conduction and doesn't enhance the high-frequency characteristics. The enhancement of the high-frequency characteristics could be realized by increasing the doping of the drain pocket over the doping of the source pocket. An optimum choice was found which gives the conditions of minimum ambipolar conduction, maximum ON current and maximum cut-off frequency. These enhancements render the device more competitive as a nanometer transistor.

  18. Damage of vascular endothelial barrier induced by explosive blast and its clinical significance.

    PubMed

    Wang, Jian-Min; Chen, Jing

    2016-06-01

    In recent years, injuries induced by explosive blast have got more and more attention owing to weapon development and frequent terrorist activities. Tear, bleeding and edema of tissues and organs are the main manifestations of blast shock wave damage. Vascular endothelial barrier is the main defense of tissues and organs' integrity. This article aims to discuss possible mechanisms of endothelial barrier damage induced by explosive blast and main manifestations of blood brain barrier, bloodeair barrier, and intestinal vascular barrier impairments. In addition, the main regulatory factors of vascular permeability are also summarized so as to provide theoretical basis for prevention and cure of vascular endothelial barrier damage resulting from explosive blast. PMID:27321288

  19. Effects of trap-assisted tunneling on gate-induced drain leakage in silicon-germanium channel p-type FET for scaled supply voltages

    NASA Astrophysics Data System (ADS)

    Tiwari, Vishal A.; Divakaruni, Rama; Hook, Terence B.; Nair, Deleep R.

    2016-04-01

    Silicon-germanium is considered as an alternative channel material to silicon p-type FET (pFET) for the development of energy efficient high performance transistors for 28 nm and beyond in a high-k metal gate technology because of its lower threshold voltage and higher mobility. However, gate-induced drain leakage (GIDL) is a concern for high threshold voltage device design because of tunneling at reduced bandgap. In this work, the trap-assisted tunneling and band-to-band tunneling (BTBT) effects on GIDL is analyzed and modeled for SiGe pFETs. Experimental results and Monte Carlo simulation results reveal that the pre-halo germanium pre-amorphization implant used to contain the short channel effects contribute to GIDL at the drain sidewall in addition to GIDL due to BTBT in SiGe devices. The results are validated by comparing the experimental observations with the numerical simulation and a set of calibrated models are used to describe the GIDL mechanisms for various drain and gate bias.

  20. SIV antigen immunization induces transient antigen-specific T cell responses and selectively activates viral replication in draining lymph nodes in retroviral suppressed rhesus macaques

    PubMed Central

    2011-01-01

    Background HIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4+ T cell responses to many pathogens, but HIV-specific responses remain deficient. Similarly, therapeutic immunization with HIV antigens of chronically infected, ART treated subjects results in poor induction of HIV-specific CD4 responses. In this study, we used a macaque model of ART treatment during chronic infection to study the virologic consequences of SIV antigen stimulation in lymph nodes early after immunization. Rhesus CMV (RhCMV) seropositive, Mamu A*01 positive rhesus macaques were chronically infected with SIVmac251 and treated with ART. The immune and viral responses to SIV gag and RhCMV pp65 antigen immunization in draining lymph nodes and peripheral blood were analyzed. Animals were immunized on contralateral sides with SIV gag and RhCMV pp65 encoding plasmids, which allowed lymph nodes draining each antigen to be obtained at the same time from the same animal for direct comparison. Results We observed that both SIV and RhCMV immunizations stimulated transient antigen-specific T cell responses in draining lymph nodes. The RhCMV-specific responses were potent and sustained (50 days post-immunization) in the periphery, while the SIV-specific responses were transient and extinguished quickly. The SIV antigen stimulation selectively induced transient SIV replication in draining lymph nodes. Conclusions The data are consistent with a model whereby viral replication in response to SIV antigen stimulation limits the generation of SIV antigen-specific responses and suggests a potential mechanism for the early loss and poor HIV-specific CD4+ T cell response observed in HIV-infected individuals. PMID:21752277

  1. Zinc modulates cytokine-induced lung epithelial cell barrier permeability.

    PubMed

    Bao, Shenying; Knoell, Daren L

    2006-12-01

    Apoptosis plays a causative role in acute lung injury in part due to epithelial cell loss. We recently reported that zinc protects the lung epithelium during inflammatory stress whereas depletion of intracellular zinc enhances extrinsic apoptosis. In this investigation, we evaluated the relationship between zinc, caspase-3, and cell-to-cell contact via proteins that form the adherens junction complex. Cell adhesion proteins are directly responsible for formation of the mechanical barrier of the lung epithelium. We hypothesized that exposure to inflammatory cytokines, in conjunction with zinc deprivation, would induce caspase-3, leading to degradation of junction proteins, loss of cell-to-cell contact, and compromised barrier function. Primary human upper airway and type I/II alveolar epithelial cultures were obtained from multiple donors and exposed to inflammatory stimuli that provoke extrinsic apoptosis in addition to depletion of intracellular zinc. We observed that zinc deprivation combined with tumor necrosis factor-alpha, interferon-gamma, and Fas receptor ligation accelerates caspase-3 activation, proteolysis of E-cadherin and beta-catenin, and cellular apoptosis, leading to increased paracellular leak across monolayers of both upper airway and alveolar lung epithelial cultures. Zinc supplementation inhibited apoptosis and paracellular leak, whereas caspase inhibition was less effective. We conclude that zinc is a vital factor in the lung epithelium that protects against death receptor-mediated apoptosis and barrier dysfunction. Furthermore, our findings suggest that although caspase-3 inhibition reduces lung epithelial apoptosis it does not prevent mechanical dysfunction. These findings facilitate future studies aimed at developing therapeutic strategies to prevent acute lung injury. PMID:16844947

  2. Drain cleaner poisoning

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002779.htm Drain cleaner poisoning To use the sharing features on this page, please enable JavaScript. Drain cleaners contain very dangerous chemicals that can be ...

  3. Analysis of gate-induced drain leakage characteristics and threshold voltage modulation of plasma-doped FinFETs for low-power applications

    NASA Astrophysics Data System (ADS)

    Lee, Ji-myoung; Cho, Keun Hwi; Kim, Dong-won; Chung, Ilsub

    2016-04-01

    FinFET devices were fabricated using plasma doping both at the source and drain extensions and in the channel region. In an effort to overcome dopant loss after the strip process, oxide buffer layers were deposited prior to plasma doping. Owing to the oxide buffer, 76% of the dopants were retained after the strip process and even after ashing, thereby keeping a high doping concentration of over 1 × 1020 atoms/cm3 on the surface of the Si fin. The gate-induced drain leakage (GIDL) current was decreased by 2 orders of magnitude due to the shallow and abrupt plasma doping, compared to the performance with an ion implantation method. The threshold voltage (V th) was shifted by 250 mV through plasma doping of the channel. The doping conformality was evaluated using electrical measurements and a newly-proposed method based on the GIDL data with various fin widths. The conformal doping profile with a smaller dopant loss provides a smaller GIDL current.

  4. Ionic liquid gating on atomic layer deposition passivated GaN: Ultra-high electron density induced high drain current and low contact resistance

    NASA Astrophysics Data System (ADS)

    Zhou, Hong; Du, Yuchen; Ye, Peide D.

    2016-05-01

    Herein, we report on achieving ultra-high electron density (exceeding 1014 cm-2) in a GaN bulk material device by ionic liquid gating, through the application of atomic layer deposition (ALD) of Al2O3 to passivate the GaN surface. Output characteristics demonstrate a maximum drain current of 1.47 A/mm, the highest reported among all bulk GaN field-effect transistors, with an on/off ratio of 105 at room temperature. An ultra-high electron density exceeding 1014 cm-2 accumulated at the surface is confirmed via Hall-effect measurement and transfer length measurement. In addition to the ultra-high electron density, we also observe a reduction of the contact resistance due to the narrowing of the Schottky barrier width on the contacts. Taking advantage of the ALD surface passivation and ionic liquid gating technique, this work provides a route to study the field-effect and carrier transport properties of conventional semiconductors in unprecedented ultra-high charge density regions.

  5. The Draining Cylinder

    ERIC Educational Resources Information Center

    James Graham-Eagle

    2009-01-01

    This article explores the time it takes for a liquid to drain from a cylindrical container through a hole in the bottom. Using dimensional analysis and some thought experiments this time is determined and Torricelli's law derived as a consequence. Finally, the effect of pouring liquid into the container as it drains is considered.

  6. Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.

    PubMed

    Schweitzer, Kelly S; Hatoum, Hadi; Brown, Mary Beth; Gupta, Mehak; Justice, Matthew J; Beteck, Besem; Van Demark, Mary; Gu, Yuan; Presson, Robert G; Hubbard, Walter C; Petrache, Irina

    2011-12-01

    The epithelial and endothelial cells lining the alveolus form a barrier essential for the preservation of the lung respiratory function, which is, however, vulnerable to excessive oxidative, inflammatory, and apoptotic insults. Whereas profound breaches in this barrier function cause pulmonary edema, more subtle changes may contribute to inflammation. The mechanisms by which cigarette smoke (CS) exposure induce lung inflammation are not fully understood, but an early alteration in the epithelial barrier function has been documented. We sought to investigate the occurrence and mechanisms by which soluble components of mainstream CS disrupt the lung endothelial cell barrier function. Using cultured primary rat microvascular cell monolayers, we report that CS induces endothelial cell barrier disruption in a dose- and time-dependent manner of similar magnitude to that of the epithelial cell barrier. CS exposure triggered a mechanism of neutral sphingomyelinase-mediated ceramide upregulation and p38 MAPK and JNK activation that were oxidative stress dependent and that, along with Rho kinase activation, mediated the endothelial barrier dysfunction. The morphological changes in endothelial cell monolayers induced by CS included actin cytoskeletal rearrangement, junctional protein zonula occludens-1 loss, and intercellular gap formation, which were abolished by the glutathione modulator N-acetylcysteine and ameliorated by neutral sphingomyelinase inhibition. The direct application of ceramide recapitulated the effects of CS, by disrupting both endothelial and epithelial cells barrier, by a mechanism that was redox and apoptosis independent and required Rho kinase activation. Furthermore, ceramide induced dose-dependent alterations of alveolar microcirculatory barrier in vivo, measured by two-photon excitation microscopy in the intact rat. In conclusion, soluble components of CS have direct endothelial barrier-disruptive effects that could be ameliorated by glutathione

  7. Ascorbate Reverses High Glucose- and RAGE-induced Leak of the Endothelial Permeability Barrier

    PubMed Central

    Meredith, M. Elizabeth; Qu, Zhi-chao; May, James M.

    2014-01-01

    High glucose concentrations due to diabetes increase leakage of plasma constituents across the endothelial permeability barrier. We sought to determine whether vitamin C, or ascorbic acid (ascorbate), could reverse such high glucose-induced increases in endothelial barrier permeability. Human umbilical vein endothelial cells and two brain endothelial cell lines cultured at 25 mM glucose showed increases in endothelial barrier permeability to radiolabeled inulin compared to cells cultured at 5 mM glucose. Acute loading of the cells for 30–60 min with ascorbate before the permeability assay prevented the high glucose-induced increase in permeability and decreased basal permeability at 5 mM glucose. High glucose-induced barrier leakage was mediated largely by activation of the receptor for advanced glycation end products (RAGE), since it was prevented by RAGE blockade and mimicked by RAGE ligands. Intracellular ascorbate completely prevented RAGE ligand-induced increases in barrier permeability. The high glucose-induced increase in endothelial barrier permeability was also acutely decreased by several cell-penetrant antioxidants, suggesting that at least part of the ascorbate effect could be due to its ability to act as an antioxidant. PMID:24472555

  8. Short-Channel Tunneling Field-Effect Transistor with Drain-Overlap and Dual-Metal Gate Structure for Low-Power and High-Speed Operations.

    PubMed

    Yoon, Young Jun; Eun, Hye Rim; Seo, Jae Hwa; Kang, Hee-Sung; Lee, Seong Min; Lee, Jeongmin; Cho, Seongjae; Tae, Heung-Sik; Lee, Jung-Hee; Kang, In Man

    2015-10-01

    We have investigated and proposed a highly scaled tunneling field-effect transistor (TFET) based on Ge/GaAs heterojunction with a drain overlap to suppress drain-induced barrier thinning (DIBT) and improve low-power (LP) performance. The highly scaled TFET with a drain overlap achieves lower leakage tunneling current because of the decrease in tunneling events between the source and drain, whereas a typical short-channel TFET suffers from a great deal of tunneling leakage current due to the DIBT at the off-state. However, the drain overlap inevitably increases the gate-to-drain capacitance (Cgd) because of the increase in the overlap capacitance (Cov) and inversion capacitance (Cinv). Thus, in this work, a dual-metal gate structure is additionally applied along with the drain overlap. The current performance and the total gate capacitance (Cgg) of the device with a dual-metal gate can be possibly controlled by adjusting the metal gate workfunction (φgate) and φoverlap-gate in the overlapping regions. As a result, the intrinsic delay time (τ) is greatly reduced by obtaining lower Cgg divided by the on-state current (Ion), i.e., Cgg/Ion. We have successfully demonstrated excellent LP and high-speed performance of a highly scaled TFET by adopting both drain overlap and dual-metal gate with DIBT minimization. PMID:26726346

  9. Functional CD25- and CD25+ mucosal regulatory T cells are induced in gut-draining lymphoid tissue within 48 h after oral antigen application.

    PubMed

    Hauet-Broere, Femke; Unger, Wendy W J; Garssen, Johan; Hoijer, Maarten A; Kraal, Georg; Samsom, Janneke N

    2003-10-01

    Oral antigen application induces tolerance, leading to suppression of a subsequent systemic challenge with this antigen. The suppression is mediated by mucosal regulatory T (Tr) cells that may differentiate from naive peripheral T cells in the gut-draining lymphoid tissue. However, little is known about the initial steps of this differentiation process. In this study we show that 48 h after oral OVA treatment, antigen-specific T cells in mesenteric lymph nodes (MLN) and Peyer's Patches (PP) were activated and had divided up to four times. The first division was already seen in PP after 24 h. Analysis of surface marker expression and cytokine secretion of the dividing antigen-specific T cells revealed that they sequentially obtained an activation- and memory-like phenotype. These cells secreted IL-2 in most stages of division but only transiently IFN-gamma whereas no IL-4 or IL-10 secretion was detected. Remarkably, 48 h after antigen application, isolated dividing cells were suppressive, as they transferred tolerance to naive mice. Even though CD25 was expressed heterogeneously, both CD25(+) and CD25(-) OVA-specific T cells from MLN could transfer tolerance. Together these findings show that differentiation of functional Tr cells occurs in the MLN and PP within 2 days after antigen ingestion and involves the generation of CD25(+) and CD25(-) antigen-specific T cells. PMID:14515264

  10. Stacking fault induced tunnel barrier in platelet graphite nanofiber

    SciTech Connect

    Lan, Yann-Wen E-mail: ywlan@phys.sinica.edu.tw; Chang, Yuan-Chih; Chang, Chia-Seng; Chen, Chii-Dong E-mail: ywlan@phys.sinica.edu.tw; Chang, Wen-Hao; Li, Yuan-Yao

    2014-09-08

    A correlation study using image inspection and electrical characterization of platelet graphite nanofiber devices is conducted. Close transmission electron microscopy and diffraction pattern inspection reveal layers with inflection angles appearing in otherwise perfectly stacked graphene platelets, separating nanofibers into two domains. Electrical measurement gives a stability diagram consisting of alternating small-large Coulomb blockade diamonds, suggesting that there are two charging islands coupled together through a tunnel junction. Based on these two findings, we propose that a stacking fault can behave as a tunnel barrier for conducting electrons and is responsible for the observed double-island single electron transistor characteristics.

  11. Stacking fault induced tunnel barrier in platelet graphite nanofiber

    NASA Astrophysics Data System (ADS)

    Lan, Yann-Wen; Chang, Wen-Hao; Li, Yuan-Yao; Chang, Yuan-Chih; Chang, Chia-Seng; Chen, Chii-Dong

    2014-09-01

    A correlation study using image inspection and electrical characterization of platelet graphite nanofiber devices is conducted. Close transmission electron microscopy and diffraction pattern inspection reveal layers with inflection angles appearing in otherwise perfectly stacked graphene platelets, separating nanofibers into two domains. Electrical measurement gives a stability diagram consisting of alternating small-large Coulomb blockade diamonds, suggesting that there are two charging islands coupled together through a tunnel junction. Based on these two findings, we propose that a stacking fault can behave as a tunnel barrier for conducting electrons and is responsible for the observed double-island single electron transistor characteristics.

  12. Modeling Oxidation Induced Stresses in Thermal Barrier Coatings

    NASA Technical Reports Server (NTRS)

    Ferguson, B. L.; Freborg, A. M.; Petrus, G. J.; Brindley, William J.

    1998-01-01

    The use of thermal barrier coatings (TBC's) in gas turbines has increased dramatically in recent years, due mainly to the need for component protection from ever increasing service temperatures. Oxidation of the bond coat has been identified as an important contributing factor to spallation of the ceramic top coat during service. Additional variables found to influence TBC thermal cycle life include bond coat coefficient of thermal expansion, creep behavior of both the ceramic and bond coat layers, and modulus of elasticity. The purpose of this work was to characterize the effects of oxidation on the stress states within the TBC system, as well as to examine the interaction of oxidation with other factors affecting TBC life.

  13. Scalability of Gate/N- Overlapped Lightly Doped Drain in Deep-Submicrometer Regime

    NASA Astrophysics Data System (ADS)

    Shimizu, Masahiro; Mitsui, Katsuyoshi; Inuishi, Masahide; Arima, Hideaki; Hamaguchi, Chihiro

    1998-12-01

    In this paper an experimental study of the scalability of a gate/N- overlapped lightly doped drain (OL-LDD) structure in the deep-submicrometer regime is presented. Devices were optimized for processes with a design rule down to 0.15 µm. The allowable power supply voltage is obtained by investigating the time-dependent dielectric breakdown reliability, the minimum operating voltage, the gate-induced-drain-leakage current, the drain-induced-barrier-lowering effect and the DC hot carrier reliability. It was found that the maximum allowable supply voltage is mainly limited by the DC hot carrier reliability even in the deep-submicrometer range. A higher current-driving ability in the OL-LDD structure is achieved in comparison to that in a single drain (SD) structure when VDmax is applied as a supply voltage. The OL-LDD structure has a smaller CGD in the inversion region as well as in the accumulated region, as compared with the SD structure, especially with smaller LG. Consequently, the performance of complementary metal-oxide-semiconductor (CMOS) devices with the OL-LDD structure is superior to that with the SD structure in the deep-submicrometer regime. It is also confirmed that the OL-LDD structure has a scaling merit even for 0.15 µm CMOS devices.

  14. Nifedipine prevents sodium caprate-induced barrier dysfunction in human epidermal keratinocyte cultures.

    PubMed

    Uchino, Yoshihiro; Matsumoto, Junichi; Watanabe, Takuya; Hamabashiri, Masato; Tsuchiya, Takashi; Kimura, Ikuya; Yamauchi, Atsushi; Kataoka, Yasufumi

    2015-01-01

    Tight junctions (TJs) of the epidermis play an important role in maintaining the epidermal barrier. TJ breakdown is associated with skin problems, such as wrinkles and transepidermal water loss (TEWL). Clinical studies have reported that topical nifedipine is effective in reducing the depth of wrinkles and improving TEWL. However, it remains unknown whether nifedipine influences the TJ function in the epidermis. In the present study, we investigated the effect of nifedipine on epidermal barrier dysfunction in normal human epidermal keratinocytes (NHEKs) treated with sodium caprate (C10), a TJ inhibitor. Nifedipine reversed the C10-decreased transepithelial electrical resistance values as a measure of disruption of the epidermal barrier. Immunocytochemical observations revealed that nifedipine improved the C10-induced irregular arrangement of claudin-1, a key protein in TJs. Taken together, these findings suggest that nifedipine prevents epidermal barrier dysfunction, at least in part, by reconstituting the irregular claudin-1 localization at TJs in C10-treated NHEKs. PMID:26027835

  15. Enteropathogenic E. coli-induced barrier function alteration is not a consequence of host cell apoptosis

    PubMed Central

    Viswanathan, V. K.; Weflen, Andrew; Koutsouris, Athanasia; Roxas, Jennifer L.; Hecht, Gail

    2012-01-01

    Enteropathogenic Escherichia coli (EPEC) is a diarrheagenic pathogen that perturbs intestinal epithelial function. Many of the alterations in the host cells are mediated by effector molecules that are secreted directly into epithelial cells by the EPEC type III secretion system. The secreted effector molecule EspF plays a key role in redistributing tight junction proteins and altering epithelial barrier function. EspF has also been shown to localize to mitochondria and trigger membrane depolarization and eventual host cell death. The relationship, if any, between EspF-induced host cell death and epithelial barrier disruption is presently not known. Site-directed mutation of leucine 16 (L16E) of EspF impairs both mitochondrial localization and consequent host cell death. Although the mutation lies within a region critical for type III secretion, EspF(L16E) is secreted efficiently from EPEC. Despite its inability to promote cell death, EspF(L16E) was not impaired for tight junction alteration or barrier disruption. Consistent with this, the pan-caspase inhibitor Q-VD-OPH, despite reducing EPEC-induced host cell death, had no effect on infection-mediated barrier function alteration. Thus EPEC alters the epithelial barrier independent of its ability to induce host cell death. PMID:18356531

  16. NITROTYROSINATION OF A TUBULIN INDUCES EPITHELIAL BARRIER DYSFUNCTION

    EPA Science Inventory

    Nitrotyrosination of a-Tubulin Induces Epithelial Transport Dysfunction. Yuh-Chin Huang, Lisa Dailey, Wen-Li Zhang and Ilona Jaspers. ORD, Environmental Protection Agency and CEMLB, University of North Carolina

    a-Tubulin undergoes a cyclic removal and readdition of tyrosin...

  17. Ensemble Monte Carlo particle investigation of hot electron induced source-drain burnout characteristics of GaAs field-effect transistors

    NASA Astrophysics Data System (ADS)

    Moglestue, C.; Buot, F. A.; Anderson, W. T.

    1995-08-01

    The lattice heating rate has been calculated for GaAs field-effect transistors of different source-drain channel design by means of the ensemble Monte Carlo particle model. Transport of carriers in the substrate and the presence of free surface charges are also included in our simulation. The actual heat generation was obtained by accounting for the energy exchanged with the lattice of the semiconductor during phonon scattering. It was found that the maximum heating rate takes place below the surface near the drain end of the gate. The results correlate well with a previous hydrodynamic energy transport estimate of the electronic energy density, but shifted slightly more towards the drain. These results further emphasize the adverse effects of hot electrons on the Ohmic contacts.

  18. TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes.

    PubMed

    Jiang, Feng; Chen, Qingzhong; Huang, Liming; Wang, Ying; Zhang, Zhuhong; Meng, Xiangda; Liu, Yuanyuan; Mao, Chunjie; Zheng, Fang; Zhang, Jingkai; Yan, Hua

    2016-01-01

    Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p < 0.001), and then increased three months later and thereafter. TNFSF15 treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies. PMID:27120595

  19. Low Barrier Carbon Induced CO Dissociation on Stepped Cu.

    PubMed

    Ng, M L; Abild-Pedersen, F; Kaya, S; Mbuga, F; Ogasawara, H; Nilsson, A

    2015-06-19

    Using x-ray photoelectron spectroscopy we observe the breaking of the strong interatomic bond in molecular CO at low temperature on a stepped Cu surface. Since the electronic structure of Cu does not allow for the splitting of CO at such low temperatures it suggests that there may be a less obvious pathway for the process. Through x-ray photoelectron spectroscopy we can clearly identify products associated with the dissociation of CO and the subsequent formation of stable graphitic carbon on the surface. However, the dissociation of CO can be inhibited when the stepped Cu surface is kept clean from surface carbon. These observations imply that the reaction is driven by the presence of small amounts of weakly bound carbon at the surface. Density-functional theory calculations confirm that carbon atoms on a stepped Cu surface indeed are the preferred adsorption sites for CO, which increases the stabilization of CO on the surface and weakens the C-O bond. This results in the breaking of the C-O bond at the step edge via the Boudouard reaction (2CO(ads)→C(ads)+CO(2)) with a barrier of 0.71 eV. PMID:26196988

  20. TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes

    PubMed Central

    Jiang, Feng; Chen, Qingzhong; Huang, Liming; Wang, Ying; Zhang, Zhuhong; Meng, Xiangda; Liu, Yuanyuan; Mao, Chunjie; Zheng, Fang; Zhang, Jingkai; Yan, Hua

    2016-01-01

    Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p < 0.001), and then increased three months later and thereafter. TNFSF15 treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies. PMID:27120595

  1. Low Barrier Carbon Induced CO Dissociation on Stepped Cu

    NASA Astrophysics Data System (ADS)

    Ng, M. L.; Abild-Pedersen, F.; Kaya, S.; Mbuga, F.; Ogasawara, H.; Nilsson, A.

    2015-06-01

    Using x-ray photoelectron spectroscopy we observe the breaking of the strong interatomic bond in molecular CO at low temperature on a stepped Cu surface. Since the electronic structure of Cu does not allow for the splitting of CO at such low temperatures it suggests that there may be a less obvious pathway for the process. Through x-ray photoelectron spectroscopy we can clearly identify products associated with the dissociation of CO and the subsequent formation of stable graphitic carbon on the surface. However, the dissociation of CO can be inhibited when the stepped Cu surface is kept clean from surface carbon. These observations imply that the reaction is driven by the presence of small amounts of weakly bound carbon at the surface. Density-functional theory calculations confirm that carbon atoms on a stepped Cu surface indeed are the preferred adsorption sites for CO, which increases the stabilization of CO on the surface and weakens the C-O bond. This results in the breaking of the C-O bond at the step edge via the Boudouard reaction (2 COads→Cads+CO2 ) with a barrier of 0.71 eV.

  2. Current-induced changes of migration energy barriers in graphene and carbon nanotubes.

    PubMed

    Obodo, J T; Rungger, I; Sanvito, S; Schwingenschlögl, U

    2016-05-21

    An electron current can move atoms in a nanoscale device with important consequences for the device operation and breakdown. We perform first principles calculations aimed at evaluating the possibility of changing the energy barriers for atom migration in carbon-based systems. In particular, we consider the migration of adatoms and defects in graphene and carbon nanotubes. Although the current-induced forces are large for both the systems, in graphene the force component along the migration path is small and therefore the barrier height is little affected by the current flow. In contrast, the same barrier is significantly reduced in carbon nanotubes as the current increases. Our work also provides a real-system numerical demonstration that current-induced forces within density functional theory are non-conservative. PMID:27127889

  3. Dielectric barrier discharge plasma induced degradation of aqueous atrazine.

    PubMed

    Feng, Jingwei; Jiang, Lin; Zhu, Dan; Su, Kuizu; Zhao, Dayong; Zhang, Jibiao; Zheng, Zheng

    2016-05-01

    Degradation of herbicide atrazine in aqueous solution was investigated using a plate type dielectric barrier discharge (DBD) plasma reactor. DBD plasma was generated at the gas-liquid interface of the formed water film. At discharge time of 14 min, atrazine was degradated effectively with a degradation rate of 99 % at the discharge power of 200 W. The experimental data fitted well with first-order kinetics and the energy efficiency for 90 % degradation of atrazine (G value) was calculated, obtaining a rate constant of 0.35 min(-1) and a G value of 1.27 × 10(-10) mol J(-1) (98.76 mg kW(-1) h(-1)) at a discharge power of 200 W, respectively. The addition of Fe(2+) increased the rate constant and G value dramatically, and a significant decrease of the rate constant and G value was observed with the addition of radical scavengers (tert-butyl alcohol, isopropyl alcohol, or Na2CO3). The generated aqueous O3 and H2O2 were determined, which promoted the degradation of herbicide atrazine. Dechlorination was observed and the experimentally detected Cl(-) was 1.52 mg L(-1) at a discharge time of 14 min. The degradation intermediates of atrazine were detected by means of liquid chromatography-mass spectrometry; dechlorination, hydroxylation, dealkylation, and alkyl oxidation processes were involved in the degradation pathways of atrazine. PMID:26832879

  4. Current-induced changes of migration energy barriers in graphene and carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Obodo, J. T.; Rungger, I.; Sanvito, S.; Schwingenschlögl, U.

    2016-05-01

    An electron current can move atoms in a nanoscale device with important consequences for the device operation and breakdown. We perform first principles calculations aimed at evaluating the possibility of changing the energy barriers for atom migration in carbon-based systems. In particular, we consider the migration of adatoms and defects in graphene and carbon nanotubes. Although the current-induced forces are large for both the systems, in graphene the force component along the migration path is small and therefore the barrier height is little affected by the current flow. In contrast, the same barrier is significantly reduced in carbon nanotubes as the current increases. Our work also provides a real-system numerical demonstration that current-induced forces within density functional theory are non-conservative.An electron current can move atoms in a nanoscale device with important consequences for the device operation and breakdown. We perform first principles calculations aimed at evaluating the possibility of changing the energy barriers for atom migration in carbon-based systems. In particular, we consider the migration of adatoms and defects in graphene and carbon nanotubes. Although the current-induced forces are large for both the systems, in graphene the force component along the migration path is small and therefore the barrier height is little affected by the current flow. In contrast, the same barrier is significantly reduced in carbon nanotubes as the current increases. Our work also provides a real-system numerical demonstration that current-induced forces within density functional theory are non-conservative. Electronic supplementary information (ESI) available. See DOI: 10.1039/C6NR00534A

  5. Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo.

    PubMed

    Lee, Wonhwa; Yoo, Hayoung; Kim, Jeong Ah; Lee, Sangkyu; Jee, Jun-Goo; Lee, Min Young; Lee, You-Mie; Bae, Jong-Sup

    2013-08-01

    Piperlonguminine (PL), an important component of Piper longum fruits, is well known to possess potent anti-hyperlipidemic, anti-platelet and anti-melanogenesis activities. In this study, we first investigated the possible barrier protective effects of piperlonguminine against proinflammatory responses induced by lipopolysaccharide (LPS) and the associated signaling pathways in vitro and in vivo. The barrier protective activities of PL were determined by measuring permeability, monocytes adhesion and migration, and activation of proinflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and in mice. We found that PL inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of monocytes to human endothelial cells. PL also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Further studies revealed that PL suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with PL resulted in reduced LPS-induced septic mortality. Collectively, these results suggest that PL protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. PMID:23619565

  6. Regulation of Thrombin-Induced Lung Endothelial Cell Barrier Disruption by Protein Kinase C Delta

    PubMed Central

    Xie, Lishi; Chiang, Eddie T.; Kelly, Gabriel T.; Kanteti, Prasad; Singleton, Patrick A.; Camp, Sara M.; Zhou, Tingting; Dudek, Steven M.; Natarajan, Viswanathan; Wang, Ting; Black, Steven M.; Garcia, Joe G. N.; Jacobson, Jeffrey R.

    2016-01-01

    Protein Kinase C (PKC) plays a significant role in thrombin-induced loss of endothelial cell (EC) barrier integrity; however, the existence of more than 10 isozymes of PKC and tissue–specific isoform expression has limited our understanding of this important second messenger in vascular homeostasis. In this study, we show that PKCδ isoform promotes thrombin-induced loss of human pulmonary artery EC barrier integrity, findings substantiated by PKCδ inhibitory studies (rottlerin), dominant negative PKCδ construct and PKCδ silencing (siRNA). In addition, we identified PKCδ as a signaling mediator upstream of both thrombin-induced MLC phosphorylation and Rho GTPase activation affecting stress fiber formation, cell contraction and loss of EC barrier integrity. Our inhibitor-based studies indicate that thrombin-induced PKCδ activation exerts a positive feedback on Rho GTPase activation and contributes to Rac1 GTPase inhibition. Moreover, PKD (or PKCμ) and CPI-17, two known PKCδ targets, were found to be activated by PKCδ in EC and served as modulators of cytoskeleton rearrangement. These studies clarify the role of PKCδ in EC cytoskeleton regulation, and highlight PKCδ as a therapeutic target in inflammatory lung disorders, characterized by the loss of barrier integrity, such as acute lung injury and sepsis. PMID:27442243

  7. High glucose induces dysfunction of airway epithelial barrier through down-regulation of connexin 43.

    PubMed

    Yu, Hongmei; Yang, Juan; Zhou, Xiangdong; Xiao, Qian; Lü, Yang; Xia, Li

    2016-03-01

    The airway epithelium is a barrier to the inhaled antigens and pathogens. Connexin 43 (Cx43) has been found to play critical role in maintaining the function of airway epithelial barrier and be involved in the pathogenesis of the diabetic retinal vasculature, diabetes nephropathy and diabetes skin. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that the down-regulation of Cx43 induced by HG alters the expression of tight junctions (zonula occludens-1 (ZO-1) and occludin) and contributes to dysfunction of airway epithelial barrier, and Cx43 plays a critical role in the process in human airway epithelial cells (16 HBE). We show that high glucose (HG) decreased the expression of ZO-1 and occludin, disassociated interaction between Cx43 and tight junctions, and then increased airway epithelial transepithelial electrical resistance (TER) and permeability by down-regulation of Cx43 in human airway epithelial cells. These observations demonstrate an important role for Cx43 in regulating HG-induced dysfunction of airway epithelial barrier. These findings may bring new insights into the molecular pathogenesis of pulmonary infection related to diabetes mellitus and lead to novel therapeutic intervention for the dysfunction of airway epithelial barrier in chronic inflammatory airway diseases. PMID:26902399

  8. Barrier-induced chaos in a kicked rotor: Classical subdiffusion and quantum localization

    NASA Astrophysics Data System (ADS)

    Paul, Sanku; Pal, Harinder; Santhanam, M. S.

    2016-06-01

    The relation between classically chaotic dynamics and quantum localization is studied in a system that violates the assumptions of the Kolmogorov-Arnold-Moser (KAM) theorem, namely, the kicked rotor in a discontinuous potential barrier. We show that the discontinuous barrier induces chaos and more than two distinct subdiffusive energy growth regimes, the latter being an unusual feature for Hamiltonian chaos. We show that the dynamical localization in the quantized version of this system carries the imprint of non-KAM classical dynamics through the dependence of quantum break time on subdiffusion exponents. We briefly comment on the experimental feasibility of this system.

  9. Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects

    PubMed Central

    MacRedmond, Ruth E.; Singhera, Gurpreet K.; Wadsworth, Samuel J.; Attridge, Susan; Bahzad, Mohammed; Williams, Kristy; Coxson, Harvey O.; White, Steven R.; Dorscheid, Delbert R.

    2014-01-01

    Objective The airway epithelium has a number of roles pivotal to the pathogenesis of asthma, including provision of a physical and immune barrier to the inhaled environment. Dysregulated injury and repair responses in asthma result in loss of airway epithelial integrity. Inhaled corticosteroids are a corner stone of asthma treatment. While effective in controlling asthma symptoms, they fail to prevent airway remodeling. Direct cytopathic effects on the airway epithelium may contribute to this. Methods This study examined the effects of a 4-week treatment regimen of inhaled fluticasone 500 μg twice daily in healthy human subjects. Induced sputum was collected for cell counts and markers of inflammation. Barrier function was examined by diethylenetriaminepentacetic acid (DTPA) clearance measured by nuclear scintillation scan, and albumin concentration in induced sputum. Results Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum. There was no change in airway inflammation by induced sputum inflammatory cell counts or cytokine levels. Epithelial shedding was associated with an increase in barrier function, as measured by both a decrease in DTPA clearance and decreased albumin in induced sputum. This likely reflects the normal repair response. Conclusion Inhaled corticosteroids cause injury to normal airway epithelium. These effects warrant further evaluation in asthma, where the dysregulated repair response may contribute to airway remodeling. PMID:25324978

  10. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    PubMed

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID:26551768

  11. The Na+/H+ exchange inhibitor HOE642 prevents stress-induced epithelial barrier dysfunction.

    PubMed

    Nowak, Peter; Blaheta, Roman; Schuller, Alina; Cinatl, Jindrich; Wimmer-Greinecker, Gerhard; Moritz, Anton; Scholz, Martin

    2004-08-01

    Recently, evidence has been obtained that the Na+/H+ exchange (NHE) inhibitor HOE642 may stabilize endothelial and epithelial barrier function in vivo. However, the underlying mechanisms are not known. Therefore, we studied the influence of HOE642 on the barrier function of the epithelial cell line CaCo2. The phorbolester phorbol 12-myristate 13-acetate (PMA) was used to induce hyperpermeability of the epithelial layer which was indirectly determined by measuring the transepithelial electrical resistance (TER). Confocal laser scan microscopy (LSM) served to analyze the intracellular localization of adherens and tight junction molecules. In five independent experiments we found that HOE642 increased TER in non-treated CaCo2 cells (control: 350 +/- 28 Omega/cm2; HOE642: 444 +/- 53 Omega/cm2) and prevented PMA-induced barrier dysfunction (PMA: 33 +/- 12 Omega/cm2; PMA plus HOE642: 496 +/- 47 Omega/cm2). LSM showed that HOE642 prevented the PMA-induced disassociation of the zonula adherens molecule beta-catenin from the cell membrane and the decreased expression of the zonula occludens molecule ZO-1. From our data we conclude that HOE642 may prevent stress-induced epithelial dysfunction by stabilization of cell membrane-associated junction molecules. PMID:15254761

  12. Ultraviolet B-induced alterations of the skin barrier and epidermal calcium gradient.

    PubMed

    Jiang, Shao Jun; Chu, Ai Wu; Lu, Zhen Feng; Pan, Min Hong; Che, Dun Fa; Zhou, Xiao Jun

    2007-12-01

    Ultraviolet irradiation induces a variety of cutaneous changes, including epidermal permeability barrier disruption. In the present study, we assessed the effects of ultraviolet B (UVB) irradiation in epidermal barrier function and calcium distribution in murine epidermis. Adult hairless mice were exposed to a single dose of UVB (0.15 J/cm(2)). Barrier function was evaluated by transepidermal water loss (TEWL), lanthanum perfusion. The morphological alterations were examined by histology, immunohistochemistry and electron microscopy using ruthenium tetroxide (RuO(4)) postfixation. For evaluation of the effect on epidermal calcium distribution, the ion-capture cytochemistry was employed. UVB irradiation caused a significant increase in TEWL, which peaked at day 4. In parallel, the increased number of sunburn cells and the changes in epidermal hyperplasia and proliferation were observed. Electron microscopic observation demonstrated that the water-soluble lanthanum tracer was present in the extracellular stratum corneum domains, and the increased intercellular permeability was correlated with defective organization of the extracellular lipid lamellar bilayers of the stratum corneum. Moreover, UVB irradiation also caused an appearance of calcium precipitates in the stratum corneum and transitional cell layers as well as the increased cytosolic calcium in the lower epidermis, reflecting the alterations of the epidermal calcium gradient. These results suggest that the changes of the epidermal calcium distribution pattern may correlate with the perturbation of the epidermal barrier induced by UVB irradiation. PMID:18031457

  13. Protein tyrosine kinase 6 mediates TNFα-induced endothelial barrier dysfunction

    PubMed Central

    Haines, RJ; Beard, RS; Wu, MH

    2014-01-01

    A key event in the progression of systemic inflammation resulting from severe trauma or shock involves microvascular hyperpermeability, which leads to excessive plasma fluid and proteins accumulating in extravascular space resulting in tissue edema. The precise molecular mechanism of the hyperpermeability response is not completely understood. Protein tyrosine kinase 6 (PTK6, also known as breast tumor kinase BRK) is a non-receptor tyrosine kinase related to Src-family proteins. Although it has also been shown that PTK6 participates in regulating epithelial barrier function, the role of PTK6 in endothelial barrier function has not been reported. In this study, we hypothesized that PTK6 is 1) expressed in vascular endothelial cells, and 2) contributes to vascular endothelial hyperpermeability in response to TNFα. Results showed that PTK6 was detected in mouse endothelial cells at the level of protein and mRNA. In addition, PTK6 knockdown attenuated TNFα induced decrease in endothelial barrier function as measured by electric cell-substrate impedance sensing (ECIS) and in vitro transwell albumin-flux assays. Furthermore, we showed that TNFα treatment of endothelial cells increased active PTK6 association with p120-catenin at endothelial cell-cell junctions. Further analysis using immunocytochemistry and immunoprecipitation demonstrated that PTK6 knockdown attenuated TNFα induced VE-cadherin internalization as well as promoting its association with p120-catenin. Our study demonstrates a novel role of PTK6 in mediating endothelial barrier dysfunction. PMID:25446122

  14. p53 protects against LPS-induced lung endothelial barrier dysfunction

    PubMed Central

    Dimitropoulou, Christiana; Birmpas, Charalampos; Joshi, Atul; Thangjam, Gagan; Catravas, John D.

    2015-01-01

    New therapies toward heart and blood vessel disorders may emerge from the development of Hsp90 inhibitors. Several independent studies suggest potent anti-inflammatory activities of those agents in human tissues. The molecular mechanisms responsible for their protective effects in the vasculature remain unclear. The present study demonstrates that the transcription factor p53, an Hsp90 client protein, is crucial for the maintenance of vascular integrity, protects again LPS-induced endothelial barrier dysfunction, and is involved in the mediation of the anti-inflammatory activity of Hsp90 inhibitors in lung tissues. p53 silencing by siRNA decreased transendothelial resistance (a measure of endothelial barrier function). A similar effect was induced by the p53 inhibitor pifithrin, which also potentiated the LPS-induced hyperpermeability in human lung microvascular endothelial cells (HLMVEC). On the other hand, p53 induction by nutlin suppressed the LPS-induced vascular barrier dysfunction. LPS decreased p53 expression in lung tissues and that effect was blocked by pretreatment with Hsp90 inhibitors both in vivo and in vitro. Furthermore, the Hsp90 inhibitor 17-allyl-amino-demethoxy-geldanamycin suppressed the LPS-induced overexpression of the p53 negative regulator MDMX as well as p53 and MDM2 (another p53 negative regulator) phosphorylation in HLMVEC. Both negative p53 regulators were downregulated by LPS in vivo. Chemically induced p53 overexpression resulted in the suppression of LPS-induced RhoA activation and MLC2 phosphorylation, whereas p53 suppression caused the opposite effects. These observations reveal new mechanisms for the anti-inflammatory actions of Hsp90 inhibitors, i.e., the induction of the transcription factor p53, which in turn can orchestrate robust vascular anti-inflammatory responses both in vivo and in vitro. PMID:25713322

  15. Cyclic stretch induces alveolar epithelial barrier dysfunction via calpain-mediated degradation of p120-catenin.

    PubMed

    Wang, Yuelan; Minshall, Richard D; Schwartz, David E; Hu, Guochang

    2011-08-01

    Lung hyperinflation is known to be an important contributing factor in the pathogenesis of ventilator-induced lung injury. Mechanical stretch causes epithelial barrier dysfunction and an increase in alveolar permeability, although the precise mechanisms have not been completely elucidated. p120-catenin is an adherens junction-associated protein that regulates cell-cell adhesion. In this study, we determined the role of p120-catenin in cyclic stretch-induced alveolar epithelial barrier dysfunction. Cultured alveolar epithelial cells (MLE-12) were subjected to uniform cyclic (0.5 Hz) biaxial stretch from 0 to 8 or 20% change in surface area for 0, 1, 2, or 4 h. At the end of the experiments, cells were lysed to determine p120-catenin expression by Western blot analysis. Immunofluorescence staining of p120-catenin and F-actin was performed to assess the integrity of monolayers and interepithelial gap formation. Compared with unstretched control cells, 20% stretch caused a significant loss in p120-catenin expression, which was coupled to interepithelial gap formation. p120-Catenin knockdown with small interfering RNA (siRNA) dose dependently increased stretch-induced gap formation, whereas overexpression of p120-catenin abolished stretch-induced gap formation. Furthermore, pharmacological calpain inhibition or depletion of calpain-1 with a specific siRNA prevented p120-catenin loss and subsequent stretch-induced gap formation. Our findings demonstrate that p120-catenin plays a critical protective role in cyclic stretch-induced alveolar barrier dysfunction, and, thus, maintenance of p120-catenin expression may be a novel therapeutic strategy for the prevention and treatment of ventilator-induced lung injury. PMID:21571907

  16. A multitheragnostic nanobubble system to induce blood-brain barrier disruption with magnetically guided focused ultrasound.

    PubMed

    Huang, Hsin-Yang; Liu, Hao-Li; Hsu, Po-Hung; Chiang, Chih-Sheng; Tsai, Chih-Hung; Chi, Huei-Shang; Chen, San-Yuan; Chen, You-Yin

    2015-01-27

    A novel magnetically guidable nanobubble is designed for disrupting the blood-brain barrier (BBB) by combining magnetic guidance with focused ultrasound in vivo. The magnetic-nanobubble platform also demonstrates the potential to serve as a unique theranostic tool via performing focused ultrasound (FUS)-induced BBB disruption and magnetic resonance imaging (MRI)/ultrasound dual-modality contrast-agent imaging to improve the drug delivery of therapeutic substances or gene therapy into the central nervous system. PMID:25472627

  17. Cluster Model for Near-barrier Fusion Induced by Weakly Bound and Halo Nuclei

    SciTech Connect

    Beck, C.; Keeley, N.

    2008-05-12

    The influence on the fusion process of coupling transfer/breakup channels is investigated for the medium weight {sup 6,7}Li+{sup 59}Co systems in the vicinity of the Coulomb barrier. Coupling effects are discussed within a comparison of predictions of the Continuum Discretized Coupled-Channels model. Applications to {sup 6}He+{sup 59}Co induced by the borromean halo nucleus {sup 6}He are also proposed.

  18. Near-barrier Fusion Induced by Stable Weakly Bound and Exotic Halo Light Nuclei

    SciTech Connect

    Beck, C.; Zafra, A. Sanchez I.; Diaz-Torres, A.; Thompson, I. J.; Keeley, N.

    2006-08-14

    The effect of breakup is investigated for the medium weight 6Li+59Co system in the vicinity of the Coulomb barrier. The strong coupling of breakup/transfer channels to fusion is discussed within a comparison of predictions of the Continuum Discretized Coupled-Channels model which is also applied to 6He+59Co a reaction induced by the borromean halo nucleus 6He.

  19. Myeloperoxidase-Derived Oxidants Induce Blood-Brain Barrier Dysfunction In Vitro and In Vivo

    PubMed Central

    Üllen, Andreas; Singewald, Evelin; Konya, Viktoria; Fauler, Günter; Reicher, Helga; Nusshold, Christoph; Hammer, Astrid; Kratky, Dagmar; Heinemann, Akos; Holzer, Peter; Malle, Ernst; Sattler, Wolfgang

    2013-01-01

    Peripheral leukocytes can exacerbate brain damage by release of cytotoxic mediators that disrupt blood-brain barrier (BBB) function. One of the oxidants released by activated leukocytes is hypochlorous acid (HOCl) formed via the myeloperoxidase (MPO)-H2O2-Cl− system. In the present study we examined the role of leukocyte activation, leukocyte-derived MPO and MPO-generated oxidants on BBB function in vitro and in vivo. In a mouse model of lipopolysaccharide (LPS)-induced systemic inflammation, neutrophils that had become adherent released MPO into the cerebrovasculature. In vivo, LPS-induced BBB dysfunction was significantly lower in MPO-deficient mice as compared to wild-type littermates. Both, fMLP-activated leukocytes and the MPO-H2O2-Cl− system inflicted barrier dysfunction of primary brain microvascular endothelial cells (BMVEC) that was partially rescued with the MPO inhibitor 4-aminobenzoic acid hydrazide. BMVEC treatment with the MPO-H2O2-Cl− system or activated neutrophils resulted in the formation of plasmalogen-derived chlorinated fatty aldehydes. 2-chlorohexadecanal (2-ClHDA) severely compromised BMVEC barrier function and induced morphological alterations in tight and adherens junctions. In situ perfusion of rat brain with 2-ClHDA increased BBB permeability in vivo. 2-ClHDA potently activated the MAPK cascade at physiological concentrations. An ERK1/2 and JNK antagonist (PD098059 and SP600125, respectively) protected against 2-ClHDA-induced barrier dysfunction in vitro. The current data provide evidence that interference with the MPO pathway could protect against BBB dysfunction under (neuro)inflammatory conditions. PMID:23691142

  20. HMGB1 induces human lung endothelial cell cytoskeletal rearrangement and barrier disruption.

    PubMed

    Wolfson, Rachel K; Chiang, Eddie T; Garcia, Joe G N

    2011-03-01

    Acute lung injury (ALI) results from loss of alveolar-capillary barrier integrity and the evolution of high-permeability pulmonary edema resulting in alveolar flooding and significant morbidity and mortality. HMGB1 is a late mediator of sepsis which uniquely participates in the evolution of sepsis and sepsis-induced ALI. The molecular events by which HMGB1 contributes to ALI remain poorly characterized. We characterized the role of HMGB1 in endothelial cell (EC) cytoskeletal rearrangement and vascular permeability, events essential to paracellular gap formation and barrier dysfunction characteristic of ALI. Initial experiments demonstrated HMGB1-mediated dose-dependent (5-20 μg/ml) decreases in transendothelial cell electrical resistance (TER) in the human pulmonary artery EC, a reflection of loss of barrier integrity. Furthermore, HMGB1 produced dose-dependent increases in paracellular gap formation in concert with loss of peripheral organized actin fibers, dissociation of cell-cell junctional cadherins, and the development of central stress fibers, a phenotypic change associated with increased contractile activity and increased EC permeability. Using siRNA strategies directed against known HMGB1 receptors (RAGE, TLR2, TLR4), we systematically determined that the receptor for advanced glycation end products (RAGE) is the primary receptor signaling HMGB1-induced TER decreases and paracellular gap formation via p38 MAP kinase activation and phosphorylation of the actin-binding protein, Hsp27. These studies add to the understanding of HMGB1-induced inflammatory events and vascular barrier disruption and offer the potential for clinical intervention in sepsis-induced ALI. PMID:21146549

  1. Studies of near-barrier fusion induced by neutron-rich nuclei at HRIBF

    SciTech Connect

    Liang, J Felix

    2011-01-01

    Fusion induced by neutron-rich radioactive beams is a topic of current interest. The findings will be useful for using radioactive beams to produce superheavy elements. Results from recent measurements performed with neutron-rich radioactive Sn and Te beams are presented. Coupled-channels calculations were carried out to study the observed sub-barrier fusion enhancement. The fusion probability in Sn on Ni were probed by comparing the evaporation residue cross sections at high excitation energies.

  2. Edge-induced Schottky barrier modulation at metal contacts to exfoliated molybdenum disulfide flakes

    NASA Astrophysics Data System (ADS)

    Nouchi, Ryo

    2016-08-01

    Ultrathin two-dimensional semiconductors obtained from layered transition-metal dichalcogenides such as molybdenum disulfide (MoS2) are promising for ultimately scaled transistors beyond Si. Although the shortening of the semiconductor channel is widely studied, the narrowing of the channel, which should also be important for scaling down the transistor, has been examined to a lesser degree thus far. In this study, the impact of narrowing on mechanically exfoliated MoS2 flakes was investigated according to the channel-width-dependent Schottky barrier heights at Cr/Au contacts. Narrower channels were found to possess a higher Schottky barrier height, which is ascribed to the edge-induced band bending in MoS2. The higher barrier heights degrade the transistor performance as a higher electrode-contact resistance. Theoretical analyses based on Poisson's equation showed that the edge-induced effect can be alleviated by a high dopant impurity concentration, but this strategy should be limited to channel widths of roughly 0.7 μm because of the impurity-induced charge-carrier mobility degradation. Therefore, proper termination of the dangling bonds at the edges should be necessary for aggressive scaling with layered semiconductors.

  3. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon

    PubMed Central

    Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J.; Dekker, Jan; van Mil, Saskia W. C.; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof

    2015-01-01

    Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function. PMID:26216954

  4. Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon.

    PubMed

    Ijssennagger, Noortje; Belzer, Clara; Hooiveld, Guido J; Dekker, Jan; van Mil, Saskia W C; Müller, Michael; Kleerebezem, Michiel; van der Meer, Roelof

    2015-08-11

    Colorectal cancer risk is associated with diets high in red meat. Heme, the pigment of red meat, induces cytotoxicity of colonic contents and elicits epithelial damage and compensatory hyperproliferation, leading to hyperplasia. Here we explore the possible causal role of the gut microbiota in heme-induced hyperproliferation. To this end, mice were fed a purified control or heme diet (0.5 μmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme-induced hyperproliferation was shown to depend on the presence of the gut microbiota, because hyperproliferation was completely eliminated by antibiotics, although heme-induced luminal cytotoxicity was sustained in these mice. Colon mucosa transcriptomics revealed that antibiotics block heme-induced differential expression of oncogenes, tumor suppressors, and cell turnover genes, implying that antibiotic treatment prevented the heme-dependent cytotoxic micelles to reach the epithelium. Our results indicate that this occurs because antibiotics reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin-degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds and can drive mucin denaturation and microbial access to the mucus layer. This reduction results in formation of trisulfides that can be detected in vitro and in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis and thus as a proxy for mucus barrier reduction. In feces, antibiotics drastically decreased trisulfides but increased mucin polymers that can be lysed by sulfide. We conclude that the gut microbiota is required for heme-induced epithelial hyperproliferation and hyperplasia because of the capacity to reduce mucus barrier function. PMID:26216954

  5. Stress-induced changes in skin barrier function in healthy women.

    PubMed

    Altemus, M; Rao, B; Dhabhar, F S; Ding, W; Granstein, R D

    2001-08-01

    Despite clear exacerbation of several skin disorders by stress, the effect of psychologic or exertional stress on human skin has not been well studied. We investigated the effect of three different stressors, psychologic interview stress, sleep deprivation, and exercise, on several dermatologic measures: transepidermal water loss, recovery of skin barrier function after tape stripping, and stratum corneum water content (skin conductance). We simultaneously measured the effects of stress on plasma levels of several stress-response hormones and cytokines, natural killer cell activity, and absolute numbers of peripheral blood leukocytes. Twenty-five women participated in a laboratory psychologic interview stress, 11 women participated in one night of sleep deprivation, and 10 women participated in a 3 d exercise protocol. The interview stress caused a delay in the recovery of skin barrier function, as well as increases in plasma cortisol, norepinephrine, interleukin-1beta and interleukin-10, tumor necrosis factor-alpha, and an increase in circulating natural killer cell activity and natural killer cell number. Sleep deprivation also decreased skin barrier function recovery and increased plasma interleukin-1beta, tumor necrosis factor-alpha, and natural killer cell activity. The exercise stress did not affect skin barrier function recovery, but caused an increase in natural killer cell activity and circulating numbers of both cytolytic T lymphocytes and helper T cells. In addition, cytokine responses to the interview stress were inversely correlated with changes in barrier function recovery. These results suggest that acute psychosocial and sleep deprivation stress disrupts skin barrier function homeostasis in women, and that this disruption may be related to stress-induced changes in cytokine secretion. PMID:11511309

  6. Field-induced macroscopic barrier model for persistent photoconductivity in nanocrystalline oxide thin-film transistors

    NASA Astrophysics Data System (ADS)

    Choi, Hyun-Sik; Jeon, Sanghun

    2014-03-01

    Persistent photoconductivity (PPC) in nanocrystalline InZnO thin-film transistors (TFTs) was studied using carrier fluctuation measurements and transient analysis. Low-frequency noise measurements and decay kinetics indicate that the band bending by the external field together with the ionized oxygen vacancy (Vo++) generated during the light exposure is the main cause of the PPC phenomenon. Based on these observations, a field-induced macroscopic barrier model is proposed as the origin of PPC for InZnO TFTs. In particular, this model explains that the carrier separation between e and Vo++ is induced by the external field applied to the three electrodes inside the transistor.

  7. NOVEL ATYPICAL PKC INHIBITORS PREVENT VASCULAR ENDOTHELIAL GROWTH FACTOR-INDUCED BLOOD-RETINAL BARRIER DYSFUNCTION

    PubMed Central

    Titchenell, Paul M.; Lin, Cheng-Mao; Keil, Jason M.; Sundstrom, Jeffrey M.; Smith, Charles D.; Antonetti, David A.

    2013-01-01

    SYNOPSIS Pro-inflammatory cytokines and growth factors such as vascular endothelial growth factor (VEGF) contribute to the loss of the blood-retinal barrier (BRB) and subsequent macular edema in various retinal pathologies. VEGF signaling requires conventional PKC (PKCβ) activity; however, PKCβ inhibition only partially prevents VEGF-induced endothelial permeability and does not affect pro-inflammatory cytokine-induced permeability suggesting the involvement of alternative signaling pathways. Here, we provide evidence for the involvement of atypical protein kinase C (aPKC) signaling in VEGF-induced endothelial permeability and identify a novel class of inhibitors of aPKC that prevent BRB breakdown in vivo. Genetic and pharmacological manipulations of aPKC isoforms were used to assess their contribution to endothelial permeability in culture. A chemical library was screened using an in vitro kinase assay to identify novel small molecule inhibitors and further medicinal chemistry was performed to delineate a novel pharmacophore. We demonstrate that aPKC isoforms are both sufficient and required for VEGF-induced endothelial permeability. Furthermore, these specific, potent, non-competitive, small molecule inhibitors prevented VEGF-induced tight junction internalization and retinal endothelial permeability in response to VEGF in both primary culture and in rodent retina. These data suggest that aPKC inhibition with 2-amino-4-phenyl-thiophene derivatives may be developed to preserve the BRB in retinal diseases such as diabetic retinopathy or uveitis and the blood-brain barrier (BBB) in the presence of brain tumors. PMID:22721706

  8. Intact urothelial barrier function in a mouse model of ketamine-induced voiding dysfunction.

    PubMed

    Rajandram, Retnagowri; Ong, Teng Aik; Razack, Azad H A; MacIver, Bryce; Zeidel, Mark; Yu, Weiqun

    2016-05-01

    Ketamine is a popular choice for young drug abusers. Ketamine abuse causes lower urinary tract symptoms, with the underlying pathophysiology poorly understood. Disruption of urothelial barrier function has been hypothesized to be a major mechanism for ketamine cystitis, yet the direct evidence of impaired urothelial barrier function is still lacking. To address this question, 8-wk-old female C57BL/6J mice were injected intraperitoneally with 30 mg·kg(-1)·day(-1) ketamine for 12 wk to induce ketamine cystitis. A spontaneous voiding spot assay showed that ketamine-treated mice had increased primary voiding spot numbers and smaller primary voiding spot sizes than control mice (P < 0.05), indicating a contracted bladder and bladder overactivity. Consistently, significantly increased voiding frequency was observed in ketamine-treated mice on cystometrograms. These functional experiments indicate that ketamine induces voiding dysfunction in mice. Surprisingly, urothelial permeability in ketamine-treated mice was not changed when measured using an Ussing chamber system with isotopic urea and water. Mouse urothelial structure was also not altered, and intact umbrella cell structure was observed by both transmission and scanning electron microscopy. Furthermore, immunostaining and confocal microscopy confirmed the presence of a well-defined distribution of zonula occuldens-1 in tight junctions and uroplakin in umbrella cells. In conclusion, these data indicate that ketamine injection induces voiding dysfunction in mice but does not necessarily disrupt mouse bladder barrier function. Disruption of urothelial barrier function may not be the major mechanism in ketamine cystitis. PMID:26911853

  9. Lipopolysaccharide-induced pulmonary endothelial barrier disruption and lung edema: critical role for bicarbonate stimulation of AC10.

    PubMed

    Nickols, Jordan; Obiako, Boniface; Ramila, K C; Putinta, Kevin; Schilling, Sarah; Sayner, Sarah L

    2015-12-15

    Bacteria-induced sepsis is a common cause of pulmonary endothelial barrier dysfunction and can progress toward acute respiratory distress syndrome. Elevations in intracellular cAMP tightly regulate pulmonary endothelial barrier integrity; however, cAMP signals are highly compartmentalized: whether cAMP is barrier-protective or -disruptive depends on the compartment (plasma membrane or cytosol, respectively) in which the signal is generated. The mammalian soluble adenylyl cyclase isoform 10 (AC10) is uniquely stimulated by bicarbonate and is expressed in pulmonary microvascular endothelial cells (PMVECs). Elevated extracellular bicarbonate increases cAMP in PMVECs to disrupt the endothelial barrier and increase the filtration coefficient (Kf) in the isolated lung. We tested the hypothesis that sepsis-induced endothelial barrier disruption and increased permeability are dependent on extracellular bicarbonate and activation of AC10. Our findings reveal that LPS-induced endothelial barrier disruption is dependent on extracellular bicarbonate: LPS-induced barrier failure and increased permeability are exacerbated in elevated bicarbonate compared with low extracellular bicarbonate. The AC10 inhibitor KH7 attenuated the bicarbonate-dependent LPS-induced barrier disruption. In the isolated lung, LPS failed to increase Kf in the presence of minimal perfusate bicarbonate. An increase in perfusate bicarbonate to the physiological range (24 mM) revealed the LPS-induced increase in Kf, which was attenuated by KH7. Furthermore, in PMVECs treated with LPS for 6 h, there was a dose-dependent increase in AC10 expression. Thus these findings reveal that LPS-induced pulmonary endothelial barrier failure requires bicarbonate activation of AC10. PMID:26475732

  10. Chronic Kidney Disease Induced Intestinal Mucosal Barrier Damage Associated with Intestinal Oxidative Stress Injury

    PubMed Central

    Yu, Chao; Wang, Qiang; Zhou, Chunyu; Kang, Xin; Zhao, Shuang; Liu, Shuai; Fu, Huijun; Yu, Zhen; Peng, Ai

    2016-01-01

    Background. To investigate whether intestinal mucosal barrier was damaged or not in chronic kidney disease progression and the status of oxidative stress. Methods. Rats were randomized into two groups: a control group and a uremia group. The uremia rat model was induced by 5/6 kidney resection. In postoperative weeks (POW) 4, 6, 8, and 10, eight rats were randomly selected from each group to prepare samples for assessing systemic inflammation, intestinal mucosal barrier changes, and the status of intestinal oxidative stress. Results. The uremia group presented an increase trend over time in the serum tumor necrosis factor-alpha, interleukin-6 (IL-6) and IL-10, serum D-lactate and diamine oxidase, and intestinal permeability, and these biomarkers were significantly higher than those in control group in POW 8 and/or 10. Chiu's scores in uremia group were also increased over time, especially in POW 8 and 10. Furthermore, the intestinal malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were significantly higher in uremia group when compared with those in control group in POW 8 and/or 10. Conclusions. The advanced chronic kidney disease could induce intestinal mucosal barrier damage and further lead to systemic inflammation. The underlying mechanism may be associated with the intestinal oxidative stress injury. PMID:27493661

  11. 1,25-Dihydroxyvitamin D3 prevents toluene diisocyanate-induced airway epithelial barrier disruption.

    PubMed

    Li, Wenjia; Dong, Hangming; Zhao, Haijin; Song, Jiafu; Tang, Haixiong; Yao, Lihong; Liu, Laiyu; Tong, Wancheng; Zou, Mengchen; Zou, Fei; Cai, Shaoxi

    2015-07-01

    The loss of airway epithelial integrity contributes significantly to asthma pathogenesis. Evidence suggests that vitamin D plays an important role in the prevention and treatment of asthma. However, its role in airway epithelial barrier function remains uncertain. We have previously demonstrated impaired epithelial junctions in a model of toluene diisocyanate (TDI)-induced asthma. In the present study, we hypothesized that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may prevent TDI-induced epithelial barrier disruption. Male BALB/c mice were dermally sensitized and then challenged with TDI. The mice were then administered 1,25(OH)2D3 intraperitoneally prior to challenge with TDI. For in vitro experiments, 16HBE bronchial epithelial cells were cultured and stimulated with TDI-human serum albumin (HSA). The results revealed that the mice treated with 1,25(OH)2D3 displayed decreased airway hyperresponsiveness (AHR), suppressed neutrophil and eosinophil infiltration into the airways, as well as an increased E-cadherin and zonula occludens-1 (ZO-1) expression at the cell-cell contact sites. In vitro, exposure of the cells to TDI-HSA induced a rapid decline in transepithelial electrical resistance (TER) and an increase in cell permeability, followed by a decrease in occludin expression and the redistribution of E-cadherin, accompanied by a significant upregulation in the levels of phosphorylated extracellular signal-regulated kinase (ERK)1/2. These effects were all partly reversed by treatment with either 1,25(OH)2D3 or an ERK1/2 inhibitor. In conclusion, the findings of our study demonstrate that 1,25(OH)2D3 prevents TDI-induced epithelial barrier disruption, and that the ERK1/2 pathway may play a role in this process. PMID:25998793

  12. Activation of muscarinic cholinoceptor ameliorates tumor necrosis factor-α-induced barrier dysfunction in intestinal epithelial cells.

    PubMed

    Khan, Md Rafiqul Islam; Uwada, Junsuke; Yazawa, Takashi; Islam, Md Tariqul; Krug, Susanne M; Fromm, Michael; Karaki, Shin-ichiro; Suzuki, Yuichi; Kuwahara, Atsukazu; Yoshiki, Hatsumi; Sada, Kiyonao; Muramatsu, Ikunobu; Anisuzzaman, Abu Syed Md; Taniguchi, Takanobu

    2015-11-30

    Impaired intestinal barrier function is one of the critical issues in inflammatory bowel diseases. The aim of this study is to investigate muscarinic cholinoceptor (mAChR)-mediated signaling for the amelioration of cytokine-induced barrier dysfunction in intestinal epithelium. Rat colon challenged with TNF-α and interferon γ reduced transepithelial electrical resistance (TER). This barrier injury was attenuated by muscarinic stimulation. In HT-29/B6 intestinal epithelial cells, muscarinic stimulation suppressed TNF-α-induced activation of NF-κB signaling and barrier disruption. Finally, muscarinic stimulation promoted the shedding of TNFR1, which would be a mechanism for the attenuation of TNF-α/NF-κB signaling and barrier disruption via mAChR. PMID:26519558

  13. Compact drain-current model for undoped cylindrical surrounding-gate metal-oxide-semiconductor field effect transistors including short channel effects

    NASA Astrophysics Data System (ADS)

    Smaani, Billel; Latreche, Saida; Iñiguez, Benjamín

    2013-12-01

    In this paper, we present a compact model for undoped short-channel cylindrical surrounding-gate MOSFETs. The drain-current model is expressed as a function of the mobile charge density, which is calculated using the analytical expressions of the surface potential and the difference between surface and center potentials model. The short-channel effects are well incorporated in the drain-current model, such as the drain-induced barrier lowering, the charge sharing effect (VT Roll-off), the subthreshold slope degradation, and the channel length modulation. A comparison of the model results with 3D numerical simulations using Silvaco Atlas-TCAD presents a good agreement from subthreshold to strong inversion regime and for different bias voltages.

  14. Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction.

    PubMed

    Kucharekova, M; Schalkwijk, J; Van De Kerkhof, P C M; Van De Valk, P G M

    2002-06-01

    In the present study we compared the effect of a ceramide 3-containing emollient (Locobase(R) Repair) with a control emollient (vaselinum album/cremor lanette ana) and untreated damaged skin using clinical, bioengineering and immunohistochemical methods in two different models of experimentally induced skin barrier dysfunction. In model A (n = 13) skin barrier dysfunction was inflicted at three investigation sites by tape stripping. In model B (n = 13) the volunteers were patch tested at three investigation sites with sodium dodecyl sulphate (0.2%) for 4 h a day for 4 consecutive days. The investigation sites were treated once a day with the above-mentioned agents. Irritant reaction was assessed daily by erythema scoring and measurements of transepidermal water loss (TEWL). After 5D, punch biopsies were taken from all sites. Immunohistochemical assessment was carried out with respect to epidermal proliferation, epidermal differentiation and Langerhans cells. Tape stripping resulted in an erythematous reaction and an increase of TEWL associated with up-regulation of cycling cells, involucrin and expression of cytokeratin 16. At day 4, ceramide 3-containing emollient significantly decreased (p < 0.03) the erythema score, TEWL and cycling cells in comparison with the untreated site. Repetitive exposure to SDS induced a variable degree of erythema, gradual increase of TEWL, an increase of cycling cells, and up-regulation of involucrin, E-FABP and SKALP. The treatment with the control emollient significantly prevented erythema, increase of TEWL and cycling cells at day 4 compared to the untreated site. In summary, the present study demonstrated that both tested emollients improve skin barrier in different conditions compared to the untreated skin. There is some indication that formulations containing skin-related lipids might be of benefit in barrier disruption following tape stripping. Different models and clinical trials are needed to establish the usefulness in

  15. Plumbing the brain drain.

    PubMed Central

    Saravia, Nancy Gore; Miranda, Juan Francisco

    2004-01-01

    Opportunity is the driving force of migration. Unsatisfied demands for higher education and skills, which have been created by the knowledge-based global economy, have generated unprecedented opportunities in knowledge-intensive service industries. These multi-trillion dollar industries include information, communication, finance, business, education and health. The leading industrialized nations are also the focal points of knowledge-intensive service industries and as such constitute centres of research and development activity that proactively draw in talented individuals worldwide through selective immigration policies, employment opportunities and targeted recruitment. Higher education is another major conduit of talent from less-developed countries to the centres of the knowledge-based global economy. Together career and educational opportunities drive "brain drain and recirculation". The departure of a large proportion of the most competent and innovative individuals from developing nations slows the achievement of the critical mass needed to generate the enabling context in which knowledge creation occurs. To favourably modify the asymmetric movement and distribution of global talent, developing countries must implement bold and creative strategies that are backed by national policies to: provide world-class educational opportunities, construct knowledge-based research and development industries, and sustainably finance the required investment for these strategies. Brazil, China and India have moved in this direction, offering world-class education in areas crucial to national development, such as biotechnology and information technology, paralleled by investments in research and development. As a result, only a small proportion of the most highly educated individuals migrate from these countries, and research and development opportunities employ national talent and even attract immigrants. PMID:15375451

  16. Plumbing the brain drain.

    PubMed

    Saravia, Nancy Gore; Miranda, Juan Francisco

    2004-08-01

    Opportunity is the driving force of migration. Unsatisfied demands for higher education and skills, which have been created by the knowledge-based global economy, have generated unprecedented opportunities in knowledge-intensive service industries. These multi-trillion dollar industries include information, communication, finance, business, education and health. The leading industrialized nations are also the focal points of knowledge-intensive service industries and as such constitute centres of research and development activity that proactively draw in talented individuals worldwide through selective immigration policies, employment opportunities and targeted recruitment. Higher education is another major conduit of talent from less-developed countries to the centres of the knowledge-based global economy. Together career and educational opportunities drive "brain drain and recirculation". The departure of a large proportion of the most competent and innovative individuals from developing nations slows the achievement of the critical mass needed to generate the enabling context in which knowledge creation occurs. To favourably modify the asymmetric movement and distribution of global talent, developing countries must implement bold and creative strategies that are backed by national policies to: provide world-class educational opportunities, construct knowledge-based research and development industries, and sustainably finance the required investment for these strategies. Brazil, China and India have moved in this direction, offering world-class education in areas crucial to national development, such as biotechnology and information technology, paralleled by investments in research and development. As a result, only a small proportion of the most highly educated individuals migrate from these countries, and research and development opportunities employ national talent and even attract immigrants. PMID:15375451

  17. Intermedin Stabilized Endothelial Barrier Function and Attenuated Ventilator-induced Lung Injury in Mice

    PubMed Central

    Müller-Redetzky, Holger Christian; Kummer, Wolfgang; Pfeil, Uwe; Hellwig, Katharina; Will, Daniel; Paddenberg, Renate; Tabeling, Christoph; Hippenstiel, Stefan; Suttorp, Norbert; Witzenrath, Martin

    2012-01-01

    Background Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. Methodology/Principal Findings Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1–3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. Conclusions/Significance IMD may possibly provide a new approach to attenuate VILI. PMID:22563471

  18. Interactions between surface discharges induced by volume discharges in a dielectric barrier discharge system

    SciTech Connect

    Gao, Yenan; Dong, Lifang Zhao, Longhu; Wang, Yongjie; Pan, Yuyang; Li, Ben

    2014-10-15

    The interaction between micro-discharges involved in surface discharges (SDs) is studied in dielectric barrier discharge system. Instantaneous images taken by high speed cameras show that the SDs are induced by volume discharges (VDs). They cannot cross the midperpendicular of two neighbouring volume charges at low voltage while they stretch along it at high voltage, indicating that there is interaction between SDs. The differences of plasma parameters between SD and VD are studied by optical emission spectroscopy. The simulation of the electric fields of the wall charges accumulated by VD further confirms the existence of the interaction.

  19. Neuromodulation accompanying focused ultrasound-induced blood-brain barrier opening

    PubMed Central

    Chu, Po-Chun; Liu, Hao-Li; Lai, Hsin-Yi; Lin, Chung-Yin; Tsai, Hong-Chieh; Pei, Yu-Cheng

    2015-01-01

    Burst-mode focused ultrasound (FUS) induces microbubble cavitation in the vasculature and temporarily disrupts the blood-brain barrier (BBB) to enable therapeutic agent delivery. However, it remains unclear whether FUS-induced BBB opening is accompanied by neuromodulation. Here we characterized the functional effects of FUS-induced BBB opening by measuring changes in somatosensory evoked potentials (SSEPs) and blood-oxygen-level dependent (BOLD) responses. Rats underwent burst-mode FUS (mechanical index (MI) of 0.3, 0.55 or 0.8) to the forelimb region in the left primary somatosensory cortex to induce BBB opening. Longitudinal measurements were followed for up to 1 week to characterize the temporal dynamics of neuromodulation. We observed that 0.8-MI FUS profoundly suppressed SSEP amplitude and prolonged latency, and this effect lasted 7 days. 0.55-MI FUS resulted in minimal and short-term suppression of SSEP for less than 60 minutes and didn’t affect latency. BOLD responses were also suppressed in an MI-dependent manner, mirroring the effect on SSEPs. Furthermore, repetitive delivery of 0.55-MI FUS every 3 days elicited no accumulative effects on SSEPs or tissue integrity. This is the first evidence that FUS-induced BBB opening is accompanied by reversible changes in neuron responses, and may provide valuable insight toward the development of FUS-induced BBB opening for clinical applications. PMID:26490653

  20. Relaxation times and energy barriers of rubbing-induced birefringence in glass-forming polymers

    NASA Astrophysics Data System (ADS)

    Shiu, K. P.; Qin, Zongyi; Yang, Z.

    2008-12-01

    The relaxations of rubbing-induced birefringence (RIB) in several glass-forming polymers, including polycarbonate and polystyrene (PS) derivatives with various modifications to the phenyl ring side group, are studied. Significant relaxations of RIB are observed at temperatures well below the glass transition temperature T g . The relaxation times span a wide range from ˜ 10 s to probably geological time scale. Physical aging effects are absent in the RIB relaxations. The model proposed for the interpretation of RIB in PS describes well the RIB relaxations in all the polymers investigated here. The energy barriers are of the order of a few hundred kJ/mol and decrease with decreasing temperature, in opposition to the trend of Vogel-Fulcher form for polymer segmental relaxations above T g . The relaxation behaviors of different polymers are qualitatively similar but somewhat different in quantitative details, such as in the values of the saturated birefringence, the shape of the initial barrier density distribution functions, the rates of barrier decrease with decreasing temperature, and the dependence of relaxation times on temperature and parameter ξ , etc. The RIB relaxations are different from any of the other relaxations below T g that have been reported in the literature, such as dielectric relaxations or optical probe relaxations. A microscopic model for the relaxations of RIB is much desired.

  1. Pitch glide effect induced by a nonlinear string-barrier interaction

    NASA Astrophysics Data System (ADS)

    Kartofelev, Dmitri; Stulov, Anatoli; Välimäki, Vesa

    2015-10-01

    Interactions of a vibrating string with its supports and other spatially distributed barriers play a significant role in the physics of many stringed musical instruments. It is well known that the tone of the string vibrations is determined by the string supports, and that the boundary conditions of the string termination may cause a short-lasting initial fundamental frequency shifting. Generally, this phenomenon is associated with the nonlinear modulation of the stiff string tension. The aim of this paper is to study the initial frequency glide phenomenon that is induced only by the string-barrier interaction, apart from other possible physical causes, and without the interfering effects of dissipation and dispersion. From a numerical simulation perspective, this highly nonlinear problem may present various difficulties, not the least of which is the risk of numerical instability. We propose a numerically stable and a purely kinematic model of the string-barrier interaction, which is based on the travelling wave solution of the ideal string vibration. The model is capable of reproducing the motion of the vibrating string exhibiting the initial fundamental frequency glide, which is caused solely by the complex nonlinear interaction of the string with its termination. The results presented in this paper can expand our knowledge and understanding of the timbre evolution and the physical principles of sound generation of numerous stringed instruments, such as lutes called the tambura, sitar and biwa.

  2. Under-the-barrier dynamics in laser-induced relativistic tunneling.

    PubMed

    Klaiber, Michael; Yakaboylu, Enderalp; Bauke, Heiko; Hatsagortsyan, Karen Z; Keitel, Christoph H

    2013-04-12

    The tunneling dynamics in relativistic strong-field ionization is investigated with the aim to develop an intuitive picture for the relativistic tunneling regime. We demonstrate that the tunneling picture applies also in the relativistic regime by introducing position dependent energy levels. The quantum dynamics in the classically forbidden region features two time scales, the typical time that characterizes the probability density's decay of the ionizing electron under the barrier (Keldysh time) and the time interval which the electron spends inside the barrier (Eisenbud-Wigner-Smith tunneling time). In the relativistic regime, an electron momentum shift as well as a spatial shift along the laser propagation direction arise during the under-the-barrier motion which are caused by the laser magnetic field induced Lorentz force. The momentum shift is proportional to the Keldysh time, while the wave-packet's spatial drift is proportional to the Eisenbud-Wigner-Smith time. The signature of the momentum shift is shown to be present in the ionization spectrum at the detector and, therefore, observable experimentally. In contrast, the signature of the Eisenbud-Wigner-Smith time delay disappears at far distances for pure quasistatic tunneling dynamics. PMID:25167261

  3. Hypoxia-Inducible Factor 1–Dependent Induction of Intestinal Trefoil Factor Protects Barrier Function during Hypoxia

    PubMed Central

    Furuta, Glenn T.; Turner, Jerrold R.; Taylor, Cormac T.; Hershberg, Robert M.; Comerford, Katrina; Narravula, Sailaja; Podolsky, Daniel K.; Colgan, Sean P.

    2001-01-01

    Mucosal organs such as the intestine are supported by a rich and complex underlying vasculature. For this reason, the intestine, and particularly barrier-protective epithelial cells, are susceptible to damage related to diminished blood flow and concomitant tissue hypoxia. We sought to identify compensatory mechanisms that protect epithelial barrier during episodes of intestinal hypoxia. Initial studies examining T84 colonic epithelial cells revealed that barrier function is uniquely resistant to changes elicited by hypoxia. A search for intestinal-specific, barrier-protective factors revealed that the human intestinal trefoil factor (ITF) gene promoter bears a previously unappreciated binding site for hypoxia-inducible factor (HIF)-1. Hypoxia resulted in parallel induction of ITF mRNA and protein. Electrophoretic mobility shift assay analysis using ITF-specific, HIF-1 consensus motifs resulted in a hypoxia-inducible DNA binding activity, and loading cells with antisense oligonucleotides directed against the α chain of HIF-1 resulted in a loss of ITF hypoxia inducibility. Moreover, addition of anti-ITF antibody resulted in a loss of barrier function in epithelial cells exposed to hypoxia, and the addition of recombinant human ITF to vascular endothelial cells partially protected endothelial cells from hypoxia-elicited barrier disruption. Extensions of these studies in vivo revealed prominent hypoxia-elicited increases in intestinal permeability in ITF null mice. HIF-1–dependent induction of ITF may provide an adaptive link for maintenance of barrier function during hypoxia. PMID:11342587

  4. THE ROLE OF MIR-212 AND INOS IN ALCOHOL-INDUCED INTESTINAL BARRIER DYSFUNCTION AND STEATOHEPATITIS

    PubMed Central

    Tang, Yueming; Zhang, Lijuan; Forsyth, Christopher B.; Shaikh, Maliha; Song, Shiwen; Keshavarzian, Ali

    2015-01-01

    Background Alcoholic liver disease (ALD) is commonly associated with intestinal barrier dysfunction. Alcohol-induced dysregulation of intestinal tight junction (TJ) proteins, such as Zonula Occludens-1 (ZO-1), plays an important role in alcohol-induced gut leakiness. However, the mechanism of alcohol-induced disruption of TJ proteins is not well established. The goal of this study was to elucidate this mechanism by studying the role of MicroRNA 212 (miR-212) and inducible nitric oxide synthase (iNOS) in alcohol-induced gut leakiness. Methods The permeability of the Caco-2 monolayer was assessed by transepithelial electrical resistance (TER) and flux of fluorescein sulfonic acid (FSA). miR-212 was measured by real time PCR. The wild type, iNOS knockout, and miR-212 knockdown mice were fed with alcohol diet (29% of total calories, 4.5% v/v) for 8 weeks. The LNA-anti-miR-212 was used to inhibit miR-212 expression in mice. The alcohol-induced intestinal permeability, miR-212 expression and liver injuries in mice were measured. Results Our in vitro monolayer and in vivo mice studies showed that: (1) alcohol-induced over-expression of the intestinal miR-212 and intestinal hyperpermeability is prevented by using miR-212 knock-down techniques; and (2). iNOS is upregulated in the intestine by alcohol and that iNOS signaling is required for alcohol-induced miR-212 over-expression, ZO-1 disruption, gut leakiness and steatohepatis. Conclusions These studies thus support a novel miR-212 mechanism for alcohol-induced gut leakiness and a potential target that could be exploited for therapeutic intervention to prevent leaky gut and liver injury in alcoholics. PMID:26207424

  5. Coma due to malplaced external ventricular drain.

    PubMed

    Chai, Feng Yih; Farizal, Fadzil; Jegan, Thanabalan

    2013-01-01

    Ventriculostomy or external ventricular drain (EVD) placement by free-hand technique has a high malplacement rate. It is a blind procedure that often requires multiple attempts and revisions. To date, no neurological complication due to EVD malplacement has been reported in the literature. In this report, we present the first case of coma induced by a malplaced EVD and the patient regained consciousness after the drain was adjusted. Our discussion focused on various techniques that can improve the accuracy of EVD insertion. EVD insertion under image guidance provides better accuracy with limited disadvantages. We hypothesized that the patient's coma was due to the mass effect and irritation of the malplaced EVD exerted onto the ventral periaqueductal grey matter and the ascending neurons from upper brainstem. PMID:24101284

  6. Closed suction drain with bulb

    MedlinePlus

    ... gloves Five or 6 cotton swabs Gauze pads Clean soapy water Plastic trash bag Surgical tape Waterproof pad or ... Use a cotton swab dipped in the soapy water to clean the skin around the drain. Do this 3 ...

  7. Cross sections and barriers for nuclear fission induced by high-energy nucleons

    SciTech Connect

    Grudzevich, O. T.; Yavshits, S. G.

    2013-03-15

    The cross sections for the fission of {sup 232}Th, {sup 235,238}U, {sup 237}Np, and {sup 239}Pu target nuclei that was induced by 20- to 1000-MeV neutrons and protons were calculated. The respective calculations were based on the multiconfiguration-fission (MCFx) model, which was used to describe three basic stages of the interaction of high-energy nucleons with nuclei: direct processes (intranuclear cascade), equilibration of the emerging compound system, and the decay of the compound nucleus (statistical model). Fission barriers were calculated within the microscopic approach for isotopic chains formed by 15 to 20 nuclei of the required elements. The calculated fission cross sections were compared with available experimental data. It was shown that the input data set and the theoretical model used made it possible to predict satisfactorily cross section for nuclear fission induced by 20- to 1000-MeV nucleons.

  8. Molecular targets in radiation-induced blood-brain barrier disruption

    SciTech Connect

    Nordal, Robert A.; Wong, C. Shun . E-mail: shun.wang@sw.ca

    2005-05-01

    Disruption of the blood-brain barrier (BBB) is a key feature of radiation injury to the central nervous system. Studies suggest that endothelial cell apoptosis, gene expression changes, and alteration of the microenvironment are important in initiation and progression of injury. Although substantial effort has been directed at understanding the impact of radiation on endothelial cells and oligodendrocytes, growing evidence suggests that other cell types, including astrocytes, are important in responses that include induced gene expression and microenvironmental changes. Endothelial apoptosis is important in early BBB disruption. Hypoxia and oxidative stress in the later period that precedes tissue damage might lead to astrocytic responses that impact cell survival and cell interactions. Cell death, gene expression changes, and a toxic microenvironment can be viewed as interacting elements in a model of radiation-induced disruption of the BBB. These processes implicate particular genes and proteins as targets in potential strategies for neuroprotection.

  9. Estrogen protects the blood-brain barrier from inflammation-induced disruption and increased lymphocyte trafficking.

    PubMed

    Maggioli, E; McArthur, S; Mauro, C; Kieswich, J; Kusters, D H M; Reutelingsperger, C P M; Yaqoob, M; Solito, E

    2016-01-01

    Sex differences have been widely reported in neuroinflammatory disorders, focusing on the contributory role of estrogen. The microvascular endothelium of the brain is a critical component of the blood-brain barrier (BBB) and it is recognized as a major interface for communication between the periphery and the brain. As such, the cerebral capillary endothelium represents an important target for the peripheral estrogen neuroprotective functions, leading us to hypothesize that estrogen can limit BBB breakdown following the onset of peripheral inflammation. Comparison of male and female murine responses to peripheral LPS challenge revealed a short-term inflammation-induced deficit in BBB integrity in males that was not apparent in young females, but was notable in older, reproductively senescent females. Importantly, ovariectomy and hence estrogen loss recapitulated an aged phenotype in young females, which was reversible upon estradiol replacement. Using a well-established model of human cerebrovascular endothelial cells we investigated the effects of estradiol upon key barrier features, namely paracellular permeability, transendothelial electrical resistance, tight junction integrity and lymphocyte transmigration under basal and inflammatory conditions, modeled by treatment with TNFα and IFNγ. In all cases estradiol prevented inflammation-induced defects in barrier function, action mediated in large part through up-regulation of the central coordinator of tight junction integrity, annexin A1. The key role of this protein was then further confirmed in studies of human or murine annexin A1 genetic ablation models. Together, our data provide novel mechanisms for the protective effects of estrogen, and enhance our understanding of the beneficial role it plays in neurovascular/neuroimmune disease. PMID:26321046

  10. Bacillus cereus Induces Permeability of the Blood Ocular Barrier During Experimental Endophthalmitis

    PubMed Central

    Moyer, A. L.; Ramadan, R. T.; Novosad, B.; Astley, R.; Callegan, M. C.

    2010-01-01

    Purpose The purpose of this study was to determine to what extent blood retina barrier (BRB) permeability occurred during experimental Bacillus cereus endophthalmitis and whether tight junction alterations were involved in permeability. Methods Mice were intravitreally injected with 100 CFU B. cereus and eyes were analyzed at specific times postinfection for permeability to fibrin and albumin, quantitation of intraocular plasma constituent leakage, production of inflammatory cytokines, and alterations in tight junction protein localization and expression at the level of the RPE. Results B. cereus-induced leakage of albumin and fibrin into the aqueous and vitreous humor by 8 h postinfection. BRB permeability occurred as early as 4 h and increased 13.30-fold compared to uninfected controls by 8 h. Production of proinflammatory cytokines IL-6, MIP-1α, IL-1β, and KC increased over the course of infection. In the retina, ZO-1 disruption begins by 4 h, followed by decreasing occludin and ZO-1 expression at 4 and 8 h, respectively. Tubulin condensation and RPE65 degradation occurred by 12 h. A quorum sensing mutant B. cereus strain caused BRB permeability comparable to that of wild-type B. cereus. Both wild-type and mutant B. cereus sterile supernatants induced blood ocular barrier permeability similarly to that of wild-type infection. Conclusions These results indicate that BRB permeability occurs during the early stages of experimental B. cereus endophthalmitis, beginning as early as 4 h postinfection. Disruption of tight junctions at the level of the RPE may contribute to barrier breakdown. Quorum-sensing dependent factors may not significantly contribute to BRB permeability. PMID:19264886

  11. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats

    PubMed Central

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R.; Tóth, Andrea E.; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A.

    2016-01-01

    Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and

  12. Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress

    PubMed Central

    KIM, KI CHEON; PIAO, MEI JING; HEWAGE, SUSARA RUWAN KUMARA MADDUMA; HAN, XIA; KANG, KYOUNG AH; JO, JIN OH; MOK, YOUNG SUN; SHIN, JENNIFER H.; PARK, YEUNSOO; YOO, SUK JAE; HYUN, JIN WON

    2016-01-01

    The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, the cells were exposed to surface dielectric-barrier discharge plasma in 70% oxygen and 30% argon. We noted that cell viability was decreased following exposure of the cells to plasma in a time-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of intracellular reactive oxygen species (ROS) were determined using 2′,7′-dichlorodihydro-fluorescein diacetate and dihydroethidium was used to monitor superoxide anion production. Plasma induced the generation of ROS, including superoxide anions, hydrogen peroxide and hydroxyl radicals. N-acetyl cysteine, which is an antioxidant, prevented the decrease in cell viability caused by exposure to plasma. ROS generated by exposure to plasma resulted in damage to various cellular components, including lipid membrane peroxidation, DNA breaks and protein carbonylation, which was detected by measuring the levels of 8-isoprostane and diphenyl-1-pyrenylphosphine assay, comet assay and protein carbonyl formation. These results suggest that plasma exerts cytotoxic effects by causing oxidative stress-induced damage to cellular components. PMID:26573561

  13. Non-thermal dielectric-barrier discharge plasma damages human keratinocytes by inducing oxidative stress.

    PubMed

    Kim, Ki Cheon; Piao, Mei Jing; Madduma Hewage, Susara Ruwan Kumara; Han, Xia; Kang, Kyoung Ah; Jo, Jin Oh; Mok, Young Sun; Shin, Jennifer H; Park, Yeunsoo; Yoo, Suk Jae; Hyun, Jin Won

    2016-01-01

    The aim of this study was to identify the mechanisms through which dielectric-barrier discharge plasma damages human keratinocytes (HaCaT cells) through the induction of oxidative stress. For this purpose, the cells were exposed to surface dielectric-barrier discharge plasma in 70% oxygen and 30% argon. We noted that cell viability was decreased following exposure of the cells to plasma in a time-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The levels of intracellular reactive oxygen species (ROS) were determined using 2',7'-dichlorodihydrofluorescein diacetate and dihydroethidium was used to monitor superoxide anion production. Plasma induced the generation of ROS, including superoxide anions, hydrogen peroxide and hydroxyl radicals. N-acetyl cysteine, which is an antioxidant, prevented the decrease in cell viability caused by exposure to plasma. ROS generated by exposure to plasma resulted in damage to various cellular components, including lipid membrane peroxidation, DNA breaks and protein carbonylation, which was detected by measuring the levels of 8-isoprostane and diphenyl-1-pyrenylphosphine assay, comet assay and protein carbonyl formation. These results suggest that plasma exerts cytotoxic effects by causing oxidative stress-induced damage to cellular components. PMID:26573561

  14. Stress Induces Endotoxemia and Low-Grade Inflammation by Increasing Barrier Permeability

    PubMed Central

    de Punder, Karin; Pruimboom, Leo

    2015-01-01

    Chronic non-communicable diseases (NCDs) are the leading causes of work absence, disability, and mortality worldwide. Most of these diseases are associated with low-grade inflammation. Here, we hypothesize that stresses (defined as homeostatic disturbances) can induce low-grade inflammation by increasing the availability of water, sodium, and energy-rich substances to meet the increased metabolic demand induced by the stressor. One way of triggering low-grade inflammation is by increasing intestinal barrier permeability through activation of various components of the stress system. Although beneficial to meet the demands necessary during stress, increased intestinal barrier permeability also raises the possibility of the translocation of bacteria and their toxins across the intestinal lumen into the blood circulation. In combination with modern life-style factors, the increase in bacteria/bacterial toxin translocation arising from a more permeable intestinal wall causes a low-grade inflammatory state. We support this hypothesis with numerous studies finding associations with NCDs and markers of endotoxemia, suggesting that this process plays a pivotal and perhaps even a causal role in the development of low-grade inflammation and its related diseases. PMID:26029209

  15. Blood-ocular and blood-brain barrier function in streptozocin-induced diabetes in rats

    SciTech Connect

    Maeepea, O.; Karlsson, C.; Alm, A.

    1984-09-01

    Edetic acid labeled with chromium 51 was injected intravenously in normal rats and in rats with streptozocin-induced diabetes. One hour after the injection the animals were killed and the concentrations of edetic acid 51Cr in vitreous body, retina, and brain were determined. No significant difference was observed between the two groups for either tissue. In a second series, a mixture of tritiated 1-glucose and aminohippuric acid tagged with carbon 14 was injected instead of edetic acid. A substantial accumulation of aminohippuric acid 14C compared with tritiated 1-glucose was observed in the vitreous body and the brain of diabetic rats in comparison with the control group. It is concluded that untreated streptozocin-induced diabetes in rats for one to two weeks will not cause a generalized increase in the permeability of the blood-ocular or the blood-brain barriers, but organic acids may accumulate in the vitreous body as well as in the brain as a consequence of reduced outward transport through these barriers.

  16. Stress-induced breakdown of intestinal barrier function in the rat: reversal by wood creosote.

    PubMed

    Kuge, Tomoo; Greenwood-Van Meerveld, Beverley; Sokabe, Masahiro

    2006-07-24

    Our previous studies demonstrated that wood creosote (Seirogan) inhibits intestinal secretion and normalizes the transport of electrolytes and water in rats subjected to restraint stress. The goal of the present study was to examine whether wood creosote has a protective effect against stress-induced breakdown of intestinal barrier function. F-344 rats were subjected to 90-min water avoidance stress (WAS) with wood creosote (30 mg/kg) or vehicle administered intragastrically 30 min prior to WAS. Sham stressed rats received wood creosote or vehicle treatment but did not experience the WAS. All rats were euthanized at the end of the WAS or sham-stress and the jejunum and colon were isolated. Epithelial transport was studied in modified Ussing chambers. Spontaneous secretion was assessed by electrophysiological measurement of the short circuit current (I(sc)) while electrical conductance (G) was calculated from the potential difference (PD) and I(sc) using Ohm's law. Intestinal permeability was defined by the mucosal-to-serosal flux of horseradish peroxidase (HRP). WAS significantly elevated basal I(sc) and G and increased epithelial permeability to HRP in the jejunum but not in the colon. Wood creosote resulted in a significant reduction of the stress-induced increase in I(sc), G and the mucosal-to-serosal flux of HRP compared to the vehicle-treated group. Wood creosote caused no significant effects in sham-stressed rats. The results suggest that oral administration of wood creosote may prevent stress-induced diarrhea by preventing aversive effects on small intestinal secretion and barrier function. PMID:16643959

  17. Wave induced barrier transparency and melting of quasi-crystalline structures in two dimensional plasma turbulence

    SciTech Connect

    Das, Amita

    2007-04-15

    The conservation of energy and enstrophy in two dimensional inviscid hydrodynamics leads to dual cascade behavior. The energy cascades towards long scales and the enstrophy is transferred to shorter scales. The interplay of these dynamical processes leads to self organization and formation of coherent patterns in the two dimensional hydrodynamic turbulence. It was shown by Kukharkin et al. [Phys. Rev. Lett. 25, 2486 (1995)] that this process of self organization occurs in an even more interesting fashion in the Hasegawa Mima (HM) equation [Phys. Fluids 21, 21 (1978)] This equation is a generalization of the two dimensional Navier Stokes hydrodynamics model in which there is a characteristic natural scale in the system (e.g., Larmor radius in the drift wave context). Kukharkin et al. observed that this scale acts as a barrier in the energy cascade, such that the cascade rate at the longer wavelength side of the barrier is smaller. This work has also shown that the accumulation of energy around the intrinsic scale leads to the formation of quasi-crystalline patterns. In the present paper it has been demonstrated that the presence of wave excitations leads to an increased cascade towards longer scales past the natural length scale barrier. It has also been demonstrated that wave excitations lead to the melting of quasi-crystalline structures. Another intriguing but interesting observation is that even though the faster cascade is induced by waves arising through an anisotropic inhomogeneity in one of the plasma parameters, the spectrum of the fluctuations continues to remain predominantly isotropic. A physical understanding of the observations is provided by illustrating a close connection between the Kelvin-Helmholtz destabilization of shear flows and the phenomenon of inverse cascade in 2D fluid flows.

  18. Atmospheric pressure resistive barrier air plasma jet induced bacterial inactivation in aqueous environment

    NASA Astrophysics Data System (ADS)

    Thiyagarajan, Magesh; Sarani, Abdollah; Gonzales, Xavier

    2013-03-01

    An atmospheric pressure resistive barrier air plasma jet is designed to inactivate bacteria in aqueous media in direct and indirect exposure modes of treatment. The resistive barrier plasma jet is designed to operate at both dc and standard 50-60 Hz low frequency ac power input and the ambient air at 50% humidity level was used as the operating gas. The voltage-current characteristics of the plasma jet were analyzed and the operating frequency of the discharge was measured to be 20 kHz and the plasma power was measured to be 26 W. The plasma jet rotational temperatures (Trot) are obtained from the optical emission spectra, from the N2C-B(2+) transitions by matching the experimental spectrum results with the Spectra Air (SPECAIR) simulation spectra. The reactive oxygen and nitrogen species were measured using optical emission spectroscopy and gas analyzers, for direct and indirect treatment modes. The nitric oxides (NO) were observed to be the predominant long lived reactive nitrogen species produced by the plasma. Three different bacteria including Staphylococcus aureus (Gram-positive), Escherichia coli (Gram-negative), and Neisseria meningitidis (Gram-negative) were suspended in an aqueous media and treated by the resistive barrier air plasma jet in direct and indirect exposure modes. The results show that a near complete bacterial inactivation was achieved within 120 s for both direct and indirect plasma treatment of S. aureus and E. coli bacteria. Conversely, a partial inactivation of N. meningitidis was observed by 120 s direct plasma exposure and insignificant inactivation was observed for the indirect plasma exposure treatment. Plasma induced shifts in N. meningitidis gene expression was analyzed using pilC gene expression as a representative gene and the results showed a reduction in the expression of the pilC gene compared to untreated samples suggesting that the observed protection against NO may be regulated by other genes.

  19. Early impairment of skeletal muscle endothelial glycocalyx barrier properties in diet‐induced obesity in mice

    PubMed Central

    Eskens, Bart J. M.; Leurgans, Thomas M.; Vink, Hans; VanTeeffelen, Jurgen W. G. E.

    2014-01-01

    Abstract While previous studies have indicated an important role for the endothelial glycocalyx in regulation of microvascular function, it was recently shown that acute enzymatic glycocalyx degradation in rats was associated with an impaired insulin‐mediated glucose disposal. The aim of this study was to determine whether glycocalyx damage in skeletal muscle occurs at an early stage of diet‐induced obesity (DIO). The microcirculation of the hindlimb muscle of anesthetized C57Bl/6 mice, fed chow (CON) or a high‐fat diet (HFD) for 6 and 18 weeks (w), respectively, was visualized with a Sidestream Dark‐Field camera, and glycocalyx barrier properties were derived from the calculated perfused boundary region (PBR). Subsequently, an intraperitoneal glucose tolerance test was performed and the area under the curve (AUC) of blood glucose was calculated. Impairment of glycocalyx barrier properties was already apparent after 6 weeks of HFD and remained after 18 weeks of HFD (PBR [in μm]: 0.81 ± 0.03 in CON_6w vs. 0.97 ± 0.04 in HFD_6w and 1.02 ± 0.07 in HFD_18w [both P < 0.05]). Glucose intolerance appeared to develop more slowly (AUC [in mmol/L × 120 min]: 989 ± 61 in CON_6w vs. 1204 ± 89 in HFD_6w [P = 0.11] and 1468 ± 84 in HFD_18w [P < 0.05]) than the impairment of glycocalyx barrier properties. The data indicate that damage to the endothelial glycocalyx is an early event in DIO. It is suggested that glycocalyx damage may contribute to the development of insulin resistance in obesity. PMID:24744873

  20. Parameterization of fusion barriers for light-projectiles-induced reactions using the proximity approach

    NASA Astrophysics Data System (ADS)

    Gharaei, R.; Sheibani, J.

    2016-05-01

    In this article we propose a pocket formula for fusion barriers calculated by three versions of the proximity formalism, namely AW 95, Bass 80 and Prox. 2010 potentials, for fusion reactions involving the collisions of the proton and helium projectiles with different targets in mass ranges 51≤ AT ≤ 130 and 40≤ AT ≤ 233 , respectively. For the first type of the colliding systems, it is shown that the proposed pocket formulas are able to predict the actual values of RB and VB within accuracies of ±0.4% and ±0.45% , respectively. Moreover, for the second type of the selected reactions, these accuracies are obtained ±0.24% and ±0.36% , respectively. In this study, the ability of the present pocket formulas is also demonstrated to predict the exact values of the fusion cross sections for our selected mass ranges. A comparison with the results of the previous pocket formulas reveals that our parameterized forms are more successful to reproduce the empirical data of the barrier height and position in the proton- and helium-induced reactions.

  1. Genetic and anatomical basis of the barrier separating wakefulness and anesthetic-induced unresponsiveness.

    PubMed

    Joiner, William J; Friedman, Eliot B; Hung, Hsiao-Tung; Koh, Kyunghee; Sowcik, Mallory; Sehgal, Amita; Kelz, Max B

    2013-01-01

    A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states. PMID:24039590

  2. Genetic and Anatomical Basis of the Barrier Separating Wakefulness and Anesthetic-Induced Unresponsiveness

    PubMed Central

    Hung, Hsiao-Tung; Koh, Kyunghee; Sowcik, Mallory; Sehgal, Amita; Kelz, Max B.

    2013-01-01

    A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states. PMID:24039590

  3. Hot-carrier-induced linear drain current and threshold voltage degradation for thin layer silicon-on-insulator field P-channel lateral double-diffused metal-oxide-semiconductor

    SciTech Connect

    Zhou, Xin; Qiao, Ming; He, Yitao; Li, Zhaoji; Zhang, Bo

    2015-11-16

    Hot-carrier-induced linear drain current (I{sub dlin}) and threshold voltage (V{sub th}) degradations for the thin layer SOI field p-channel lateral double-diffused MOS (pLDMOS) are investigated. Two competition degradation mechanisms are revealed and the hot-carrier conductance modulation model is proposed. In the channel, hot-hole injection induced positive oxide trapped charge and interface trap gives rise to the V{sub th} increasing and the channel conductance (G{sub ch}) decreasing, then reduces I{sub dlin}. In the p-drift region, hot-electron injection induced negative oxide trapped charge enhances the conductance of drift doping resistance (G{sub d}), and then increases I{sub dlin}. Consequently, the eventual I{sub dlin} degradation is controlled by the competition of the two mechanisms due to conductance modulation in the both regions. Based on the model, it is explained that the measured I{sub dlin} anomalously increases while the V{sub th} is increasing with power law. The thin layer field pLDMOS exhibits more severe V{sub th} instability compared with thick SOI layer structure; as a result, it should be seriously evaluated in actual application in switching circuit.

  4. Suppression of current collapse by hole injection from drain in a normally-off GaN-based hybrid-drain-embedded gate injection transistor

    NASA Astrophysics Data System (ADS)

    Tanaka, Kenichiro; Morita, Tatsuo; Umeda, Hidekazu; Kaneko, Saichiro; Kuroda, Masayuki; Ikoshi, Ayanori; Yamagiwa, Hiroto; Okita, Hideyuki; Hikita, Masahiro; Yanagihara, Manabu; Uemoto, Yasuhiro; Takahashi, Satoru; Ueno, Hiroaki; Ishida, Hidetoshi; Ishida, Masahiro; Ueda, Tetsuzo

    2015-10-01

    Current collapse is suppressed up to 800 V of drain voltage in our proposed device, Hybrid-Drain-embedded Gate Injection Transistor (HD-GIT), where an additional p-GaN layer is grown on the AlGaN barrier layer and is connected to the drain electrode. We present, based on a device simulation and electroluminescence study, that the hole injection from the additional drain-side p-GaN at the OFF state compensates the hole emission in the epilayer. As a result, the gate-drain access region is not negatively charged at the OFF state, resulting in the drastic suppression of current collapse in HD-GIT.

  5. Structure Effects in Collisions Induced by Halo and Weakly Bound Nuclei around the Coulomb Barrier

    NASA Astrophysics Data System (ADS)

    Scuderi, V.; di Pietro, A.; Acosta, L.; Amorini, F.; Borge, M. J. G.; Figuera, P.; Fisichella, M.; Fraile, L. M.; Gomez-Camacho, J.; Jeppesen, H.; Lattuada, M.; Martel, I.; Milin, M.; Musumarra, A.; Papa, M.; Pellegriti, M. G.; Raabe, R.; Randisi, G.; Rizzo, F.; Santonocito, D.; Sanchez, E. M. R.; Scalia, G.; Tengblad, O.; Torresi, D.; Vidal, A. M.; Zadro, M.

    In this contribution, results concerning different reaction channels for the collisions induced by the three Be isotopes, 9,10,11Be, on a 64Zn target at energies around the Coulomb barrier will be presented. The experiments with the radioactive 10,11Be beams were performed at REX-ISOLDE (CERN) whereas the experiment with the stable weakly bound 9Be beam was performed at LNS Catania. Elastic scattering angular distributions have been measured for the three systems 9,10,11Be + 64Zn at the same center of mass energy. The angular distributions were analyzed with optical potentials and reaction cross sections were obtained from optical model calculations, performed with the code PTOLEMY. For the 11Be + 64Zn reaction, the break-up angular distribution was also measured.

  6. Wire-to-Plate Surface Dielectric Barrier Discharge and Induced Ionic Wind

    NASA Astrophysics Data System (ADS)

    Zhang, Yu; Liu, Lijuan; Li, Ben; Ouyang, Jiting

    2016-06-01

    The electrical and mechanical characteristics of the wire-to-plate surface dielectric barrier discharge and the induced ionic wind are investigated experimentally. The different temporal behaviors in positive and negative half-cycles are studied by time-resolved images. It is shown that the discharge and the light emission are generally stronger in the positive half cycle. The discharge is inhomogeneous and propagates in streamer mode; however, in the negative half-cycle, the discharge appears visually uniformly and operates in the diffuse mode. The surface discharge can produce ionic wind about several m/s above the dielectric surface. There exists an optimal width of the grounded electrode to produce a larger plasma area or active wind region. Increasing of the applied voltage or normalized dielectric constant leads to a larger wind velocity. The performance of ionic wind on flow control is visualized by employing a smoke stream. supported by National Natural Science Foundation of China (Nos. 11175017 and 11475019)

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

    PubMed

    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. PMID:25859243

  8. Effect of arctiin on glomerular filtration barrier damage in STZ-induced diabetic nephropathy rats.

    PubMed

    Ma, Song-Tao; Liu, Dong-lian; Deng, Jing-jing; Niu, Rui; Liu, Rui-bin

    2013-10-01

    Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin content were measured, and kidney histopathological changes were monitored. RT-PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24-h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up-regulating the expression of nephrin and podocin and down-regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ-induced diabetic rats. PMID:23147865

  9. Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood–brain barrier integrity

    PubMed Central

    Zougbédé, Sergine; Miller, Florence; Ravassard, Philippe; Rebollo, Angelita; Cicéron, Liliane; Couraud, Pierre-Olivier; Mazier, Dominique; Moreno, Alicia

    2011-01-01

    The pathogenesis of cerebral malaria (CM) remains largely unknown. There is growing evidence that combination of both parasite and host factors could be involved in blood–brain barrier (BBB) breakdown. However, lack of adequate in vitro model of human BBB so far hampered molecular studies. In this article, we propose the use of hCMEC/D3 cells, a well-established human cerebral microvascular endothelial cell (EC) line, to study BBB breakdown induced by Plasmodium falciparum-parasitized red blood cells and environmental conditions. We show that coculture of parasitized erythrocytes with hCMEC/D3 cells induces cell adhesion and paracellular permeability increase, which correlates with disorganization of zonula occludens protein 1 expression pattern. Permeability increase and modification of tight junction proteins distribution are cytoadhesion independent. Finally, we show that permeability of hCMEC/D3 cell monolayers is mediated through parasite induced metabolic acidosis, which in turns correlates with apoptosis of parasitized erythrocytes. This new coculture model represents a very useful tool, which will improve the knowledge of BBB breakdown and the development of adjuvant therapies, together with antiparasitic drugs. PMID:20683453

  10. Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction

    PubMed Central

    Czikora, Istvan; Sridhar, Supriya; Gorshkov, Boris; Alieva, Irina B.; Kasa, Anita; Gonzales, Joyce; Potapenko, Olena; Umapathy, Nagavedi S.; Pillich, Helena; Rick, Ferenc G.; Block, Norman L.; Verin, Alexander D.; Chakraborty, Trinad; Matthay, Michael A.; Schally, Andrew V.; Lucas, Rudolf

    2014-01-01

    Rationale: Antibiotic treatment of patients infected with G− or G+ bacteria promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV-1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor (GHRH-R) signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated protein kinase A (PKA) depletion. Methods: Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS) and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye (EBD) incorporation. Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by multiplex analysis. PKA and PKC-α activity were assessed by Western blotting. Results: GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-α activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. Conclusions: GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-α-induced pathway in the presence of PLY, the

  11. Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model

    PubMed Central

    Weixia, Du; Hong, Wei

    2016-01-01

    Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ). Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC). It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P < 0.01). Compared with the LPS group, bifidobacterium significantly decreased the production of IL-6 and TNF-α (P < 0.01) and suppressed zonulin release (P < 0.05). In addition, bifidobacterium pretreatment up-regulated occludin, claudin-3 and ZO-1 expression (P < 0.01) and also preserved these proteins localization at TJ compared with the LPS group. In the in vivo study, bifidobacterium decreased the incidence of NEC from 88 to 47% (P < 0.05) and reduced the severity in the NEC model. Increased levels of IL-6 and TNF-α in the ileum of NEC rats were normalized in bifidobacterium treated rats (P < 0.05). Moreover, administration of bifidobacterium attenuated the increase in intestinal permeability (P < 0.01), decreased the levels of serum zonulin (P < 0.05), normalized the expression and localization of TJ proteins in the ileum compared with animals with NEC. We concluded that bifidobacterium may protect against

  12. TIMAP protects endothelial barrier from LPS-induced vascular leakage and is down-regulated by LPS

    PubMed Central

    Poirier, Christophe; Gorshkov, Boris A.; Zemskova, Marina A.; Bogatcheva, Natalia V.; Verin, Alexander D.

    2011-01-01

    TIMAP is a regulatory subunit of protein phosphatase 1, whose role remains largely unknown. Our recent data suggested that TIMAP is involved in the regulation of barrier function in cultured pulmonary endothelial monolayers (Csortos et al., Am J Physiol Lung Cell Mol Physiol 295: L440-450, 2008). Here we showed that TIMAP depletion exacerbates lipopolysaccharide (LPS)-induced vascular leakage in murine lung, suggesting that TIMAP has a barrier-protective role in vivo. Real-Time RT PCR analysis revealed that treatment with LPS significantly suppressed Timap mRNA level. This suppression was not achieved via the down-regulation of Timap promoter activity, suggesting that LPS decreased Timap mRNA stability. Pretreatment with protein kinase A (PKA) inhibitor H-89 reduced TIMAP mRNA level, whereas pretreatment with PKA activator, bnz-cAMP, increased this level and attenuated LPS-induced decrease in TIMAP mRNA. Altogether, these data confirmed the barrier-protective role of TIMAP and suggested that barrier-disruptive and barrier-protective agents may employ modulation of TIMAP expression as a mechanism affecting barrier permeability. PMID:21907835

  13. The effect of damaged skin barrier induced by subclinical irritation on the sequential irritant contact dermatitis.

    PubMed

    Yan-yu, Wu; Xue-min, Wang; Yi-Mei, Tan; Ying, Cheng; Na, Liu

    2011-12-01

    Skin damage caused by a single specific stimulus has been extensively studied. However, many additional mild skin irritants are experienced every day before obvious irritant contact dermatitis (ICD) appears. The effect that these previously experienced mild irritations have on the incidence and severity of sequential ICD remains undefined. The purpose of this work was to explore whether the effects of skin barrier damage induced by either the open patch test with 1% sodium lauryl sulfate (SLS), tape stripping test (TAP) (10×), or irradiation with 0.75 median erythemal dose UVB (MED) will affect the severity of sequential irritant dermatitis induced by a 0.5% SLS occlusive patch test (PT). Nine treatments were applied to nine different locations of the ventral forearm of each subject at random. The nine treatment types were as follows: open patch test with 1% SLS; 10× TAP; UVB irradiation with 0.75 MED; open patch test with 1% SLS + PT with 0.5% SLS (SLSPT); 10× TAP + PT with 0.5% SLS (TAPPT); UVB irradiation with 0.75 MED + PT with 0.5% SLS (UVPT); PT with distilled water (DISPT); PT with 0.5% SLS (PT); and the CONTROL (no treatment). After 5 days of subclinical irritation, the PT was applied on day 6. Transepidermal water loss (TEWL), capacitance (CAP), and skin color (a*) were measured at baseline and on days 6, 7, and 8. After the PT, indices of irritancy of PT, UVPT, SLSPT, and TAPPT were 60, 80, 87 and 100%, respectively. The index of irritancy of TAPPT and SLSPT were significantly higher than that of PT (p < 0.05). Clinical scores of SLSPT and TAPPT were also significantly higher than PT (p < 0.05). After 5 days of irritation, TEWL of SLS, TAP, SLSPT, and TAPPT were increased significantly compared to that of baseline. After the PT, D-value of TEWL between day 8 and day 6 ((≥6-8)TEWL) of SLSPT and TAPPT were greater than that of PT, and D-value of TEWL between day 8 and day 7 ((≥7-8)TEWL) of SLSPT and TAPPT were less than that of PT values. After the

  14. Antioxidant protects blood-testis barrier against synchrotron radiation X-ray-induced disruption

    PubMed Central

    Zhang, Tingting; Liu, Tengyuan; Shao, Jiaxiang; Sheng, Caibin; Hong, Yunyi; Ying, Weihai; Xia, Weiliang

    2015-01-01

    Synchrotron radiation (SR) X-ray has wide biomedical applications including high resolution imaging and brain tumor therapy due to its special properties of high coherence, monochromaticity and high intensity. However, its interaction with biological tissues remains poorly understood. In this study, we used the rat testis as a model to investigate how SR X-ray would induce tissue responses, especially the blood-testis barrier (BTB) because BTB dynamics are critical for spermatogenesis. We irradiated the male gonad with increasing doses of SR X-ray and obtained the testicles 1, 10 and 20 d after the exposures. The testicle weight and seminiferous tubule diameter reduced in a dose- and time-dependent manner. Cryosections of testes were stained with tight junction (TJ) component proteins such as occludin, claudin-11, JAM-A and ZO-1. Morphologically, increasing doses of SR X-ray consistently induced developing germ cell sloughing from the seminiferous tubules, accompanied by shrinkage of the tubules. Interestingly, TJ constituent proteins appeared to be induced by the increasing doses of SR X-ray. Up to 20 d after SR X-ray irradiation, there also appeared to be time-dependent changes on the steady-state level of these protein exhibiting differential patterns at 20-day after exposure, with JAM-A/claudin-11 still being up-regulated whereas occludin/ZO-1 being down-regulated. More importantly, the BTB damage induced by 40 Gy of SR X-ray could be significantly attenuated by antioxidant N-Acetyl-L-Cysteine (NAC) at a dose of 125 mg/kg. Taken together, our studies characterized the changes of TJ component proteins after SR X-ray irradiation, illustrating the possible protective effects of antioxidant NAC to BTB integrity. PMID:26413412

  15. Sieving characteristics of cytokine- and peroxide-induced epithelial barrier leak: Inhibition by berberine

    PubMed Central

    DiGuilio, Katherine M; Mercogliano, Christina M; Born, Jillian; Ferraro, Brendan; To, Julie; Mixson, Brittany; Smith, Allison; Valenzano, Mary Carmen; Mullin, James M

    2016-01-01

    AIM: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak. METHODS: We examined the effects of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1-β (IL1β) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of CACO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of 14C-D-mannitol, 3H-Lactulose and 14C-Polyethylene glycol as radiolabeled probe molecules. The isoquinoline alkaloid, berberine, was then examined for its ability to reduce specific types of transepithelial leak. RESULTS: Exposure to TNF-α alone (200 ng/mL; 48 h) induced a 50% decrease in TER, i.e., increased leak of Na+ and Cl- - with only a marginal but statistically significant increase in transepithelial leak of 14C-mannitol (Jm). Exposure to TNF-α + IFN-γ (200 ng/mL; 48 h) + IL1β (50 ng/mL; 48 h) did not increase the TER change (from TNF-α alone), but there was now a 100% increase in Jm. There however was no increase in transepithelial leak of two larger probe molecules, 3H-lactulose and 14C-polyethylene glycol (PEG). However, exposure to TNF-α + IFN-γ + IL1β followed by a 5 h exposure to 2 mmol/L H2O2 resulted in a 500% increase in 14C-PEG leak as well as leak to the luminal mitogen, epidermal growth factor. CONCLUSION: This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances. PMID:27190695

  16. Salmonella enterica induces joint inflammation and expression of interleukin-17 in draining lymph nodes early after onset of enterocolitis in mice.

    PubMed

    Noto Llana, Mariángeles; Sarnacki, Sebastián Hernán; Vázquez, María Victoria; Gartner, Alejandra Sonia; Giacomodonato, Mónica Nancy; Cerquetti, María Cristina

    2012-06-01

    In developing countries, one-third of reactive arthritis (ReA) cases are associated with Salmonella enterocolitis; nevertheless, there is no animal model for studying this pathology. Here we induced a self-limiting Salmonella enterica serovar Enteritidis enterocolitis in mice to analyze the onset of ReA. BALB/c mice received orally 20 μg of streptomycin 24 h before intragastric inoculation of a low dose (3 × 10(3) to 4 × 10(3) CFU) of S. Enteritidis. In response to Salmonella infection, a 30-fold increase in the expression of interleukin-17 (IL-17), measured by quantitative PCR, was observed in mesenteric lymph nodes 5 days postinfection. At this time synovitis was already evident, and concomitantly, a significant increase in joint tumor necrosis factor alpha (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). The early development of joint lesions was accompanied by an increased expression of IL-17 in inguinal and popliteal lymph nodes. Infection with 10(7) CFU of an isogenic ΔinvG mutant bearing a defective type III secretion system of Salmonella encoded in the pathogenicity island 1 apparatus (TTSS-1) induced enterocolitis histologically similar to that triggered by the wild-type strain. Interestingly, despite the higher infective dose used, the mutant did not trigger intestinal IL-17. Moreover, no synovitis was observed in mice suffering ΔinvG enterocolitis. Neutralization of IL-17 in mice infected with S. Enteritidis prevented both synovitis and the increment of TNF-α in the joints, suggesting that IL-17 participates in the generation of Salmonella-induced ReA through the induction of TNF-α in the joints. PMID:22493084

  17. Bifidobacteria Prevent Tunicamycin-Induced Endoplasmic Reticulum Stress and Subsequent Barrier Disruption in Human Intestinal Epithelial Caco-2 Monolayers.

    PubMed

    Akiyama, Takuya; Oishi, Kenji; Wullaert, Andy

    2016-01-01

    Endoplasmic reticulum (ER) stress is caused by accumulation of unfolded and misfolded proteins in the ER, thereby compromising its vital cellular functions in protein production and secretion. Genome wide association studies in humans as well as experimental animal models linked ER stress in intestinal epithelial cells (IECs) with intestinal disorders including inflammatory bowel diseases. However, the mechanisms linking the outcomes of ER stress in IECs to intestinal disease have not been clarified. In this study, we investigated the impact of ER stress on intestinal epithelial barrier function using human colon carcinoma-derived Caco-2 monolayers. Tunicamycin-induced ER stress decreased the trans-epithelial electrical resistance of Caco-2 monolayers, concomitant with loss of cellular plasma membrane integrity. Epithelial barrier disruption in Caco-2 cells after ER stress was not caused by caspase- or RIPK1-dependent cell death but was accompanied by lysosomal rupture and up-regulation of the ER stress markers Grp78, sXBP1 and Chop. Interestingly, several bifidobacteria species inhibited tunicamycin-induced ER stress and thereby diminished barrier disruption in Caco-2 monolayers. Together, these results showed that ER stress compromises the epithelial barrier function of Caco-2 monolayers and demonstrate beneficial impacts of bifidobacteria on ER stress in IECs. Our results identify epithelial barrier loss as a potential link between ER stress and intestinal disease development, and suggest that bifidobacteria could exert beneficial effects on this phenomenon. PMID:27611782

  18. Nitric oxide attenuates hydrogen peroxide-induced barrier disruption and protein tyrosine phosphorylation in monolayers of intestinal epithelial cell.

    PubMed

    Katsube, Takanori; Tsuji, Hideo; Onoda, Makoto

    2007-06-01

    The intestinal epithelium provides a barrier to the transport of harmful luminal molecules into the systemic circulation. A dysfunctional epithelial barrier is closely associated with the pathogenesis of a variety of intestinal and systemic disorders. We investigated here the effects of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) on the barrier function of a human intestinal epithelial cell line, Caco-2. When treated with H(2)O(2), Caco-2 cell monolayers grown on permeable supports exhibited several remarkable features of barrier dysfunction as follows: a decrease in transepithelial electrical resistance, an increase in paracellular permeability to dextran, and a disruption of the intercellular junctional localization of the scaffolding protein ZO-1. In addition, an induction of tyrosine phosphorylation of numerous cellular proteins including ZO-1, E-cadherin, and beta-catenin, components of tight and adherens junctions, was observed. On the other hand, combined treatment of Caco-2 monolayers with H(2)O(2) and an NO donor (NOC5 or NOC12) relieved the damage to the barrier function and suppressed the protein tyrosine phosphorylation induced by H(2)O(2) alone. These results suggest that NO protects the barrier function of intestinal epithelia from oxidative stress by modulating some intracellular signaling pathways of protein tyrosine phosphorylation in epithelial cells. PMID:17451824

  19. Study of flow fields induced by surface dielectric barrier discharge actuator in low-pressure air

    SciTech Connect

    Che, Xueke E-mail: st@mail.iee.ac.cn; Nie, Wansheng; Tian, Xihui; Hou, Zhiyong; He, Haobo; Zhou, Penghui; Zhou, Siyin; Yang, Chao; Shao, Tao E-mail: st@mail.iee.ac.cn

    2014-04-15

    Surface dielectric barrier discharge (SDBD) is a promising method for a flow control. Flow fields induced by a SDBD actuator driven by the ac voltage in static air at low pressures varying from 1.0 to 27.7 kPa are measured by the particle image velocimetry method. The influence of the applied ac voltage frequency and magnitude on the induced flow fields is studied. The results show that three different classes of flow fields (wall jet flow field, complex flow field, and vortex-shape flow field) can be induced by the SDBD actuator in the low-pressure air. Among them, the wall jet flow field is the same as the tangential jet at atmospheric pressure, which is, together with the vertical jet, the complex flow field. The vortex-shape flow field is composed of one vertical jet which points towards the wall and two opposite tangential jets. The complex and the vortex-shape flow fields can be transformed to the wall jet flow field when the applied ac voltage frequency and magnitude are changed. It is found that the discharge power consumption increases initially, decreases, and then increases again at the same applied ac voltage magnitude when the air pressure decreases. The tangential velocity of the wall jet flow field increases when the air pressure decreases. It is however opposite for the complex flow field. The variation of the applied ac voltage frequency influences differently three different flow fields. When the applied ac voltage magnitude increases at the same applied ac voltage frequency, the maximal jet velocity increases, while the power efficiency increases only initially and then decreases again. The discharge power shows either linear or exponential dependences on the applied ac voltage magnitude.

  20. Lamin A precursor induces barrier-to-autointegration factor nuclear localization.

    PubMed

    Capanni, Cristina; Cenni, Vittoria; Haraguchi, Tokuko; Squarzoni, Stefano; Schüchner, Stefan; Ogris, Egon; Novelli, Giuseppe; Maraldi, Nadir; Lattanzi, Giovanna

    2010-07-01

    Lamin A, a protein component of the nuclear lamina, is synthesized as a precursor named prelamin A, whose multi-step maturation process involves different protein intermediates. As demonstrated in laminopathies such as familial partial lipodystrophy, mandibuloacral dysplasia, Werner syndrome, Hutchinson-Gilford progeria syndrome and restrictive dermopathy, failure of prelamin A processing results in the accumulation of lamin A protein precursors inside the nucleus which dominantly produces aberrant chromatin structure. To understand if nuclear lamina components may be involved in prelamin A chromatin remodeling effects, we investigated barrier-to-autointegration factor (BAF) localization and expression in prelamin A accumulating cells. BAF is a DNA-binding protein that interacts directly with histones, lamins and LEM-domain proteins and has roles in chromatin structure, mitosis and gene regulation. In this study, we show that the BAF heterogeneous localization between nucleus and cytoplasm observed in HEK293 cycling cells changes in response to prelamin A accumulation. In particular, we observed that the accumulation of lamin A, non-farnesylated prelamin A and farnesylated carboxymethylated lamin A precursors induce BAF nuclear translocation. Moreover, we show that the treatment of human fibroblasts with prelamin A interfering drugs results in similar changes. Finally, we report that the accumulation of progerin, a truncated form of farnesylated and carboxymethylated prelamin A identified in Hutchinson-Gilford progeria syndrome cells, induces BAF recruitment in the nucleus. These findings are supported by coimmunoprecipitation of prelamin A or progerin with BAF in vivo and suggest that BAF could mediate prelamin A-induced chromatin effects. PMID:20581439

  1. Reappraisal of flow to tile drains III. Drains with limited flow capacity

    NASA Astrophysics Data System (ADS)

    Khan, S.; Rushton, K. R.

    1996-09-01

    This third paper of the series on the reappraisal of flow to tile drains considers the time-variant situations in tile drain drainage systems when the quantity of water carried by tile drains is limited due to the capacity of the drains or the pumping equipment. Two categories of problem are analysed in this paper: (i) a series of parallel tile drains with a maximum specified flow and (ii) interceptor drains in the vicinity of canals. Complete details for satisfying the maximum specified flow conditions in tile drains are given. The effect of different capacities of tile drains on the performance of drainage system is explored.

  2. Dimethyl sulfoxide inhibits zymosan-induced intestinal inflammation and barrier dysfunction

    PubMed Central

    Li, Yu-Meng; Wang, Hai-Bin; Zheng, Jin-Guang; Bai, Xiao-Dong; Zhao, Zeng-Kai; Li, Jing-Yuan; Hu, Sen

    2015-01-01

    AIM: To investigate whether dimethyl sulfoxide (DMSO) inhibits gut inflammation and barrier dysfunction following zymosan-induced systemic inflammatory response syndrome and multiple organ dysfunction syndrome. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham with administration of normal saline (SS group); sham with administration of DMSO (SD group); zymosan with administration of normal saline (ZS group); and zymosan with administration of DMSO (ZD group). Each group contained three subgroups according to 4 h, 8 h, and 24 h after surgery. At 4 h, 8 h, and 24 h after intraperitoneal injection of zymosan (750 mg/kg), the levels of intestinal inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10] and oxides (myeloperoxidase, malonaldehyde, and superoxide dismutase) were examined. The levels of diamine oxidase (DAO) in plasma and intestinal mucosal blood flow (IMBF) were determined. Intestinal injury was also evaluated using an intestinal histological score and apoptosis of intestinal epithelial cells was determined by deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The intestinal epithelial tight junction protein, ZO-1, was observed by immunofluorescence. RESULTS: DMSO decreased TNF-α and increased IL-10 levels in the intestine compared with the ZS group at the corresponding time points. The activity of intestinal myeloperoxidase in the ZS group was higher than that in the ZD group 24 h after zymosan administration (P < 0.05). DMSO decreased the content of malondialdehyde (MDA) and increased the activity of superoxide dehydrogenase (SOD) 24 h after zymosan administration. The IMBF was lowest at 24 h and was 49.34% and 58.26% in the ZS group and ZD group, respectively (P < 0.05). DMSO alleviated injury in intestinal villi, and the gut injury score was significantly lower than the ZS group (3.6 ± 0.2 vs 4.2 ± 0.3, P < 0.05). DMSO decreased the level of DAO in plasma compared with the ZS

  3. HYDROGEN-RICH MEDIUM AMELIORATES LIPOPOLYSACCHARIDE-INDUCED BARRIER DYSFUNCTION VIA RHOA-MDIA1 SIGNALING IN CACO-2 CELLS

    PubMed Central

    Yang, Tao; Wang, Lu; Sun, Ruiqiang; Chen, Hongguang; Zhang, Hongtao; Yu, Yang; Wang, Yanyan; Wang, Guolin; Yu, Yonghao; Xie, Keliang

    2016-01-01

    ABSTRACT Gastrointestinal barrier dysfunction is associated with the severity and prognosis of sepsis. Hydrogen gas (H2) can ameliorate multiple organ damage in septic animals. Ras homolog gene family member A (RhoA) and mammalian diaphanous-related formin 1 (mDia1) are important to regulate tight junction (TJ) and adherens junction (AJ), both of which determine the integrity of the intestinal barrier. This study was aimed to investigate whether H2 could modulate lipopolysaccharide (LPS)-stimulated dysfunction of the intestinal barrier and whether RhoA-mDia1 signaling is involved. Caco-2 cells were exposed to different concentrations of LPS (1 μg/mL–1 mg/mL). The permeability of the intestinal barrier was evaluated by transepithelial resistance (TER) and fluorescein-isothiocyanate-dextran flux. Expression and distribution of occludin and E-cadherin were analyzed by Western blot and immunofluorescence. RhoA activity was measured by G-Lisa assay, and mDia1 expression was assessed by Western blot. LPS (100 μg/mL) decreased TER and increased fluorescein-isothiocyanate-dextran flux, which were alleviated by H2-rich medium. Also, H2 down-regulated LPS-induced oxidative stress. Moreover, H2 improved the down-regulated expression and redistribution of occludin and E-cadherin caused by LPS. Additionally, H2 alleviated LPS-caused RhoA activation, and the beneficial effects of H2 on barrier were counteracted by RhoA agonist CN03. Rho inhibitor C3 exoenzyme mitigated LPS-induced barrier breakdown. Furthermore, H2-rich medium increased mDia1 expression, and mDia1 knockdown abolished protections of H2 on barrier permeability. mDia1 knockdown eliminated H2-induced benefits for occludin and E-cadherin. These findings suggest that H2 improves LPS-induced hyperpermeability of the intestinal barrier and disruptions of TJ and AJ by moderating RhoA-mDia1 signaling. PMID:26529665

  4. Self-screening of the quantum confined Stark effect by the polarization induced bulk charges in the quantum barriers

    NASA Astrophysics Data System (ADS)

    Zhang, Zi-Hui; Liu, Wei; Ju, Zhengang; Tiam Tan, Swee; Ji, Yun; Kyaw, Zabu; Zhang, Xueliang; Wang, Liancheng; Wei Sun, Xiao; Volkan Demir, Hilmi

    2014-06-01

    InGaN/GaN light-emitting diodes (LEDs) grown along the polar orientations significantly suffer from the quantum confined Stark effect (QCSE) caused by the strong polarization induced electric field in the quantum wells, which is a fundamental problem intrinsic to the III-nitrides. Here, we show that the QCSE is self-screened by the polarization induced bulk charges enabled by designing quantum barriers. The InN composition of the InGaN quantum barrier graded along the growth orientation opportunely generates the polarization induced bulk charges in the quantum barrier, which well compensate the polarization induced interface charges, thus avoiding the electric field in the quantum wells. Consequently, the optical output power and the external quantum efficiency are substantially improved for the LEDs. The ability to self-screen the QCSE using polarization induced bulk charges opens up new possibilities for device engineering of III-nitrides not only in LEDs but also in other optoelectronic devices.

  5. Self-screening of the quantum confined Stark effect by the polarization induced bulk charges in the quantum barriers

    SciTech Connect

    Zhang, Zi-Hui; Liu, Wei; Ju, Zhengang; Tiam Tan, Swee; Ji, Yun; Kyaw, Zabu; Zhang, Xueliang; Wang, Liancheng; Wei Sun, Xiao E-mail: volkan@stanfordalumni.org; Volkan Demir, Hilmi E-mail: volkan@stanfordalumni.org

    2014-06-16

    InGaN/GaN light-emitting diodes (LEDs) grown along the polar orientations significantly suffer from the quantum confined Stark effect (QCSE) caused by the strong polarization induced electric field in the quantum wells, which is a fundamental problem intrinsic to the III-nitrides. Here, we show that the QCSE is self-screened by the polarization induced bulk charges enabled by designing quantum barriers. The InN composition of the InGaN quantum barrier graded along the growth orientation opportunely generates the polarization induced bulk charges in the quantum barrier, which well compensate the polarization induced interface charges, thus avoiding the electric field in the quantum wells. Consequently, the optical output power and the external quantum efficiency are substantially improved for the LEDs. The ability to self-screen the QCSE using polarization induced bulk charges opens up new possibilities for device engineering of III-nitrides not only in LEDs but also in other optoelectronic devices.

  6. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.

    PubMed

    Ling, Ka-Ho; Wan, Murphy Lam Yim; El-Nezami, Hani; Wang, Mingfu

    2016-05-16

    Contamination of food/feedstuffs by mycotoxins is a serious problem worldwide, causing severe economic losses and serious health problems in animals/humans. Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Grapes and red wine are rich in polyphenols, such as resveratrol (RES), which has striking antioxidant and anti-inflammatory activities. RES is a food-derived component; therefore, it may be simultaneously present with DON in the gastrointestinal tract. The aim of this study was to explore in vitro protective effects of RES against DON-induced intestinal damage. The results showed that RES could protect DON-induced bacteria translocation because of enhanced of intestinal barrier function by restoring the DON-induced decrease in transepithelial electrical resistance and increase in paracellular permeability. Further mechanistic studies demonstrated that RES protects against DON-induced barrier dysfunction by promoting the assembly of claudin-4 in the tight junction complex. This is probably mediated through modulation of IL-6 and IL-8 secretion via mitogen-activated protein kinase-dependent pathways. Our results imply that RES can protect against DON-induced intestinal damage and that RES may be used as a novel dietary intervention strategy to reduce DON toxicity in animals/humans. PMID:27058607

  7. Topical treatment with basic fibroblast growth factor promotes wound healing and barrier recovery induced by skin abrasion.

    PubMed

    Nakamizo, S; Egawa, G; Doi, H; Natsuaki, Y; Miyachi, Y; Kabashima, K

    2013-01-01

    It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery. PMID:23108135

  8. Heater drain system transient monitoring

    SciTech Connect

    Voll, B.J.; Farsaci, C.D.

    1995-12-01

    Feedwater heater drain systems are susceptible to unstable, two phase flow conditions. These instabilities are difficult to predict and are dependent on plant-specific system designs and operating conditions. Therefore, significant vibrations and transient events can occur that the systems are not specifically designed for. This paper describes how heater drain system responses due to unanticipated transient events at a nuclear plant were captured and quantified using a digital data acquisition system. The setup of the data acquisition system, including the determination of what parameters to monitor and how to effectively capture potential transient events, is discussed. This paper also discusses the monitoring results and their relevance to system modification evaluations and root cause evaluations.

  9. Generation of airborne listeria from floor drains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes can colonize floor drains in poultry processing and further processing facilities remaining even after cleaning and disinfection. Therefore, during wash down, workers exercise caution to prevent escape and transfer of drain microflora to food contact surfaces. The objective ...

  10. Transmigration of Neural Stem Cells across the Blood Brain Barrier Induced by Glioma Cells

    PubMed Central

    Díaz-Coránguez, Mónica; Segovia, José; López-Ornelas, Adolfo; Puerta-Guardo, Henry; Ludert, Juan; Chávez, Bibiana; Meraz-Cruz, Noemi; González-Mariscal, Lorenza

    2013-01-01

    Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2. PMID:23637756

  11. Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis

    PubMed Central

    Khounlotham, Manirath; Kim, Wooki; Peatman, Eric; Nava, Porfirio; Medina-Contreras, Oscar; Addis, Caroline; Koch, Stefan; Fournier, Benedicte; Nusrat, Asma; Denning, Timothy L.; Parkos, Charles A.

    2012-01-01

    SUMMARY Mice lacking Junctional Adhesion Molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis. To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r-/-Rag1-/- mice to acute colitis. Although negligible contributions of adaptive immunity in F11r-/-Rag1-/- mice were observed, F11r-/-Rag1-/- mice exhibited increased microflora-dependent colitis. Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-β-producing CD4+ T cells in F11r-/- mice. Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4+ T cells and TGF-β. Absence of IgA in F11r+/+Igha-/- mice did not affect disease whereas F11r-/-Igha-/- mice displayed markedly increased susceptibility to acute injury induced colitis. These data establish a role for adaptive immune mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise. PMID:22981539

  12. Direct and compound reactions induced by unstable helium beams near the Coulomb barrier

    NASA Astrophysics Data System (ADS)

    Navin, A.; Tripathi, V.; Blumenfeld, Y.; Nanal, V.; Simenel, C.; Casandjian, J. M.; de France, G.; Raabe, R.; Bazin, D.; Chatterjee, A.; Dasgupta, M.; Kailas, S.; Lemmon, R. C.; Mahata, K.; Pillay, R. G.; Pollacco, E. C.; Ramachandran, K.; Rejmund, M.; Shrivastava, A.; Sida, J. L.; Tryggestad, E.

    2004-10-01

    Reactions induced by radioactive 6,8 He beams from the SPIRAL facility were studied on 63,65 Cu and 188,190,192 Os targets and compared to reactions with the stable 4He projectiles from the Mumbai Pelletron. Partial residue cross sections for fusion and neutron transfer obtained from the measured intensities of characteristic in-beam γ rays for the 6He + 63,65 Cu systems are presented. Coincidence measurements of heavy reaction products, identified by their characteristic γ rays, with projectilelike charged particles, provide direct evidence for a large transfer cross section with Borromean nuclei 6He at 19.5 and 30 MeV and 8He at 27 MeV. Reaction cross sections were also obtained from measured elastic angular distributions for 6,8 He +Cu systems. Cross sections for fusion and direct reactions with 4,6 He beams on heavier targets of 188,192 Os at 30 MeV are also presented. The present work underlines the need to distinguish between various reaction mechanisms leading to the same products before drawing conclusions about the effect of weak binding on the fusion process. The feasibility of extracting small cross sections from inclusive in-beam γ -ray measurements for reaction studies near the Coulomb barrier with low intensity isotope separation on-line beams is highlighted.

  13. Direct and compound reactions induced by unstable helium beams near the Coulomb barrier

    SciTech Connect

    Navin, A.; Tripathi, V.; Chatterjee, A.; Kailas, S.; Mahata, K.; Ramachandran, K.; Shrivastava, A.; Blumenfeld, Y.; Tryggestad, E.; Nanal, V.; Pillay, R.G.; Simenel, C.; Casandjian, J.M.; France, G. de; Rejmund, M.; Raabe, R.; Pollacco, E.C.; Sida, J.L.; Dasgupta, M.

    2004-10-01

    Reactions induced by radioactive {sup 6,8}He beams from the SPIRAL facility were studied on {sup 63,65}Cu and {sup 188,190,192}Os targets and compared to reactions with the stable {sup 4}He projectiles from the Mumbai Pelletron. Partial residue cross sections for fusion and neutron transfer obtained from the measured intensities of characteristic in-beam {gamma} rays for the {sup 6}He+{sup 63,65}Cu systems are presented. Coincidence measurements of heavy reaction products, identified by their characteristic {gamma} rays, with projectilelike charged particles, provide direct evidence for a large transfer cross section with Borromean nuclei {sup 6}He at 19.5 and 30 MeV and {sup 8}He at 27 MeV. Reaction cross sections were also obtained from measured elastic angular distributions for {sup 6,8}He+Cu systems. Cross sections for fusion and direct reactions with {sup 4,6}He beams on heavier targets of {sup 188,192}Os at 30 MeV are also presented. The present work underlines the need to distinguish between various reaction mechanisms leading to the same products before drawing conclusions about the effect of weak binding on the fusion process. The feasibility of extracting small cross sections from inclusive in-beam {gamma}-ray measurements for reaction studies near the Coulomb barrier with low intensity isotope separation on-line beams is highlighted.

  14. Electroconvective Instability in Flow-shear-induced Transport Barrier: Threshold for Stable Vortices and Chaotic Eddies

    NASA Astrophysics Data System (ADS)

    Kwak, Rhokyun; Pham, Van Sang; Han, Jongyoon

    2014-11-01

    Suppression of turbulence and transport by shear flow is a common process in plasma fluid dynamics, while it has been rarely observed in nonionized fluids. Here, we visualize this effect in microfluidic nonionized system with electroconvective instability (EC) initiated by ion concentration polarization on ion selective membrane. The membranes act as the source of both instability and flow shear (wall shear of Hagen-Poiseuille (HP) flow) simultaneously, fitting the requisite for this shear suppression effect; turbulence in the domain of flow shear. To the best of our knowledge, this is the first characterization of flow-shear-induced transport barrier in microfluidics, captured by scaling analysis, experiment, and numerical modeling. Selected by balancing flow shear and velocity fluctuation, which generated by HP flow and vortical EC, the threshold for shear suppression scales by EC thickness dec/ w < 0.618. Stable unidirectional EC occurs under the threshold, while chaotic EC occurs over the threshold by overcoming flow shear. It also has significant implications on the energy saving of electrochemical systems (e . g . electrodialysis) to prevent chaotic turbulences and corresponding energy dissipations. This work was supported by the Advanced Research Projects Agency-Energy Grant (DE-AR0000294).

  15. Saffman-Taylor-like instability in a narrow gap induced by dielectric barrier discharge.

    PubMed

    Hou, Shang-Yan; Chu, Hong-Yu

    2015-07-01

    This work is inspired by the expansion of the plasma bubble in a narrow gap reported by Chu and Lee [Phys. Rev. Lett. 107, 225001 (2011)]. We report the unstable phenomena of the plasma-liquid interface with different curvature in a Hele-Shaw cell. Dielectric barrier discharge is produced in the cell at atmospheric pressure which is partially filled with silicone oil. We show that the Saffman-Taylor-like instability is observed on the bubble-type, channel-type, and drop-type interfaces. The Schlieren observation of the plasma-drop interaction reveals that there is a vapor layer around the drop and the particle image velocimetry shows the liquid flow inside the drop. We propose that the thermal Marangoni effect induced by the plasma heating is responsible for the unstable phenomena of the plasma-liquid interaction. The fluctuation of the interface is shown consistently with the Saffman-Taylor instability modified by the temperature-dependent velocity and surface tension. PMID:26274288

  16. Evaluation of pathogen inactivation on sliced cheese induced by encapsulated atmospheric pressure dielectric barrier discharge plasma.

    PubMed

    Yong, Hae In; Kim, Hyun-Joo; Park, Sanghoo; Alahakoon, Amali U; Kim, Kijung; Choe, Wonho; Jo, Cheorun

    2015-04-01

    Pathogen inactivation induced by atmospheric pressure dielectric barrier discharge (DBD) (250 W, 15 kHz, air discharge) produced in a rectangular plastic container and the effect of post-treatment storage time on inactivation were evaluated using agar plates and cheese slices. When agar plates were treated with plasma, populations of Escherichia coli, Salmonella Typhimurium, and Listeria monocytogenes showed 3.57, 6.69, and 6.53 decimal reductions at 60 s, 45 s, and 7 min, respectively. When the pathogens tested were inoculated on cheese slices, 2.67, 3.10, and 1.65 decimal reductions were achieved at the same respective treatment times. The post-treatment storage duration following plasma treatment potently affected further reduction in pathogen populations. Therefore, the newly developed encapsulated DBD-plasma system for use in a container can be applied to improve the safety of sliced cheese, and increasing post-treatment storage time can greatly enhance the system's pathogen-inactivation efficiency. PMID:25475265

  17. Microbubble Type and Distribution Dependence of Focused Ultrasound Induced Blood Brain Barrier Opening

    PubMed Central

    Wang, Shutao; Samiotaki, Gesthimani; Olumolade, Oluyemi; Feshitan, Jameel A.; Konofagou, Elisa E.

    2014-01-01

    Focused Ultrasound (FUS) in the presence of microbubbles has been used to non-invasively induce reversible blood brain barrier (BBB) opening in both rodents and non-human primates. This study aims at identifying the dependence of the BBB opening properties on the polydisperse microbubble (since all clinically approved microbubbles are polydisperse) type and distribution by using clinically approved UCA (Definity®) and in-house made polydisperse microbubbles (IHP) in mice. A total of 18 C57BL/6 mice (n = 3) were used in this study, and each mouse received either Definity® or IHP microbubbles via tail vein injection. The concentration and size distribution of both the activated Definity® and IHP microbubbles were measured and diluted to 6×108/ml prior to injection. Immediately after the microbubble administration, FUS sonications were carried out with the following parameters: frequency of 1.5 MHz, pulse repetition frequency of 10 Hz, 1000 cycles, in situ peak rarefactional acoustic pressures of 0.3 MPa, 0.45 MPa, and 0.6 MPa for a sonication duration of 60 s. Contrast-enhanced magnetic resonance imaging (MRI) was used to confirm the BBB opening and allowed for image-based analysis. The permeability of the treated region and volumes of BBB opening using the two types of microbubbles did not show significant difference (P > 0.05) for PRPs of 0.45 MPa and 0.6 MPa, while IHP microbubbles showed significantly higher permeability and volume of opening (P < 0.05) at the relatively lower pressure of 0.3 MPa. The results from this study indicate that the microbubble type and distribution could have significant effects on the FUS-induced BBB opening at lower, but less important at higher, pressure levels, possibly due to the stable cavitation that governs the former. This difference may have become less significant at higher FUS pressure levels where inertial cavitation typically occurs. PMID:24239362

  18. A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption

    PubMed Central

    Sharabi, Shirley; Kos, Bor; Last, David; Guez, David; Daniels, Dianne; Harnof, Sagi; Miklavcic, Damijan

    2016-01-01

    Background Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning. Material and methods Cell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments. Results Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r2 = 0.79; p < 0.008, r2 = 0.91; p < 0.001). The results presented a strong plateau effect as the pulse number increased. The ratio between complete cell death and no cell death thresholds was relatively narrow (between 0.88-0.91) even for small numbers of pulses and depended weakly on the number of pulses. For BBB disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes. Conclusions The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup. PMID:27069447

  19. Dissipated power and induced velocity fields data of a micro single dielectric barrier discharge plasma actuator for active flow control☆

    PubMed Central

    Pescini, E.; Martínez, D.S.; De Giorgi, M.G.; Francioso, L.; Ficarella, A.

    2015-01-01

    In recent years, single dielectric barrier discharge (SDBD) plasma actuators have gained great interest among all the active flow control devices typically employed in aerospace and turbomachinery applications [1,2]. Compared with the macro SDBDs, the micro single dielectric barrier discharge (MSDBD) actuators showed a higher efficiency in conversion of input electrical power to delivered mechanical power [3,4]. This article provides data regarding the performances of a MSDBD plasma actuator [5,6]. The power dissipation values [5] and the experimental and numerical induced velocity fields [6] are provided. The present data support and enrich the research article entitled “Optimization of micro single dielectric barrier discharge plasma actuator models based on experimental velocity and body force fields” by Pescini et al. [6]. PMID:26425667

  20. 21 CFR 884.3200 - Cervical drain.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cervical drain. 884.3200 Section 884.3200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... drain. (a) Identification. A cervical drain is a device designed to provide an exit channel for...

  1. 21 CFR 884.3200 - Cervical drain.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cervical drain. 884.3200 Section 884.3200 Food and... OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Prosthetic Devices § 884.3200 Cervical drain. (a) Identification. A cervical drain is a device designed to provide an exit channel for...

  2. Barrier protective effects of withaferin A in HMGB1-induced inflammatory responses in both cellular and animal models

    SciTech Connect

    Lee, Wonhwa; Kim, Tae Hoon; Ku, Sae-Kwang; Min, Kyoung-jin; Lee, Hyun-Shik; Kwon, Taeg Kyu; Bae, Jong-Sup

    2012-07-01

    Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. In this study, we first investigated the possible barrier protective effects of WFA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice induced by high mobility group box 1 protein (HMGB1) and the associated signaling pathways. The barrier protective activities of WFA were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that WFA inhibited lipopolysaccharide (LPS)-induced HMGB1 release and HMGB1-mediated barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of leukocytes to human endothelial cells. WFA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that WFA suppressed the production of interleukin 6, tumor necrosis factor-α (TNF-α) and activation of nuclear factor-κB (NF-κB) by HMGB1. Collectively, these results suggest that WFA protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. -- Highlights: ► Withaferin A inhibited LPS induced HMGB1 release. ► Withaferin A reduced HMGB1-mediated hyperpermeability. ► Withaferin A inhibited HMGB1-mediated adhesion and migration of leukocytes. ► Withaferin A inhibited HMGB1-mediated activation of NF-κB, IL-6 and TNF-α.

  3. Prostacyclin post-treatment improves LPS-induced acute lung injury and endothelial barrier recovery via Rap1

    PubMed Central

    Birukova, Anna A.; Meng, Fanyong; Tian, Yufeng; Meliton, Angelo; Sarich, Nicolene; Quilliam, Lawrence A.; Birukov, Konstantin G.

    2015-01-01

    Protective effects of prostacyclin (PC) or its stable analog beraprost against agonist-induced lung vascular inflammation have been associated with elevation of intracellular cAMP and Rac GTPase signaling which inhibited the RhoA GTPase-dependent pathway of endothelial barrier dysfunction. This study investigated a distinct mechanism of PC-stimulated lung vascular endothelial (EC) barrier recovery and resolution of LPS-induced inflammation mediated by small GTPase Rap1. Efficient barrier recovery was observed in LPS-challenged pulmonary EC after prostacyslin administration even after 15 hrs of initial inflammatory insult and was accompanied by the significant attenuation of p38 MAP kinase and NFkB signaling and decreased production of IL-8 and soluble ICAM1. These effects were reproduced in cells post-treated with 8CPT, a small molecule activator of Rap1-specific nucleotide exchange factor Epac. By contrast, pharmacologic Epac inhibitor, Rap1 knockdown, or knockdown of cell junction-associated Rap1 effector afadin attenuated EC recovery caused by PC or 8CPT post-treatment. The key role of Rap1 in lung barrier restoration was further confirmed in the murine model of LPS-induced acute lung injury. Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count, and Evans blue extravasation and live imaging of vascular leak over 6 days using a fluorescent tracer. The data showed significant acceleration of lung recovery by PC and 8CPT post-treatment, which was abrogated in Rap1a−/− mice. These results suggest that post-treatment with PC triggers the Epac/Rap1/afadin-dependent mechanism of endothelial barrier restoration and downregulation of p38MAPK and NFkB inflammatory cascades, altogether leading to accelerated lung recovery. PMID:25545047

  4. An improved performance of copper phthalocyanine OFETs with channel and source/drain contact modifications

    NASA Astrophysics Data System (ADS)

    Huanqin, Dang; Xiaoming, Wu; Xiaowei, Sun; Runqiu, Zou; Ruochuan, Zhang; Shougen, Yin

    2015-10-01

    We report an effective method to improve the performance of p-type copper phthalocyanine (CuPc) based organic field-effect transistors (OFETs) by employing a thin para-quaterphenyl (p-4p) film and simultaneously applying V2O5 to the source/drain regions. The p-4p layer was inserted between the insulating layer and the active layer, and V2O5 layer was added between CuPc and Al in the source-drain (S/D) area. As a result, the field-effect saturation mobility and on/off current ratio of the optimized device were improved to 5 × 10-2 cm2/(V·s) and 104, respectively. We believe that because p-4p could induce CuPc to form a highly oriented and continuous film, this resulted in the better injection and transport of the carriers. Moreover, by introducing the V2O5 electrode's modified layers, the height of the carrier injection barrier could be effectively tuned and the contact resistance could be reduced. Project supported by the National Natural Science Foundation of China (No. 60676051), the National High Technology Research and Development Program of China (No. 2013A A014201), the Scientific Developing Foundation of Tianjin Education Commission (No. 2011ZD02), the Key Science and Technology Support Program of Tianjin (No. 14ZCZDGX00006), and the Foundation of Key Discipline of Material Physics and Chemistry of Tianjin.

  5. Drain current modulation in a nanoscale field-effect-transistor channel by single dopant implantation

    NASA Astrophysics Data System (ADS)

    Johnson, B. C.; Tettamanzi, G. C.; Alves, A. D. C.; Thompson, S.; Yang, C.; Verduijn, J.; Mol, J. A.; Wacquez, R.; Vinet, M.; Sanquer, M.; Rogge, S.; Jamieson, D. N.

    2010-06-01

    We demonstrate single dopant implantation into the channel of a silicon nanoscale metal-oxide-semiconductor field-effect-transistor. This is achieved by monitoring the drain current modulation during ion irradiation. Deterministic doping is crucial for overcoming dopant number variability in present nanoscale devices and for exploiting single atom degrees of freedom. The two main ion stopping processes that induce drain current modulation are examined. We employ 500 keV He ions, in which electronic stopping is dominant, leading to discrete increases in drain current and 14 keV P dopants for which nuclear stopping is dominant leading to discrete decreases in drain current.

  6. Safety drain system for fluid reservoir

    NASA Technical Reports Server (NTRS)

    England, John Dwight (Inventor); Kelley, Anthony R. (Inventor); Cronise, Raymond J. (Inventor)

    2012-01-01

    A safety drain system includes a plurality of drain sections, each of which defines distinct fluid flow paths. At least a portion of the fluid flow paths commence at a side of the drain section that is in fluid communication with a reservoir's fluid. Each fluid flow path at the side communicating with the reservoir's fluid defines an opening having a smallest dimension not to exceed approximately one centimeter. The drain sections are distributed over at least one surface of the reservoir. A manifold is coupled to the drain sections.

  7. Analytical Modeling of Potential Distribution and Threshold Voltage of Gate Underlap DG MOSFETs with a Source/Drain Lateral Gaussian Doping Profile

    NASA Astrophysics Data System (ADS)

    Singh, Kunal; Kumar, Mirgender; Goel, Ekta; Singh, Balraj; Dubey, Sarvesh; Kumar, Sanjay; Jit, Satyabrata

    2016-04-01

    This paper reports a new two-dimensional (2D) analytical model for the potential distribution and threshold voltage of the short-channel symmetric gate underlap ultrathin DG MOSFETs with a lateral Gaussian doping profile in the source (S)/drain (D) region. The parabolic approximation and conformal mapping techniques have been explored for solving the 2D Poisson's equation to obtain the channel potential function of the device. The effects of straggle parameter (of the lateral Gaussian doping profile in the S/D region), underlap length, gate length, channel thickness and oxide thickness on the surface potential and threshold voltage have been investigated. The loss of switching speed due to the drain-induced barrier lowering (DIBL) has also been reported. The proposed model results have been validated by comparing them with their corresponding TCAD simulation data obtained by using the commercially available 2D ATLAS™ simulation software.

  8. Contact induced spin relaxation in graphene spin valves with Al2O3 and MgO tunnel barriers

    NASA Astrophysics Data System (ADS)

    Amamou, Walid; Lin, Zhisheng; van Baren, Jeremiah; Turkyilmaz, Serol; Shi, Jing; Kawakami, Roland K.

    2016-03-01

    We investigate spin relaxation in graphene by systematically comparing the roles of spin absorption, other contact-induced effects (e.g., fringe fields), and bulk spin relaxation for graphene spin valves with MgO barriers, Al2O3 barriers, and transparent contacts. We obtain effective spin lifetimes by fitting the Hanle spin precession data with two models that include or exclude the effect of spin absorption. Results indicate that additional contact-induced spin relaxation other than spin absorption dominates the contact effect. For tunneling contacts, we find reasonable agreement between the two models with median discrepancy of ˜20% for MgO and ˜10% for Al2O3.

  9. Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species

    PubMed Central

    Arjunan, Krishna Priya; Friedman, Gary; Fridman, Alexander; Clyne, Alisa Morss

    2012-01-01

    Vascularization plays a key role in processes such as wound healing and tissue engineering. Non-thermal plasma, which primarily produces reactive oxygen species (ROS), has recently emerged as an efficient tool in medical applications including blood coagulation, sterilization and malignant cell apoptosis. Liquids and porcine aortic endothelial cells were treated with a non-thermal dielectric barrier discharge plasma in vitro. Plasma treatment of phosphate-buffered saline (PBS) and serum-free medium increased ROS concentration in a dose-dependent manner, with a higher concentration observed in serum-free medium compared with PBS. Species concentration inside cells peaked 1 h after treatment, followed by a decrease 3 h post treatment. Endothelial cells treated with a plasma dose of 4.2 J cm–2 had 1.7 times more cells than untreated samples 5 days after plasma treatment. The 4.2 J cm–2 plasma dose increased two-dimensional migration distance by 40 per cent compared with untreated control, while the number of cells that migrated through a three-dimensional collagen gel increased by 15 per cent. Tube formation was also enhanced by plasma treatment, with tube lengths in plasma-treated samples measuring 2.6 times longer than control samples. A fibroblast growth factor-2 (FGF-2) neutralizing antibody and ROS scavengers abrogated these angiogenic effects. These data indicate that plasma enhanced proliferation, migration and tube formation is due to FGF-2 release induced by plasma-produced ROS. Non-thermal plasma may be used as a potential tool for applying ROS in precise doses to enhance vascularization. PMID:21653568

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

    SciTech Connect

    Wang Qiang; Luo Wenjing; Zheng Wei; Liu Yiping; Xu Hui; Zheng Gang; Dai Zhongming; Zhang Wenbin; Chen Yaoming; Chen Jingyuan . E-mail: jy_chen@fmmu.edu.cn

    2007-02-15

    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 {mu}g 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{sub 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.

  11. Activation of toll like receptor-3 induces corneal epithelial barrier dysfunction.

    PubMed

    Wei, Jie; Jiang, Hua; Gao, Hongrui; Wang, Guangjie

    2015-06-01

    The epithelial barrier is critical in the maintenance of the homeostasis of the cornea. A number of eye disorders are associated with the corneal epithelial barrier dysfunction. Viral infection is one common eye disease type. This study aims to elucidate the mechanism by which the activation of toll like receptor 3 (TLR3) in the disruption of the corneal epithelial barrier. In this study, HCE cells (a human corneal epithelial cell line) were cultured into epithelial layers using as an in vitro model of the corneal epithelial barrier. PolyI:C was used as a ligand of TLR3. The transepithelial electric resistance (TER) and permeability of the HCE epithelial layer were assessed using as the parameters to evaluate the corneal epithelial barrier integrity. The results showed that exposure to PolyI:C markedly decreased the TER and increased the permeability of the HCE epithelial layers; the levels of cell junction protein, E-cadherin, were repressed by PolyI:C via increasing histone deacetylase-1 (HDAC1), the latter binding to the promoter of E-cadherin and repressed the transcription of E-cadherin. The addition of butyrate (an inhibitor of HDAC1) to the culture blocked the corneal epithelial barrier dysfunction caused by PolyI:C. In conclusion, activation of TLR3 can disrupt the corneal epithelial barrier, which can be blocked by the inhibitor of HDAC1. PMID:25912142

  12. Investigation of contribution of incomplete fusion in the total fusion process induced by 9Be on 181Ta target at near barrier energies

    NASA Astrophysics Data System (ADS)

    Kharab, Rajesh; Chahal, Rajiv; Kumar, Rajiv

    2016-02-01

    We have studied the relative contribution of incomplete fusion (ICF) and complete fusion (CF) in total fusion (TF) induced by 9Be on 181Ta target at energies in the vicinity of Coulomb barrier using classical dynamical model and Wong's formula in conjugation with energy dependent Woods-Saxon formula. It is found that at above barrier energies ICF contributes almost 30% in TF while at energies below the barrier qualitatively its contribution is much more than thirty percent.

  13. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    SciTech Connect

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Lee, Seung-Sook; Park, Sunhoo

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  14. Baicalein induces CD4+Foxp3+ T cells and enhances intestinal barrier function in a mouse model of food allergy

    PubMed Central

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Kwon, Da-Ae; Shon, Dong-Hwa

    2016-01-01

    The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID:27561877

  15. Baicalein induces CD4(+)Foxp3(+) T cells and enhances intestinal barrier function in a mouse model of food allergy.

    PubMed

    Bae, Min-Jung; Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Kwon, Da-Ae; Shon, Dong-Hwa

    2016-01-01

    The incidence of food allergy, which is triggered by allergen permeation of the gastrointestinal tract followed by a T-helper (Th) 2-mediated immune response, has been increasing annually worldwide. We examined the effects of baicalein (5,6,7-trihydroxyflavone), a flavonoid from Scutellaria baicalensis used in oriental herbal medicine, on regulatory T (Treg) cell induction and intestinal barrier function through the regulation of tight junctions in a mouse model of food allergy. An allergic response was induced by oral challenge with ovalbumin, and the incidence of allergic symptoms and T cell-related activity in the mesenteric lymph nodes were analyzed with and without the presence of baicalein. Our results demonstrated that the administration of baicalein ameliorated the symptoms of food allergy and attenuated serum IgE and effector T cells. However, Treg-related factors were up-regulated by baicalein. Furthermore, baicalein was shown to enhance intestinal barrier function through the regulation of tight junctions. We also found that baicalein treatment induced the differentiation of Treg cells via aryl hydrocarbon receptors (AhRs). Thus, the action of baicalein as an agonist of AhR can induce Treg differentiation and enhance barrier function, suggesting that baicalein might serve as an effective immune regulator derived from foods for the treatment of food allergy. PMID:27561877

  16. Hypo-osmotic shock-induced subclinical inflammation of skin in a rat model of disrupted skin barrier function.

    PubMed

    Kishi, Chihiro; Minematsu, Takeo; Huang, Lijuan; Mugita, Yuko; Kitamura, Aya; Nakagami, Gojiro; Yamane, Takumi; Yoshida, Mikako; Noguchi, Hiroshi; Funakubo, Megumi; Mori, Taketoshi; Sanada, Hiromi

    2015-03-01

    Aging disrupts skin barrier function and induces xerosis accompanied by pruritus. In many cases, elderly patients complain of pruritus during skin hygiene care, a condition called aquagenic pruritus of the elderly (APE). To date, the pathophysiology and mechanism of action of APE have not been elucidated. We conducted the present study to test the hypothesis that hypo-osmotic shock of epidermal cells induces skin inflammation and elongation of C-fibers by nerve growth factor β (NGFβ) as a basic mechanism of APE. The dorsal skin of HWY rats, which are a model for disrupted skin barrier function, was treated with distilled water (hypotonic treatment [Hypo] group) or normal saline (isotonic treatment [Iso] group) by applying soaked gauze for 7 days. Untreated rats were used as a control (no-treatment [NT] group). Histochemical and immunohistochemical analyses revealed inflammatory responses in the epidermis and the dermal papillary layer in the Hypo group, while no alterations were observed in the Iso or NT groups. Induction of expression and secretion of NGFβ and elongation of C-fibers into the epidermis were found in the Hypo group. In contrast, secretion of NGFβ was significantly lower and elongation of C-fibers was not observed in the Iso group. These results suggest that hypo-osmotic shock-induced inflammatory reactions promote hypersensitivity to pruritus in skin with disrupted barrier function. PMID:25681269

  17. Novel Peptide for Attenuation of Hyperoxia-induced Disruption of Lung Endothelial Barrier and Pulmonary Edema via Modulating Peroxynitrite Formation*

    PubMed Central

    Kondrikov, Dmitry; Gross, Christine; Black, Stephen M.; Su, Yunchao

    2014-01-01

    Pulmonary damages of oxygen toxicity include vascular leakage and pulmonary edema. We have previously reported that hyperoxia increases the formation of NO and peroxynitrite in lung endothelial cells via increased interaction of endothelial nitric oxide (eNOS) with β-actin. A peptide (P326TAT) with amino acid sequence corresponding to the actin binding region of eNOS residues 326–333 has been shown to reduce the hyperoxia-induced formation of NO and peroxynitrite in lung endothelial cells. In the present study, we found that exposure of pulmonary artery endothelial cells to hyperoxia (95% oxygen and 5% CO2) for 48 h resulted in disruption of monolayer barrier integrity in two phases, and apoptosis occurred in the second phase. NOS inhibitor NG-nitro-l-arginine methyl ester attenuated the endothelial barrier disruption in both phases. Peroxynitrite scavenger uric acid did not affect the first phase but ameliorated the second phase of endothelial barrier disruption and apoptosis. P326TAT inhibited hyperoxia-induced disruption of monolayer barrier integrity in two phases and apoptosis in the second phase. More importantly, injection of P326TAT attenuated vascular leakage, pulmonary edema, and endothelial apoptosis in the lungs of mice exposed to hyperoxia. P326TAT also significantly reduced the increase in eNOS-β-actin association and protein tyrosine nitration. Together, these results indicate that peptide P326TAT ameliorates barrier dysfunction of hyperoxic lung endothelial monolayer and attenuates eNOS-β-actin association, peroxynitrite formation, endothelial apoptosis, and pulmonary edema in lungs of hyperoxic mice. P326TAT can be a novel therapeutic agent to treat or prevent acute lung injury in oxygen toxicity. PMID:25315770

  18. MR assessment of radiation-induced blood-brain barrier permeability changes in a rat glioma model

    SciTech Connect

    Krueck, W.G. Univ. of Washington School of Medicine, Seattle, WA ); Schmiedl, U.P.; Maravilla, K.R.; Starr, F.L.; Kenney, J. )

    1994-04-01

    To assess the potential of a T1-weighted, gadolinium-enhanced MR technique for quantifying radiation-induced changes of blood-brain barrier permeability in a model of stereotactically implanted intracerebral gliomas in rats. We calculated the gadolinium blood-to-tissue transport coefficient for gadopentetate dimeglumine from signal intensities in sequential MR images in nine control animals that were not irradiated and in five and three animals that had received 2500 cGy and 1500 cGy whole-brain irradiation, respectively, at 2 days before imaging. The average blood-to-tissue transport coefficient values were 9.76 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the control group, 23.41 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the 2500-cGy group, and 25.63 mL[center dot]kg[sup [minus]1][center dot]min[sup [minus]1] in the 1500-cGy group. Blood-to-tissue transport coefficients were significantly higher after irradiation, indicating increased radiation-induced blood-brain barrier permeability. Similar increased blood-brain barrier leakiness in brain tumors after high-dose irradiation has been shown by previous nuclear medicine studies using quantitative autoradiography. Contrast-enhanced dynamic MR of brain gliomas is a sensitive method to document radiation-induced blood-brain barrier breakdown. Quantitative gadolinium-enhanced MR may become a useful tool for the management of patients with brain tumors undergoing radiation therapy. 28 refs., 4 figs., 1 tab.

  19. Burn-induced gut barrier injury is attenuated by phosphodiesterase inhibition: effects on tight junction structural proteins.

    PubMed

    Costantini, Todd W; Loomis, William H; Putnam, James G; Drusinsky, Dana; Deree, Jessica; Choi, Sunghyuk; Wolf, Paul; Baird, Andrew; Eliceiri, Brian; Bansal, Vishal; Coimbra, Raul

    2009-04-01

    Loss of intestinal barrier function after burn injury allows movement of intraluminal contents across the mucosa, which can lead to the development of distant organ injury and multiple organ failure. Tight junction function is highly regulated by membrane-associated proteins including occludin and zonula occludens protein 1 (ZO-1), which can be modulated by systemic inflammation. We hypothesized that (1) burn injury leads to gut barrier injury, and (2) phosphodiesterase inhibition will attenuate these burn-induced changes. Male balb/c mice undergoing a 30% steam burn were randomized to resuscitation with normal saline or normal saline + pentoxifylline (PTX; 12.5 mg/kg). Intestinal injury was assessed by histological diagnosis and TNF-alpha levels using enzyme-linked immunosorbent assay. Intestinal permeability was assessed by measuring the plasma concentration of fluorescein isothiocyanate-dextran after intraluminal injection in the distal ileum. Occludin and ZO-1 levels were analyzed by immunoblotting and immunohistochemistry. Thirty percent total body surface area (TBSA) burn results in a significant increase in intestinal permeability. Treatment with PTX after burn attenuates intestinal permeability to sham levels. Burn injury resulted in a marked decrease in the levels of tight junction proteins occludin and ZO-1 at 6 and 24 h. The use of PTX after burn significantly decreases the breakdown of occludin and ZO-1. Pentoxifylline also attenuates the burn-induced increase in plasma and intestinal TNF-alpha. Confocal microscopy demonstrates that PTX attenuates the burn-induced reorganization of occludin and ZO-1 away from the tight junction. Pentoxifylline attenuates burn-induced intestinal permeability and decreases the breakdown and reorganization of intestinal occludin and ZO-1. Therefore, phosphodiesterase inhibition may be a useful adjunct strategy in the attenuation of burn-induced gut barrier injury. PMID:18791495

  20. A case of a retained drain tip following intercostal drain insertion: avoiding a 'never event'.

    PubMed

    Oswald, Nicola K; Abdelaziz, Mahmoud; Rajesh, Pala B; Steyn, Richard S

    2016-01-01

    Pleural effusions are commonly drained with Seldinger intercostal drains. One uncommon but serious risk of drain insertion is that of a foreign body being retained in the pleural cavity following removal. We report a case in which the tip of the drain was retained in the pleural space following difficult insertion of a Seldinger intercostal drain in a district general hospital. Prompt recognition and clear patient communication are important at the occurrence of an unusual complication. Surgical removal of the foreign body was performed following transfer. We report this case to raise awareness that insertion and withdrawal of drains over the guidewire during insertion may damage the drain and highlight the need for doctors who insert chest drains to perform a count of instruments during ward or clinic-based procedures as well as those performed in theatres. We now include removable parts of chest drains in our theatre instrument count. PMID:27076623

  1. Blood-brain barrier alteration after microwave-induced hyperthermia is purely a thermal effect: I. Temperature and power measurements

    SciTech Connect

    Moriyama, E.; Salcman, M.; Broadwell, R.D. )

    1991-03-01

    The effect of microwave-induced hyperthermia on the blood-brain barrier was studied in 21 Sprague-Dawley rats. Under sodium pentobarbital anesthesia, animals were place in a stereotactic frame, and an interstitial microwave antenna operating at 2450 MHz was inserted in a bony groove drilled parallel to the sagittal suture. Some antennae were equipped with an external cooling jacket. Temperature measurements were made lateral to the antenna by fluoroptical thermometry, and power was calculated from the time-temperature profile. Five minutes prior to termination of microwave irradiation, horseradish peroxidase (1 mg/20 g body weight) was injected intravenously. Extravasation of horseradish peroxidase was observed in brain tissue heated above 44.3 degrees C for 30 minutes and at 42.5 degrees C for 60 minutes. Microwave irradiation failed to open the blood-brain barrier when brain temperatures were sustained below 40.3 degrees C by the cooling system. Extravasation of blood-borne peroxidase occurred at sites of maximal temperature elevation, even when these did not coincide with the site of maximum power density. The data suggest that microwave-induced hyperthermia is an effective means for opening the blood-brain barrier and that the mechanism is not related to the nonthermal effect of microwaves.

  2. STAT1 signaling modulates HIV-1-induced inflammatory responses and leukocyte transmigration across the blood-brain barrier.

    PubMed

    Chaudhuri, Anathbandhu; Yang, Bo; Gendelman, Howard E; Persidsky, Yuri; Kanmogne, Georgette D

    2008-02-15

    The relationship among neuroinflammation, blood-brain barrier (BBB) dysfunction, and progressive HIV-1 infection as they affect the onset and development of neuroAIDS is incompletely understood. One possible link is signal transducers and activators of transcription (STATs) pathways. These respond to proinflammatory and regulatory factors and could affect neuroinflammatory responses induced from infected cells and disease-affected brain tissue. Our previous works demonstrated that HIV-1 activates pro-inflammatory and interferon-alpha-inducible genes in human brain microvascular endothelial cells (HBMECs) and that these genes are linked to the Janus kinase (JAK)/STAT pathway. We now demonstrate that HIV-1 activates STAT1, induces IL-6 expression, and diminishes expression of claudin-5, ZO-1, and ZO-2 in HBMECs. The STAT1 inhibitor, fludarabine, blocked HIV-1-induced IL-6, diminished HIV-1-induced claudin-5 and ZO-1 down-regulation, and blocked HIV-1- and IL-6-induced monocyte migration across a BBB model. Enhanced expression and activation of STAT1 and decreased claudin-5 were observed in microvessels from autopsied brains of patients with HIV-1-associated dementia. These data support the notion that STAT1 plays an integral role in HIV-1-induced BBB damage and is relevant to viral neuropathogenesis. Inhibition of STAT1 activation could provide a unique therapeutic strategy to attenuate HIV-1-induced BBB compromise and as such improve clinical outcomes. PMID:18003888

  3. Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin.

    PubMed

    Ishii, Yuki; Sugimoto, Saho; Izawa, Naoki; Sone, Toshiro; Chiba, Katsuyoshi; Miyazaki, Kouji

    2014-07-01

    Recent studies have shown that some probiotics affect not only the gut but also the skin. However, the effects of probiotics on ultraviolet (UV)-induced skin damage are poorly understood. In this study, we aim to examine whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, can attenuate skin barrier perturbation caused by UV and reactive oxygen species (ROS) in hairless mice. The mice were orally supplemented with a vehicle only or BBY once a day for nine successive days. Mouse dorsal skin was irradiated with UV from days 6 to 9. The day after the final irradiation, the transepidermal water loss (TEWL), stratum corneum hydration, and oxidation-related factors of the skin were evaluated. We elucidated that BBY prevented the UV-induced increase in TEWL and decrease in stratum corneum hydration. In addition, BBY significantly suppressed the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and lipids, and xanthine oxidase activity in the skin. Conversely, antioxidant capacity did not change regardless of whether BBY was administered or not. In parameters we evaluated, there was a positive correlation between the increase in TEWL and the oxidation levels of proteins and lipids. Our results suggest that oral administration of BBY attenuates UV-induced barrier perturbation and oxidative stress of the skin, and this antioxidative effect is not attributed to enhancement of antioxidant capacity but to the prevention of ROS generation. PMID:24414333

  4. Cardiovascular collapse with attempted pericardial drain withdrawal

    PubMed Central

    Kraus, Molly B; Spitznagel, Rachel A; Kugler, Jane A

    2016-01-01

    Cardiac tamponade is a rare but serious emergency condition in the pediatric population. As treatment, a pericardial drain is often placed to evacuate the fluid. We present a case of a 4-year-old girl with cardiac tamponade secondary to renal failure. After the tamponade resolved, she suffered cardiovascular collapse upon attempted drain withdrawal. This case highlights an unusual cause for cardiovascular collapse, which occurred on blind removal of a pericardial drain. PMID:27625522

  5. Pre-Treatment with Allopurinol or Uricase Attenuates Barrier Dysfunction but Not Inflammation during Murine Ventilator-Induced Lung Injury

    PubMed Central

    Kuipers, Maria T.; Aslami, Hamid; Vlaar, Alexander P. J.; Juffermans, Nicole P.; Tuip-de Boer, Anita M.; Hegeman, Maria A.; Jongsma, Geartsje; Roelofs, Joris J. T. H.; van der Poll, Tom; Schultz, Marcus J.; Wieland, Catharina W.

    2012-01-01

    Introduction Uric acid released from injured tissue is considered a major endogenous danger signal and local instillation of uric acid crystals induces acute lung inflammation via activation of the NLRP3 inflammasome. Ventilator-induced lung injury (VILI) is mediated by the NLRP3 inflammasome and increased uric acid levels in lung lavage fluid are reported. We studied levels in human lung injury and the contribution of uric acid in experimental VILI. Methods Uric acid levels in lung lavage fluid of patients with acute lung injury (ALI) were determined. In a different cohort of cardiac surgery patients, uric acid levels were correlated with pulmonary leakage index. In a mouse model of VILI the effect of allopurinol (inhibits uric acid synthesis) and uricase (degrades uric acid) pre-treatment on neutrophil influx, up-regulation of adhesion molecules, pulmonary and systemic cytokine levels, lung pathology, and regulation of receptors involved in the recognition of uric acid was studied. In addition, total protein and immunoglobulin M in lung lavage fluid and pulmonary wet/dry ratios were measured as markers of alveolar barrier dysfunction. Results Uric acid levels increased in ALI patients. In cardiac surgery patients, elevated levels correlated significantly with the pulmonary leakage index. Allopurinol or uricase treatment did not reduce ventilator-induced inflammation, IκB-α degradation, or up-regulation of NLRP3, Toll-like receptor 2, and Toll-like receptor 4 gene expression in mice. Alveolar barrier dysfunction was attenuated which was most pronounced in mice pre-treated with allopurinol: both treatment strategies reduced wet/dry ratio, allopurinol also lowered total protein and immunoglobulin M levels. Conclusions Local uric acid levels increase in patients with ALI. In mice, allopurinol and uricase attenuate ventilator-induced alveolar barrier dysfunction. PMID:23226314

  6. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder. PMID:26498253

  7. EFFECTS OF NUCLEAR INDUCED BREAKUP ON THE FUSION OF 6Li+12C AND 6He+12C SYSTEMS AROUND BARRIER ENERGIES

    NASA Astrophysics Data System (ADS)

    Duhan, Sukhvinder S.; Singh, Manjeet; Kharab, Rajesh

    2012-06-01

    We have studied the effects of nuclear induced breakup channel coupling on the fusion cross-section for 6Li+12C and 6He+12C systems in the near barrier energy regime using the dynamic polarization potential (DPP) approach. It has been found that there is enhancement in the fusion cross-section with respect to standard one-dimensional barrier penetration model in the below barrier energy regime while at energies above the barrier there is suppression of fusion cross-section with respect to simple barrier penetration model is observed. The agreement between data and predictions for 6Li+12C system improves significantly as a result of the inclusion of nuclear induced DPP.

  8. Unsaturated zone moisture and vapor movement induced by temperature variations in asphalt barrier field lysimeters

    SciTech Connect

    Holford, D.J.; Fayer, M.J.

    1990-08-01

    Protective barriers are being considered for use at the Hanford Site to enhance the isolation of radioactive wastes from water, plant, and animal intrusion. Lysimeters were constructed to evaluate the performance of asphalt barrier formulations under natural environmental conditions. These lysimeters were constructed of 1.7-m lengths of PVC pipe that have a diameter of 30 cm. The lysimeters were filled with layers of gravel, coarse sand, and asphalt. The sand and gravel placed under the asphalt barrier were wet when installed. TOUGH was used to conduct simulations to assess the effect of temperature variations on moisture and vapor movement beneath the asphalt layer in field test lysimeters. All variables in TOUGH were converted to double precision so that simulations could be run on a Sun-4 UNIX workstation. A radially symmetric grid was used to simulate the lysimeter. 8 refs., 9 figs.

  9. Confinement of electromigration induced void propagation in Cu interconnect by a buried Ta diffusion barrier layer

    NASA Astrophysics Data System (ADS)

    Yan, M. Y.; Tu, K. N.; Vairagar, A. V.; Mhaisalkar, S. G.; Krishnamoorthy, Ahila

    2005-12-01

    Direct observation, by means of in situ scanning electron microscopy, of void heterogeneous nucleation and migration controlled electromigration failure mechanism in Cu dual damascene interconnect structures has been recently reported [A. V. Vairagar, S. G. Mhaisalkar, A. Krishnamoorthy, K. N. Tu, A. M. Gusak, M. A. Meyer, and E. Zschech, Appl. Phys. Lett. 85, 2502 (2004)] In the present study, a dual damascene structure with an additional 25nm Ta diffusion barrier embedded into the upper Cu layer was fabricated. This thin layer of diffusion barrier blocked voids from propagating into the via, thus eliminating the previously reported failure mechanism. With this structure, a lifetime improvement of at least 40 times was achieved. Analysis on failed samples suggested that failures in samples with the embedded Ta barrier layer occurred at the bottom of the via, which were caused by void migration along the bottom of the Cu lines.

  10. Statins Inhibit Fibrillary β-Amyloid Induced Inflammation in a Model of the Human Blood Brain Barrier

    PubMed Central

    Griffin, Jarred M.; Kho, Dan; Graham, E. Scott; Nicholson, Louise F. B.; O’Carroll, Simon J.

    2016-01-01

    Background Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer’s disease (AD) pathology. The amyloid beta (Aβ) protein is known to exist in several forms and is a key modulator of AD that is known to cause inflammation and changes to BBB function. While one of these forms, fibrillary Aβ (fAβ), is known to cause endothelial cell death at the BBB, no studies have looked specifically at its role on inflammation in a model of the human BBB. Aims To determine if fAβ is inflammatory to the human BBB. As statins have been shown to be anti-inflammatory and protective in AD, we also tested if these could inhibit the inflammatory effect of fAβ. Methods Using cultured cerebral endothelial cells and astrocytes we determined changes in cytokine release, cell toxicity and barrier function in response to fibrillary β-amyloid1–42 (fAβ1–42) alone and in combination with statins. Results fAβ1–42 induced inflammatory cytokine release from endothelial cells in the absence of cell toxicity. It also induced astrocyte cytokine release and cell death and caused a loss of barrier integrity. Statin treatment inhibited all of these effects. Conclusions We conclude that fAβ1–42 has both inflammatory and cytotoxic effects on the BBB and the protective effect of statins in AD may in part be through inhibiting these effects. PMID:27309956

  11. Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells

    NASA Astrophysics Data System (ADS)

    Kaushik, Nagendra K.; Uhm, Hansup; Ha Choi, Eun

    2012-02-01

    Induction of micronucleus formation (cytogenetic damage) in brain cancer cells upon exposure of dielectric barrier discharge plasma has been investigated. We have investigated the influence of exposure and incubation times on T98G brain cancer cells by using growth kinetic, clonogenic, and micronucleus formation assay. We found that micronucleus formation rate directly depends on the plasma exposure time. It is also shown that colony formation capacity of cells has been inhibited by the treatment of plasma at all doses. Cell death and micronucleus formation are shown to be significantly elevated by 120 and 240 s exposure of dielectric barrier discharge plasma.

  12. Non-sting barrier cream in radiotherapy-induced skin reactions.

    PubMed

    Scott, Audrey

    A pilot evaluation was undertaken in 13 patients with head and neck cancer exploring the use of a non-sting barrier film (Sorbaderm(®,) Aspen Medical Europe Ltd). The Society of Radiographers issued guidance in 2013 warning their members that the use of Aqueous cream for moisturising the skin during radiotherapy was potentially harmful. Patients were monitored over a period of 6 weeks and the aim was to explore whether applying non-sting barrier cream provided a protective barrier that did not impair treatment, slowed or prevented skin damage, was easy and simple to apply for patients and carers, improved quality of life for patients during radiotherapy or aided healing. There appeared to be a delay in skin breakdown in this evaluation from week 3 to week 4 and then only mild pain was recorded and with a maximum Radiation Therapy Oncology Group scale of 2.5 in the patient that had combined chemotherapy and radiotherapy. The patients' overall assessment demonstrated that the use of non-sting barrier cream provided symptom relief in both dry, tightening and itching of the skin associated with radiotherapy. All except one patient found the cream easy to apply. The head and neck nursing team rated the product as 'good' to 'very good'. PMID:26018180

  13. Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability.

    PubMed

    Mooney, Skyler J; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo

    2016-01-01

    Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier. PMID:27459643

  14. Injection barrier induced deviations in space charge limited conduction in doped poly(3-methylthiophene) based devices

    NASA Astrophysics Data System (ADS)

    Khan, Motiur Rahman; Varade, Vaibhav; Koteswara Rao, K. S. R.; Menon, R.

    2015-10-01

    The carrier density dependent current-voltage (J - V) characteristics of electrochemically prepared poly(3-methylthiophene) (P3MeT) have been investigated in Pt/P3MeT/Al devices, as a function of temperature from 280 to 84 K. In these devices, the charge transport is found to be mainly governed by different transport regimes of space charge limited conduction (SCLC). In a lightly doped device, SCLC controlled by exponentially distributed traps ( V l + 1 law, l > 1) is observed in the intermediate voltage range (0.5-2 V) at all temperatures. However, at higher bias (>2 V), the current deviates from the usual V l + 1 law where the slope is found to be less than 2 of the logJ-logV plot, which is attributed to the presence of the injection barrier. These deviations gradually disappear at higher doping level due to reduction in the injection barrier. Numerical simulations of the V l + 1 law by introducing the injection barrier show good agreement with experimental data. The results show that carrier density can tune the charge transport mechanism in Pt/P3MeT/Al devices to understand the non-Ohmic behavior. The plausible reasons for the origin of injection barrier and the transitions in the transport mechanism with carrier density are discussed.

  15. Focused Ultrasound-Induced Neurogenesis Requires an Increase in Blood-Brain Barrier Permeability

    PubMed Central

    Mooney, Skyler J.; Shah, Kairavi; Yeung, Sharon; Burgess, Alison; Aubert, Isabelle; Hynynen, Kullervo

    2016-01-01

    Transcranial focused ultrasound technology used to transiently open the blood-brain barrier, is capable of stimulating hippocampal neurogenesis; however, it is not yet known what aspects of the treatment are necessary for enhanced neurogenesis to occur. The present study set out to determine whether the opening of blood-brain barrier, the specific pressure amplitudes of focused ultrasound, and/or the intravenous administration of microbubbles (phospholipid microspheres) are necessary for the enhancement of neurogenesis. Specifically, mice were exposed to burst (10ms, 1Hz burst repetition frequency) focused ultrasound at the frequency of 1.68MHz and with 0.39, 0.78, 1.56 and 3.0MPa pressure amplitudes. These treatments were also conducted with or without microbubbles, at 0.39 + 0.78MPa or 1.56 + 3.0MPa, respectively. Only focused ultrasound at the ~0.78 MPa pressure amplitude with microbubbles promoted hippocampal neurogenesis and was associated with an increase in blood-brain barrier permeability. These results suggest that focused ultrasound -mediated neurogenesis is dependent upon the opening of the blood-brain barrier. PMID:27459643

  16. Protective effect of 1,25-dihydroxyvitamin D3 on ethanol-induced intestinal barrier injury both in vitro and in vivo.

    PubMed

    Chen, Shan-Wen; Ma, Yuan-Yuan; Zhu, Jing; Zuo, Shuai; Zhang, Jun-Ling; Chen, Zi-Yi; Chen, Guo-Wei; Wang, Xin; Pan, Yi-Sheng; Liu, Yu-Cun; Wang, Peng-Yuan

    2015-09-01

    Studies have suggested the role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in protecting intestinal barrier function from injuries induced by multiple reagents. Vitamin D deficiency was reported to be associated with poor prognosis in patients with alcoholic liver disease (ALD). This study is designed to investigate the effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier dysfunction and the underlying mechanisms utilizing Caco-2 cell monolayers and a mouse model with acute ethanol injury. In Caco-2 monolayers, ethanol significantly increased monolayer permeability, disrupted TJ distribution, increased phosphorylation level of MLC, and induced generation of ROS compared with controls. However, pre-treatment with 1,25(OH)2D3 greatly ameliorated the ethanol-induced barrier dysfunction, TJ disruption, phosphorylation level of MLC, and generation of ROS compared with ethanol-exposed monolayers. Mice fed with vitamin d-sufficient diet had a higher plasma level of 25(OH)D3 and were more resistant to ethanol-induced acute intestinal barrier injury compared with the vitamin d-deficient group. These results suggest that the suppression of generation of ROS and increased phosphorylation level of MLC might be one of the mechanisms underlying the protective effect of 1,25(OH)2D3 on ethanol-induced intestinal barrier injury and provide evidence for the application of vitamin D as therapeutic factors against ethanol-induced gut leakiness. PMID:26068064

  17. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    PubMed

    Zhang, Xun E; Adderley, Shaquria P; Breslin, Jerome W

    2016-01-01

    Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process. PMID:27187066

  18. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement

    PubMed Central

    Zhang, Xun E.; Adderley, Shaquria P.

    2016-01-01

    Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process. PMID:27187066

  19. Electron-Beam-Induced Deposition as a Technique for Analysis of Precursor Molecule Diffusion Barriers and Prefactors.

    PubMed

    Cullen, Jared; Lobo, Charlene J; Ford, Michael J; Toth, Milos

    2015-09-30

    Electron-beam-induced deposition (EBID) is a direct-write chemical vapor deposition technique in which an electron beam is used for precursor dissociation. Here we show that Arrhenius analysis of the deposition rates of nanostructures grown by EBID can be used to deduce the diffusion energies and corresponding preexponential factors of EBID precursor molecules. We explain the limitations of this approach, define growth conditions needed to minimize errors, and explain why the errors increase systematically as EBID parameters diverge from ideal growth conditions. Under suitable deposition conditions, EBID can be used as a localized technique for analysis of adsorption barriers and prefactors. PMID:26340502

  20. Effect of a two-dimensional potential on the rate of thermally induced escape over the potential barrier

    SciTech Connect

    Han, S.; Lapointe, J.; Lukens, J.E. )

    1992-09-01

    The thermally induced escape rate of a particle trapped in a two-dimensional (2D) potential well has been investigated through experiment and numerical simulations. The measurements were performed on a special type of superconducting quantum interference device (SQUID) which has 2 degrees of freedom. The energies associated with the motion perpendicular to (transverse) and along (longitudinal) the escape direction are quite different: the ratio between the transverse and longitudinal small oscillation frequencies is {omega}{sub {ital t}}/{omega}{sub {ital l}}{similar to}7. The SQUID's parameters, which were used to determine the potential shape and energy scales were all independently determined. All data were obtained under conditions for which the 2D thermal activation (TA) model is expected to be valid. The results were found in good agreement with the theoretical prediction. The measured thermal activation energy is found to be the same as the barrier height calculated from the independently determined potential parameters. No evidence of apparent potential barrier enhancement recently reported in a similar system was found. In addition, the results of our numerical simulations suggest that the region in which the 2D thermal activation model is applicable may be extended to barriers as low as {Delta}{ital U}{similar to}{ital k}{sub {ital B}T}.

  1. Magnetic field induced suppression of the forward bias current in Bi2Se3/Si Schottky barrier diodes

    NASA Astrophysics Data System (ADS)

    Jin, Haoming; Hebard, Arthur

    Schottky diodes formed by van der Waals bonding between freshly cleaved flakes of the topological insulator Bi2Se3 and doped silicon substrates show electrical characteristics in good agreement with thermionic emission theory. The motivation is to use magnetic fields to modulate the conductance of the topologically protected conducting surface state. This surface state in close proximity to the semiconductor surface may play an important role in determining the nature of the Schottky barrier. Current-voltage (I-V) and capacitance-voltage (C-V) characteristics were obtained for temperatures in the range 50-300 K and magnetic fields, both perpendicular and parallel to the interface, as high as 7 T. The I-V curve shows more than 6 decades linearity on semi-logarithmic plots, allowing extraction of parameters such as ideality (η), zero-voltage Schottky barrier height (SBH), and series resistance (Rs). In forward bias we observe a field-induced decrease in current which becomes increasingly more pronounced at higher voltages and lower temperature, and is found to be correlated with changes in Rs rather than other barrier parameters. A comparison of changes in Rs in both field direction will be made with magnetoresistance in Bi2Se3 transport measurement. The work is supported by NSF through DMR 1305783.

  2. Schottky-Barrier-Induced AC Surface Photovoltages in Au-Precipitated n-Type Si(001) Surfaces

    NASA Astrophysics Data System (ADS)

    Shimizu, Hirofumi; Sanada, Yuji

    2011-08-01

    We have studied the behavior of Au clusters on the top surface of a SiO2 film and/or at the SiO2/Si interface as a function of oxidation temperature between room temperature (RT) and 500 °C in conjunction with a Schottky-barrier-induced AC surface photovoltage (SPV) and an enhanced SiO2 growth due to Au at 500 °C. Upon rinsing an n-type Si(001) wafer in a Au-contaminated aqueous solution, precipitated Au atoms are observed as clusterlike Au granules on the top surface of SiO2 (Au surface concentration, 2.3 ×1015 atoms/cm2). In thermally oxidized Au-contaminated n-type Si(001) wafers between 100 and 500 °C, a Au cluster of a similar shape is also observed. Chemical analysis gives evidence that Au existed at the SiO2/Si interface, which produced Au/n-Si Schottky-barrier-type AC SPV between 100 and 500 °C as well as at both RT and higher temperatures, indicating that the Au/n-Si Schottky barrier remains in a similar manner. In the Au-contaminated n-Si thermally oxidized at 500 °C, the catalytic action of Au atoms enhances SiO2 growth as well as the case at high temperatures between 750 and 900 °C. The mechanism of the enhanced growth is proposed.

  3. The alkaline pH-adapted skin barrier is disrupted severely by SLS-induced irritation.

    PubMed

    Kim, E; Kim, S; Nam, G W; Lee, H; Moon, S; Chang, I

    2009-08-01

    The pH of the healthy skin is 5.5 and maintained by many regulatory mechanisms. The pH of the skin care product we use on a daily basis can have an influence on the skin properties. To investigate how the physical properties of skin change after the alkaline or acidic pH of the skin care products are applied on the skin for a long term, we adjusted the pH of the skin care products to 3, 5 and 8 (A, B, C), with glycolic acid and triethanolamine. For 5 weeks the skin care products were applied on 20 healthy subjects' ventral forearm and the skin physical properties were measured. After 5 weeks, skin responses to the external stress of 1% (w/v) SLS (sodium lauryl sulphate) irritation and erythema by UV were measured. Skin colour and skin UV response were not altered by the pH. However, on the C-applied site (pH 8) the transepidermal water loss of stratum corneum (SC) increased significantly, the water content increased and desquamation decreased, respectively, and the SLS significantly impaired the skin barrier in comparison with other sites. The alkaline skin care product impaired the skin barrier after repeated application over 5-week period and the skin barrier was disrupted severely by 1% SLS exposure because SC was already impaired by alkaline pH and sensitive to external stress. This suggests that the pH of daily skin care products is very important for skin barrier homeostasis. PMID:19467032

  4. Spin orbit splitting of the photon induced Fano resonance in an oscillating graphene electrostatic barrier

    SciTech Connect

    Biswas, R.; Sinha, C.

    2014-04-07

    We investigate theoretically the effect of a time dependent oscillating potential on the transport property of the Dirac Fermion through a monolayer graphene electrostatic barrier under the influence of the Rashba spin orbit interaction. The time dependent problem is solved in the frame work of the non-perturbative Floquet approach. It is noted that the dynamic condition of the barrier may be controlled by tuning the Rashba parameter. Introduction of the spin orbit interaction causes splitting of the Fano resonance (FR), a characteristic feature in photon assisted tunneling. The separation between the spin split FR's gives an indirect measure of the fine structure of the quasi-hole bound state inside the barrier. The present findings on the Rashba splitting of the FR and its external control by tuning the oscillating field parameters might have potential for applications in spintronic devices, especially in the spin field effect transistors. The spin polarization of different Floquet sidebands is found to be quite sensitive to the spin-pseudospin interaction.

  5. Dexamethasone Attenuates VEGF Expression and Inflammation but Not Barrier Dysfunction in a Murine Model of Ventilator–Induced Lung Injury

    PubMed Central

    Hegeman, Maria A.; Hennus, Marije P.; Cobelens, Pieter M.; Kavelaars, Annemieke; Jansen, Nicolaas J. G.; Schultz, Marcus J.; van Vught, Adrianus J.; Heijnen, Cobi J.

    2013-01-01

    Background Ventilator–induced lung injury (VILI) is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF) has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar–capillary barrier dysfunction in an established murine model of VILI. Methods Healthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O (“lower” tidal volumes of ∼7.5 ml/kg; LVT) or 18 cmH2O (“higher” tidal volumes of ∼15 ml/kg; HVT). Dexamethasone was intravenously administered at the initiation of HVT–ventilation. Non–ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios. Results Particularly HVT–ventilation led to alveolar–capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro–inflammatory response in lungs of HVT–ventilated mice, without improving alveolar–capillary permeability, gas exchange and pulmonary edema formation. Conclusions Dexamethasone treatment completely abolishes ventilator–induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar–capillary barrier dysfunction in an established murine model of VILI. PMID:23451215

  6. Protective Effects of Ferulic Acid against Heat Stress-Induced Intestinal Epithelial Barrier Dysfunction In Vitro and In Vivo

    PubMed Central

    He, Shasha; Liu, Fenghua; Xu, Lei; Yin, Peng; Li, Deyin; Mei, Chen; Jiang, Linshu; Ma, Yunfei; Xu, Jianqin

    2016-01-01

    Heat stress is important in the pathogenesis of intestinal epithelial barrier dysfunction. Ferulic acid (FA), a phenolic acid widely found in fruits and vegetables, can scavenge free radicals and activate cell stress responses. This study is aimed at investigating protective effects of FA on heat stress-induced dysfunction of the intestinal epithelial barrier in vitro and in vivo. Intestinal epithelial (IEC-6) cells were pretreated with FA for 4 h and then exposed to heat stress. Heat stress caused decreased transepithelial electrical resistance (TER) and increased permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4). Both effects were inhibited by FA in a dose-dependent manner. FA significantly attenuated the decrease in occludin, ZO-1 and E-cadherin expression observed with heat stress. The distortion and redistribution of occludin, ZO-1 and E-cadherin proteins were also effectively prevented by FA pretreatment. Moreover, heat stress diminished electron-dense material detected in tight junctions (TJs), an effect also alleviated by FA in a dose-dependent manner. In an in vivo heat stress model, FA (50 mg/kg) was administered to male Sprague–Dawley rats for 7 consecutive days prior to exposure to heat stress. FA pretreatment significantly attenuated the effects of heat stress on the small intestine, including the increased FD4 permeability, disrupted tight junctions and microvilli structure, and reduced occludin, ZO-1 and E-cadherin expression. Taken together, our results demonstrate that FA pretreatment is potentially protective against heat stress-induced intestinal epithelial barrier dysfunction. PMID:26894689

  7. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress.

    PubMed

    Tong, Ling-Chang; Wang, Yue; Wang, Zhi-Bin; Liu, Wei-Ye; Sun, Sheng; Li, Ling; Su, Ding-Feng; Zhang, Li-Chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7-14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  8. Protective Effects of Ferulic Acid against Heat Stress-Induced Intestinal Epithelial Barrier Dysfunction In Vitro and In Vivo.

    PubMed

    He, Shasha; Liu, Fenghua; Xu, Lei; Yin, Peng; Li, Deyin; Mei, Chen; Jiang, Linshu; Ma, Yunfei; Xu, Jianqin

    2016-01-01

    Heat stress is important in the pathogenesis of intestinal epithelial barrier dysfunction. Ferulic acid (FA), a phenolic acid widely found in fruits and vegetables, can scavenge free radicals and activate cell stress responses. This study is aimed at investigating protective effects of FA on heat stress-induced dysfunction of the intestinal epithelial barrier in vitro and in vivo. Intestinal epithelial (IEC-6) cells were pretreated with FA for 4 h and then exposed to heat stress. Heat stress caused decreased transepithelial electrical resistance (TER) and increased permeability to 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4). Both effects were inhibited by FA in a dose-dependent manner. FA significantly attenuated the decrease in occludin, ZO-1 and E-cadherin expression observed with heat stress. The distortion and redistribution of occludin, ZO-1 and E-cadherin proteins were also effectively prevented by FA pretreatment. Moreover, heat stress diminished electron-dense material detected in tight junctions (TJs), an effect also alleviated by FA in a dose-dependent manner. In an in vivo heat stress model, FA (50 mg/kg) was administered to male Sprague-Dawley rats for 7 consecutive days prior to exposure to heat stress. FA pretreatment significantly attenuated the effects of heat stress on the small intestine, including the increased FD4 permeability, disrupted tight junctions and microvilli structure, and reduced occludin, ZO-1 and E-cadherin expression. Taken together, our results demonstrate that FA pretreatment is potentially protective against heat stress-induced intestinal epithelial barrier dysfunction. PMID:26894689

  9. Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress

    PubMed Central

    Tong, Ling-chang; Wang, Yue; Wang, Zhi-bin; Liu, Wei-ye; Sun, Sheng; Li, Ling; Su, Ding-feng; Zhang, Li-chao

    2016-01-01

    Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7–14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway. PMID:27574508

  10. Expression of Aquaporin 4 and Breakdown of the Blood-Brain Barrier after Hypoglycemia-Induced Brain Edema in Rats

    PubMed Central

    Deng, Jiangshan; Zhao, Fei; Yu, Xiaoyan; Zhao, Yuwu; Li, Dawei; Shi, Hong; Sun, Yongning

    2014-01-01

    Background Hypoglycemia-induced brain edema is a severe clinical event that often results in death. The mechanisms by which hypoglycemia induces brain edema are unclear. Methods In a hypoglycemic injury model established in adult rats, brain edema was verified by measuring brain water content and visualizing water accumulation using hematoxylin and eosin staining. Temporal expression of aquaporin 4 (AQP4) and the integrity of the blood-brain barrier (BBB) were evaluated. We assessed the distribution and expression of AQP4 following glucose deprivation in astrocyte cultures. Results Brain edema was induced immediately after severe hypoglycemia but continued to progress even after recovery from hypoglycemia. Upregulation of AQP4 expression and moderate breakdown of the BBB were observed 24 h after recovery. In vitro, significant redistribution of AQP4 to the plasma membrane was induced following 6 h glucose deprivation. Conclusion Hypoglycemia-induced brain edema is caused by cytotoxic and vasogenic factors. Changes in AQP4 location and expression may play a protective role in edema resolution. PMID:25264602

  11. 14 CFR 29.1021 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil system drains. 29.1021 Section 29.1021... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be...

  12. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and...

  13. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and...

  14. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Oil system drains. 25.1021 Section 25.1021... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be...

  15. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil system drains. 25.1021 Section 25.1021... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be...

  16. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Oil system drains. 25.1021 Section 25.1021... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be...

  17. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and...

  18. 14 CFR 25.1021 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil system drains. 25.1021 Section 25.1021... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant Oil System § 25.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be...

  19. 14 CFR 29.1021 - Oil system drains.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Oil system drains. 29.1021 Section 29.1021... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be...

  20. 14 CFR 29.1021 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil system drains. 29.1021 Section 29.1021... STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Oil System § 29.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be...

  1. 14 CFR 27.1021 - Oil system drains.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Oil system drains. 27.1021 Section 27.1021... STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Oil System § 27.1021 Oil system drains. A drain (or drains) must be provided to allow safe drainage of the oil system. Each drain must— (a) Be accessible; and...

  2. Valproic Acid Treatment Inhibits Hypoxia-Inducible Factor 1α Accumulation and Protects against Burn-Induced Gut Barrier Dysfunction in a Rodent Model

    PubMed Central

    Luo, Hong-Min; Du, Ming-Hua; Lin, Zhi-Long; Zhang, Lin; Ma, Li; Wang, Huan; Yu, Wen; Lv, Yi; Lu, Jiang-Yang; Pi, Yu-Li; Hu, Sen; Sheng, Zhi-Yong

    2013-01-01

    Objective Burn-induced gut dysfunction plays an important role in the development of sepsis and multiple organ dysfunction. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) is critical in paracelluar barrier functions via regulating vascular endothelial growth factor (VEGF) and myosin light chain kinase (MLCK) expression. Previous studies have also demonstrated that histone deacetylase inhibitors (HDACIs) can repress HIF-1α. This study aims to examine whether valproic acid (VPA), a HDACI, protects against burn-induced gut barrier dysfunction via repressing HIF-1α-dependent upregulation of VEGF and MLCK expression. Methods Rats were subjected to third degree 55% TBSA burns and treated with/ without VPA (300mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and histologic evaluation. Histone acetylation, tight junction protein zonula occludens 1 (ZO-1), VEGF, MLCK and HIF-1α were measured. In addition, CaCO2 cells were transfected with siRNA directed against HIF-1α and were stimulated with CoCl2 (1mM) for 24 hours with/without VPA (2mM) followed by analysis of HIF-1α, MLCK, VEGF and ZO-1. Results Burn insults resulted in a significant increase in intestinal permeability and mucosal damage, accompanied by a significant reduction in histone acetylation, ZO-1, upregulation of VEGF, MLCK expression, and an increase in HIF-1α accumulation. VPA significantly attenuated the increase in intestinal permeability, mucosa damage, histone deacetylation and changes in ZO-1 expression. VPA also attenuated the increased VEGF, MLCK and HIF-1α protein levels. VPA reduced HIF-1α, MLCK and VEGF production and prevented ZO-1 loss in CoCl2-stimulated Caco-2 cells. Moreover, transfection of siRNA directed against HIF-1α led to inhibition of MLCK and VEGF production, accompanied by upregulation of ZO-1. Conclusions These results indicate that VPA can protect against burn-induced

  3. Partial Enteral Nutrition Mitigated Ischemia/Reperfusion-Induced Damage of Rat Small Intestinal Barrier

    PubMed Central

    Wu, Chao; Wang, Xinying; Jiang, Tingting; Li, Chaojun; Zhang, Li; Gao, Xuejin; Tian, Feng; Li, Ning; Li, Jieshou

    2016-01-01

    Background and Aims: This study was designed to investigate a relatively optimum dose of partial enteral nutrition (PEN) which effectively attenuates intestinal barrier dysfunction initiated by ischemia/reperfusion injury (IRI). Methods: In experiment 1, 60 male Sprague-Dawley (SD) rats were subjected to intestinal IRI and assigned to six groups according to the different proportion of EN administrations: namely total parenteral nutrition (TPN or 0%EN), 10%EN, 20%EN, 40%EN, 60%EN, and total enteral nutrition (TEN or 100%) groups, the deficits of intraluminal calorie were supplemented by PN. In experiment 2, 50 male SD rats were subjected to intestinal IRI and divided into five groups based on the results of experiment 1: TPN, TEN, 20%EN, TPN plus pretreatment with NF-κB antagonist 30 min before IRI (TPN+PDTC), and TPN plus pretreatment with HIF-1α antagonist 30 min before IRI (TPN+YC-1) groups. Results: In experiment 1, previous IRI combined with subsequent EN shortage disrupted the structure of intestinal epithelial cell and tight junctions (TJs). While 20% dose of EN had an obviously protective effect on these detrimental consequences. In experiment 2, compared with TPN only, 20%EN exerted a significant protection of barrier function of intestinal epithelium. Analogous results were observed when TPN combined with specific NF-κB/HIF-1α inhibitors (PDTC and YC-1). Meanwhile, the expression of NF-κB/HIF-1α had a similar trend among the groups. Conclusions: Our findings indicate that 20%EN is the minimally effective dosage of EN which promotes the recovery of intestinal barrier function after IRI in a rat model. Furthermore, we discreetly speculate that this benefit is, at least partly, related to NF-κB/HIF-1α pathway expression. PMID:27548209

  4. Analysis of {alpha}-induced reactions on {sup 151}Eu below the Coulomb barrier

    SciTech Connect

    Avrigeanu, V.; Avrigeanu, M.

    2011-01-15

    Novel measurements of ({alpha},{gamma}) and ({alpha},n) reaction cross sections on the target nucleus {sup 151}Eu, close to the reaction thresholds, support the choice of recently proposed parameters of the {alpha}-particle optical model potential below the Coulomb barrier. A better understanding of the {alpha}-particle optical potential at these energies leads to a statistical model analysis of additional partial cross sections that were measured but not considered within a former model analysis. On this basis we have tentatively assigned a modified J{sup {pi}}=9{sup -} spin and parity to the 22.7-h isomer in {sup 154}Tb.

  5. Differential glucocorticoid-induced closure of the blood-milk barrier during lipopolysaccharide- and lipoteichoic acid-induced mastitis in dairy cows.

    PubMed

    Wall, Samantha K; Hernández-Castellano, Lorenzo E; Ahmadpour, Amir; Bruckmaier, Rupert M; Wellnitz, Olga

    2016-09-01

    Bacteria invading the mammary gland can cause pathogen-dependent differences in the permeability of the blood-milk barrier leading to the differential paracellular transfer of blood and milk components. Glucocorticoids such as prednisolone (PRED) are known to increase the integrity of the blood-milk barrier and quickly restore the decreased milk quality associated with mastitis. The objective of this study was to examine the effect of intramammary PRED on the differential permeability of the blood-milk barrier during mastitis induced by lipopolysaccharide (LPS) from Escherichia coli or lipoteichoic acid (LTA) from Staphylococcus aureus. Thirty-one dairy cows, divided into 6 groups, were injected via a teat canal with LPS, LTA, LPS and PRED, LTA and PRED, saline (control), or PRED. Milk and blood samples were collected 0 to 8h after challenge and analyzed for somatic cell count, IgG, serum albumin, and lactate dehydrogenase in milk, or α-lactalbumin in plasma. Somatic cell count was similarly elevated in LPS- and LTA-challenged quarters and was reduced to control quarter levels only in LTA-challenged quarters with PRED administration. Lactate dehydrogenase activity was highly elevated in LPS quarters and only slightly elevated in LTA quarters, but decreased to control quarter levels with PRED administration. For serum albumin and IgG, only LPS quarters showed an elevation in concentration and PRED treatment reduced the concentration to control quarter level. We found no differences in α-lactalbumin concentrations in plasma in PRED-treated cows compared with cows that only received LPS or LTA. In conclusion, the pathogen-specific appearance of blood constituents in milk during mastitis demonstrates a differential activation of the blood-milk barrier that, in turn, can be manipulated by intramammary glucocorticoids. The results show that the administration of PRED during mastitis increases the blood-milk barrier integrity but has implications in reducing the

  6. Contrast-Enhanced Ultrasound Imaging for the Detection of Focused Ultrasound-Induced Blood-Brain Barrier Opening

    PubMed Central

    Fan, Ching-Hsiang; Lin, Wun-Hao; Ting, Chien-Yu; Chai, Wen-Yen; Yen, Tzu-Chen; Liu, Hao-Li; Yeh, Chih-Kuang

    2014-01-01

    The blood-brain barrier (BBB) can be transiently and locally opened by focused ultrasound (FUS) in the presence of microbubbles (MBs). Various imaging modalities and contrast agents have been used to monitor this process. Unfortunately, direct ultrasound imaging of BBB opening with MBs as contrast agent is not feasible, due to the inability of MBs to penetrate brain parenchyma. However, FUS-induced BBB opening is accompanied by changes in blood flow and perfusion, suggesting the possibility of perfusion-based ultrasound imaging. Here we evaluated the use of MB destruction-replenishment, which was originally developed for analysis of ultrasound perfusion kinetics, for verifying and quantifying FUS-induced BBB opening. MBs were intravenously injected and the BBB was disrupted by 2 MHz FUS with burst-tone exposure at 0.5-0.7 MPa. A perfusion kinetic map was estimated by MB destruction-replenishment time-intensity curve analysis. Our results showed that the scale and distribution of FUS-induced BBB opening could be determined at high resolution by ultrasound perfusion kinetic analysis. The accuracy and sensitivity of this approach was validated by dynamic contrast-enhanced MRI. Our successful demonstration of ultrasound imaging to monitor FUS-induced BBB opening provides a new approach to assess FUS-dependent brain drug delivery, with the benefit of high temporal resolution and convenient integration with the FUS device. PMID:25161701

  7. Improving thrust by pulse-induced breakdown enhancement in AC surface dielectric barrier discharge actuators for airflow control

    NASA Astrophysics Data System (ADS)

    Yan, Huijie; Yang, Liang; Qi, Xiaohua; Ren, Chunsheng

    2016-07-01

    The characteristics of a plate-to-plate AC surface dielectric barrier discharge (SDBD) actuator using the pulse-induced breakdown enhancing method are experimentally investigated. The encapsulated electrode is supplied with a sine high AC voltage, while the exposed electrode is feed by a synchronized pulse voltage. Based on the thrust force and power consumption measurements, a parametric study was performed using a positive pulse applied at the trough phase of the AC cycles in which the thrust force was observed to increase by about 100% to 300% and the efficiency up to about 100% compared with the AC-only supply conditions for different AC voltages within the tested range. The pulse-induced breakdown effect was analyzed from the electrical and light emission waveforms to reveal the underlying mechanism. The surface potential due to the charge deposition effect was also measured using a specially designed corona-like discharge potential probe. It is shown that the pulse-induced breakdown was able to cause a temporarily intensified local electric field to enhance the glow-like discharge and meanwhile increase the time-average surface potential in the region further downstream. The improvement in the force by the enhancement in the pulse-induced breakdown was mainly due to enhancements in the glow-like discharge and the surface potential increment, with the latter being more important when the AC voltage is higher.

  8. Urokinase-Treated Antithrombogenic Drains and Optimized Drain Placement in Endoscopic Lumbar Decompressive Surgery.

    PubMed

    Nakamura, Shu; Ikeda, Shoji; Taguchi, Mitsuto

    2016-07-01

    Background Spinal epidural hematoma (SEH) frequently occurs after microendoscopic decompressive laminotomy (MEDL), and a drain may not be functioning sufficiently. Objective To reduce the incidence of SEH after MEDL. Methods  A urokinase-treated antithrombogenic drain, which is available only with a large diameter, was reduced in diameter and used after MEDL. Magnetic resonance imaging (MRI) and computed tomography (CT) were performed 36 to 48 hours after surgery. The size of the SEH was measured by MRI, and the location of the drain tip was assessed by CT scan. After imaging, the drain was removed. Results Use of the urokinase-treated antithrombogenic drain reduced the incidence of SEH. However, the drain was not adequately placed in many cases, limiting the effect of the drainage. When the urokinase-treated antithrombogenic drain was placed contralaterally to the approach side using an unsheathed endoscope, the incidence of SEH was further reduced. Conclusions The urokinase-treated antithrombogenic drain prevented thrombus-related drain obstruction. In addition, unsheathed endoscopic contralateral placement of the drain was effective for SEH prevention. PMID:26935298

  9. Might digital drains speed up the time to thoracic drain removal?

    PubMed

    Afoke, Jonathan; Tan, Carol; Hunt, Ian; Zakkar, Mustafa

    2014-07-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: might digital drains speed up the time to thoracic drain removal in terms of time till chest drain removal, hospital stay and overall cost? A total of 296 papers were identified as a result of the search as described below. Of these, five papers provided the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the papers are tabulated. A literature search revealed that several single-centre prospective randomized studies have shown significantly earlier removal of chest drains with digital drains ranging between 0.8 and 2.1 days sooner. However, there was heterogeneity in studies in the management protocol of chest drains in terms of the use of suction, number of drains and assessment for drain removal. Some protocols such as routinely keeping drains irrespective of the presence of air leak or drain output may have skewed results. Differences in exclusion criteria and protocols for discharging home with portable devices may have biased results. Due to heterogeneity in the management protocol of chest drains, there is conflicting evidence regarding hospital stay. The limited data on cost suggest that there may be significantly lower postoperative costs in the digital drain group. All the studies were single-centre series generally including patients with good preoperative lung function tests. Further larger studies with more robust chest drain management protocols are required especially to assess length of hospital stay, cost and whether the results are applicable to a larger patient population. PMID:24722516

  10. Photon induced Schottky barrier effects in inverse-extraordinary optoconductance structures

    SciTech Connect

    Tran, L.; Solin, S. A.; Gilbertson, A.; Cohen, L. F.

    2013-12-04

    We expand upon our previous work and characterize the photo-dependence of the effective Schottky barrier in EOC and I-EOC heterostructures by measuring the open circuit voltage and the change in the reverse bias resistance. Under full illumination by a 5 mW, 632.8 nm HeNe laser, the barrier is effectively eliminated and the Ti-GaAs interface becomes Ohmic. The reverse bias resistance changes by a factor of 209 over an illumination intensity change of 10–5:1. While this work illustrates the behavior of the Schottky interface upon illumination, it also demonstrates the effectiveness of the four-point, van der Pauw measurement fundamental to EOC/I-EOC phenomena at monitoring changes in the active region of the mesa. The resistance is largely unaffected by the photovoltaic, DC offset of the surrounding leads, as indicated by the radial symmetry of 2-D resistance maps obtained by rastering the laser across EOC/IEOC devices.

  11. Photon induced Schottky barrier effects in inverse-extraordinary optoconductance structures

    NASA Astrophysics Data System (ADS)

    Tran, L.; Solin, S. A.; Gilbertson, A.; Cohen, L. F.

    2013-12-01

    We expand upon our previous work and characterize the photo-dependence of the effective Schottky barrier in EOC and I-EOC heterostructures by measuring the open circuit voltage and the change in the reverse bias resistance. Under full illumination by a 5 mW, 632.8 nm HeNe laser, the barrier is effectively eliminated and the Ti-GaAs interface becomes Ohmic. The reverse bias resistance changes by a factor of 209 over an illumination intensity change of 10-5:1. While this work illustrates the behavior of the Schottky interface upon illumination, it also demonstrates the effectiveness of the four-point, van der Pauw measurement fundamental to EOC/I-EOC phenomena at monitoring changes in the active region of the mesa. The resistance is largely unaffected by the photovoltaic, DC offset of the surrounding leads, as indicated by the radial symmetry of 2-D resistance maps obtained by rastering the laser across EOC/IEOC devices.

  12. Blood-brain barrier changes with kainic acid-induced limbic seizures

    SciTech Connect

    Zucker, D.K.; Wooten, G.F.; Lothman, E.W.

    1983-02-01

    Rats were treated with kainic acid (KA) i.v. to produce increasingly severe limbic seizures that were monitored with a behavioral rating scale. At various times after the induction of seizures, the animals; blood-brain barriers (B-BB) were studied with alpha-(/sup 14/C)aminoisobutyric acid ((/sup 14/C)AIBA) autoradiography. Using optical density ratios, a coefficient was devised to assess the functional integrity of the B-BB in discrete anatomic regions and to quantitatively compare these measurements among different groups of experimental animals. In animals that exhibited only mild seizures, the B-BB was not different from controls. Animals with severe limbic seizures, however, showed alterations. For as long as 2 h after delivery of KA, the B-BB appeared normal; from 2 to 24 h, the permeability to (/sup 14/C)AIBA was markedly increased throughout the brain, especially in limbic regions; from 24 h to 7 days the B-BB returned to normal except for a small residual change in limbic structures. These findings were confirmed with Evans blue dye studies of the B-BB. A correlation between focal accentuation of B-BB alterations and neuropathologic changes was found. These experiments indicted that recurrent limbic seizures may lead to a breakdown in the B-BB independent of systemic metabolic derangements. Marked focal metabolic and electrical changes, however, occurred in several limbic structures several hours before the blood-brain barrier was altered.

  13. Interleukin-6 induces keratin expression in intestinal epithelial cells: potential role of keratin-8 in interleukin-6-induced barrier function alterations.

    PubMed

    Wang, Lixin; Srinivasan, Shanthi; Theiss, Arianne L; Merlin, Didier; Sitaraman, Shanthi V

    2007-03-16

    Keratin 8 (K8) and keratin-18 (K18) are the major intermediate filament proteins in the intestinal epithelia. The regulation and function of keratin in the intestinal epithelia is largely unknown. In this study we addressed the role and regulation of K8 and K18 expression by interleukin 6 (IL-6). Caco2-BBE cell line and IL-6 null mice were used to study the effect of IL-6 on keratin expression. Keratin expression was studied by Northern blot, Western blot, and confocal microscopy. Paracellular permeability was assessed by apical-to-basal transport of a fluorescein isothiocyanate dextran probe (FD-4). K8 was silenced using the small interfering RNA approach. IL-6 significantly up-regulated mRNA and protein levels of K8 and K18. Confocal microscopy showed a reticular pattern of intracellular keratin localized to the subapical region after IL-6 treatment. IL-6 also induced serine phosphorylation of K8. IL-6 decreased paracellular flux of FD-4 compared with vehicle-treated monolayers. K8 silencing abolished the decrease in paracellular permeability induced by IL-6. Administration of dextran sodium sulfate (DSS) significantly increased intestinal permeability in IL-6-/- mice compared with wild type mice given DSS. Collectively, our data demonstrate that IL-6 regulates the colonic expression of K8 and K18, and K8/K18 mediates barrier protection by IL-6 under conditions where intestinal barrier is compromised. Thus, our data uncover a novel function of these abundant cytoskeletal proteins, which may have implications in intestinal disorders such as inflammatory bowel disease wherein barrier dysfunction underlies the inflammatory response. PMID:17213200

  14. CRF Induces Intestinal Epithelial Barrier Injury via the Release of Mast Cell Proteases and TNF-α

    PubMed Central

    Overman, Elizabeth L.; Rivier, Jean E.; Moeser, Adam J.

    2012-01-01

    Background and Aims Psychological stress is a predisposing factor in the onset and exacerbation of important gastrointestinal diseases including irritable bowel syndrome (IBS) and the inflammatory bowel diseases (IBD). The pathophysiology of stress-induced intestinal disturbances is known to be mediated by corticotropin releasing factor (CRF) but the precise signaling pathways remain poorly understood. Utilizing a porcine ex vivo intestinal model, the aim of this study was to investigate the mechanisms by which CRF mediates intestinal epithelial barrier disturbances. Methodology Ileum was harvested from 6–8 week-old pigs, mounted on Ussing Chambers, and exposed to CRF in the presence or absence of various pharmacologic inhibitors of CRF-mediated signaling pathways. Mucosal-to-serosal flux of 4 kDa-FITC dextran (FD4) and transepithelial electrical resistance (TER) were recorded as indices of intestinal epithelial barrier function. Results Exposure of porcine ileum to 0.05–0.5 µM CRF increased (p<0.05) paracellular flux compared with vehicle controls. CRF treatment had no deleterious effects on ileal TER. The effects of CRF on FD4 flux were inhibited with pre-treatment of tissue with the non-selective CRF1/2 receptor antagonist Astressin B and the mast cell stabilizer sodium cromolyn (10−4 M). Furthermore, anti-TNF-α neutralizing antibody (p<0.01), protease inhibitors (p<0.01) and the neural blocker tetrodotoxin (TTX) inhibited CRF-mediated intestinal barrier dysfunction. Conclusion These data demonstrate that CRF triggers increases in intestinal paracellular permeability via mast cell dependent release of TNF-α and proteases. Furthermore, CRF-mast cell signaling pathways and increases in intestinal permeability require critical input from the enteric nervous system. Therefore, blocking the deleterious effects of CRF may address the enteric signaling of mast cell degranulation, TNFα release, and protease secretion, hallmarks of IBS and IBD. PMID:22768175

  15. LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium

    PubMed Central

    D’Mello, RJ; Caldwell, JM; Azouz, NP; Wen, T; Sherrill, JD; Hogan, SP; Rothenberg, ME

    2015-01-01

    Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus featuring increased esophageal interleukin 13 (IL-13) levels and impaired barrier function. Herein, we investigated leucine-rich repeat–containing protein 31 (LRRC31) in human EoE esophageal tissue and IL-13–treated esophageal epithelial cells. LRRC31 had basal mRNA expression in colonic and airway mucosal epithelium. Esophageal LRRC31 mRNA and protein increased in active EoE and strongly correlated with esophageal eosinophilia and IL13 and CCL26 mRNA expression. IL-13 treatment increased LRRC31 mRNA and protein in air-liquid interface–differentiated esophageal epithelial cells (EPC2s). At baseline, differentiated LRRC31-overexpressing EPC2s had increased barrier function (1.9-fold increase in transepithelial electrical resistance [P < 0.05] and 2.8-fold decrease in paracellular flux [P < 0.05]). RNA sequencing analysis of differentiated LRRC31-overexpressing EPC2s identified 38 dysregulated genes (P < 0.05), including 5 kallikrein (KLK) serine proteases. Notably, differentiated LRRC31-overexpressing EPC2s had decreased KLK expression and activity, whereas IL-13–treated, differentiated LRRC31 gene-silenced EPC2s had increased KLK expression and suprabasal epithelial detachment. We identified similarly dysregulated KLK expression in the esophagus of patients with active EoE and in IL-13–treated esophageal epithelial cells. We propose that LRRC31 is induced by IL-13 and modulates epithelial barrier function, potentially through KLK regulation. PMID:26462420

  16. How to remove a chest drain.

    PubMed

    Allibone, Elizabeth

    2015-10-01

    RATIONALE AND KEY POINTS: This article aims to help nurses to undertake the removal of a chest drain in a safe, effective and patient-centred manner. This procedure requires two practitioners. The chest drain will have been inserted aseptically to remove air, blood, fluid or pus from the pleural cavity. ▶ Chest drains may be small or wide bore depending on the underlying condition and clinical setting. They may be secured with a mattress suture and/or an anchor suture. ▶ Chest drains are usually removed under medical instructions when the patient's lung has inflated, the underlying condition has resolved, there is no evidence of respiratory compromise or failure, and their anticoagulation status has been assessed as satisfactory. ▶ Chest drains secured with a mattress suture should be removed by two practitioners. One practitioner is required to remove the tube and the other to tie the mattress suture (if present) and secure the site. REFLECTIVE ACTIVITY: Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How reading this article will change your practice. 2. How this article could be used to educate patients with chest drains. Subscribers can upload their reflective accounts at: rcni.com/portfolio . PMID:26443174

  17. Dielectric Barrier Discharge Plasma-Induced Photocatalysis and Ozonation for the Treatment of Wastewater

    NASA Astrophysics Data System (ADS)

    Mok, Young Sun; Jo, Jin-Oh; Lee, Heon-Ju

    2008-02-01

    The physicochemical processes of dielectric barrier discharge (DBD) such as in-situ formation of chemically active species and emission of ultraviolet (UV)/visible light were utilized for the treatment of a simulated wastewater formed with Acid Red 4 as the model organic contaminant. The chemically active species (mostly ozone) produced in the DBD reactor were well distributed in the wastewater using a porous gas diffuser, thereby increasing the gas-liquid contact area. For the purpose of making the best use of the light emission, a titanium oxide-based photocatalyst was incorporated in the wastewater treating system. The experimental parameters chosen were the voltage applied to the DBD reactor, the initial pH of the wastewater, and the concentration of hydrogen peroxide added to the wastewater. The results have clearly shown that the present system capable of degrading organic contaminants in two ways (photocatalysis and ozonation) may be a promising wastewater treatment technology.

  18. Effects of Barrier-Induced Nuclear Spin Magnetization Inhomogeneities on Diffusion-Attenuated MR Signal

    PubMed Central

    Sukstanskii, A.L.; Ackerman, J.J.H.; Yablonskiy, D.A.

    2007-01-01

    The spatial distribution of the transverse nuclear spin magnetization, appearing in a single compartment with impermeable boundaries in a Stejskal-Tanner gradient pulse MR experiment, is analyzed in detail. At short diffusion times the presence of diffusion-restrictive barriers (membranes) reduces effective diffusivity near the membranes and leads to an inhomogeneous spin magnetization distribution (the edge-enhancement effect). In this case, the signal reveals a quasi-two-compartment behavior and can be empirically modeled remarkably well by a biexponential function. The current results provide a framework for interpreting experimental MR data on various phenoma, including water diffusion in giant axons, metabolite diffusion in the brain, and hyperpolarized gas diffusion in lung airways. PMID:14523959

  19. Desiccation-Induced Volumetric Shrinkage of Compacted Metakaolin-Treated Black Cotton Soil for a Hydraulic Barriers System

    NASA Astrophysics Data System (ADS)

    Moses, George; Peter, Oriola F. O.; Osinubi, Kolawole J.

    2016-03-01

    Black cotton soil treated with up to 24% metakaolin (MCL) content was prepared by molding water contents of -2, 0, 2, 4 and 6% of optimum moisture content (OMC) and compacted with British Standard Light (BSL) and West African Standard (WAS) or `Intermediate' energies. The specimens were extruded from the compaction molds and allowed to air dry in a laboratory in order to assess the effect of desiccation-induced shrinkage on the compacted mix for use as a hydraulic barrier in a waste containment application. The results recorded show that the volumetric shrinkage strain (VSS) values were large within the first 10 days of drying; the VSS values increased with a higher molding of the water content, relative to the OMC. The VSS generally increased with a higher initial degree of saturation for the two compactive efforts, irrespective of the level of MCL treatment. Generally, the VSS decreased with an increasing MCL content. Only specimens treated with a minimum 20% MCL content and compacted with the WAS energy satisfied the regulatory maximum VSS of 4% for use as a hydraulic barrier.

  20. Controlled aluminum-induced crystallization of an amorphous silicon thin film by using an oxide-layer diffusion barrier

    NASA Astrophysics Data System (ADS)

    Hwang, Ji-Hyun; Kwak, Hyunmin; Kwon, Myeung Hoi

    2014-03-01

    Aluminum-induced crystallization (AIC) of amorphous silicon with an Al2O3 diffusion barrier was investigated for controlling Si crystallization and preventing layer exchange during the annealing process. An Al2O3 layer was deposited between the a-Si and the Al films (a-Si/Al2O3/Al/Glass) and was blasted with an air spray gun with alumina beads to form diffusion channels between the Si and the Al layers. During the annealing process, small grain Si x Al seeds were formed at the channels. Then, the Al2O3 diffusion barrier was restructured to close the channels and prevent further diffusion of Al atoms into the a-Si layer. A polycrystalline Si film with (111), (220) and (311) crystallization peaks in the X-ray diffraction pattern was formed by annealing at 560 °C in a conventional furnace. That film showed a p-type semiconducting behavior with good crystallinity and a large grain size of up to 14.8 µm. No layer conversion occurred between the Si and the Al layers, which had been the fundamental obstacle to the applications in the crystallization of a-Si films by using the AIC method.

  1. Retinoic Acid Prevents Disruption of Blood-Spinal Cord Barrier by Inducing Autophagic Flux After Spinal Cord Injury.

    PubMed

    Zhou, Yulong; Zheng, Binbin; Ye, Libing; Zhang, Hongyu; Zhu, Sipin; Zheng, Xiaomeng; Xia, Qinghai; He, Zili; Wang, Qingqing; Xiao, Jian; Xu, Huazi

    2016-04-01

    Spinal cord injury (SCI) induces the disruption of the blood-spinal cord barrier (BSCB), which leads to infiltration of blood cells, inflammatory responses and neuronal cell death, with subsequent development of spinal cord secondary damage. Recent reports pointed to an important role of retinoic acid (RA), the active metabolite of the vitamin A, in the induction of the blood-brain barrier (BBB) during human and mouse development, however, it is unknown whether RA plays a role in maintaining BSCB integrity under the pathological conditions such as SCI. In this study, we investigated the BSCB protective role of RA both in vivo and in vitro and demonstrated that autophagy are involved in the BSCB protective effect of RA. Our data show that RA attenuated BSCB permeability and also attenuated the loss of tight junction molecules such as P120, β-catenin, Occludin and Claudin5 after injury in vivo as well as in brain microvascular endothelial cells. In addition, RA administration improved functional recovery of the rat model of trauma. We also found that RA could significantly increase the expression of LC3-II and decrease the expression of p62 both in vivo and in vitro. Furthermore, combining RA with the autophagy inhibitor chloroquine (CQ) partially abolished its protective effect on the BSCB and exacerbated the loss of tight junctions. Together, our studies indicate that RA improved functional recovery in part by the prevention of BSCB disruption via the activation of autophagic flux after SCI. PMID:26582233

  2. Electrochemically induced dual reactive barriers for transformation of TCE and mixture of contaminants in groundwater

    PubMed Central

    Mao, Xuhui; Yuan, Songhu; Fallahpour, Noushin; Ciblak, Ali; Howard, Joniqua; Padilla, Ingrid; Loch-Caruso, Rita; Alshawabkeh, Akram N.

    2012-01-01

    A novel reactive electrochemical flow system consisting of iron anode and porous cathode is proposed for the remediation of mixture of contaminants in groundwater. The system consists of a series of sequentially arranged electrodes, a perforated iron anode, a porous copper cathode followed by a mesh-type mixed metal oxide anode. The iron anode generates ferrous species and a chemically reducing environment, the porous cathode provides a reactive electrochemically reducing barrier, and the inert anode provides proton and oxygen to neutralize the system. The redox conditions of the electrolyte flowing through this system can be regulated by controlling the distribution of the electric current. Column experiments are conducted to evaluate the process and study the variables. The electrochemical reduction on a copper foam cathode produced an electrode-based reductive potential capable of reducing TCE and nitrate. Rational electrodes arrangement, longer residence time of electrolytes and higher surface area of foam electrode improve the reductive transformation of TCE. More than 82.2% TCE removal efficiency is achieved for the case of low influent concentration (< 7.5 mg/L) and high current (> 45 mA). The ferrous species produced from the iron anode not only enhance the transformation of TCE on the cathode, but also facilitates transformation of other contaminants including dichromate, selenate and arsenite. Removal efficiencies greater than 80% are achieved for these contaminants from flowing contaminated water. The overall system, comprising the electrode-based and electrolyte-based barriers, can be engineered as a versatile and integrated remedial method for a relatively wide spectrum of contaminants and their mixtures. PMID:23067023

  3. Focal MMP-2 and MMP-9 activity at the blood-brain barrier promotes chemokine-induced leukocyte migration.

    PubMed

    Song, Jian; Wu, Chuan; Korpos, Eva; Zhang, Xueli; Agrawal, Smriti M; Wang, Ying; Faber, Cornelius; Schäfers, Michael; Körner, Heinrich; Opdenakker, Ghislain; Hallmann, Rupert; Sorokin, Lydia

    2015-02-24

    Although chemokines are sufficient for chemotaxis of various cells, increasing evidence exists for their fine-tuning by selective proteolytic processing. Using a model of immune cell chemotaxis into the CNS (experimental autoimmune encephalomyelitis [EAE]) that permits precise localization of immigrating leukocytes at the blood-brain barrier, we show that, whereas chemokines are required for leukocyte migration into the CNS, additional MMP-2/9 activities specifically at the border of the CNS parenchyma strongly enhance this transmigration process. Cytokines derived from infiltrating leukocytes regulate MMP-2/9 activity at the parenchymal border, which in turn promotes astrocyte secretion of chemokines and differentially modulates the activity of different chemokines at the CNS border, thereby promoting leukocyte migration out of the cuff. Hence, cytokines, chemokines, and cytokine-induced MMP-2/9 activity specifically at the inflammatory border collectively act to accelerate leukocyte chemotaxis across the parenchymal border. PMID:25704809

  4. Quantifying redox-induced Schottky barrier variations in memristive devices via in operando spectromicroscopy with graphene electrodes.

    PubMed

    Baeumer, Christoph; Schmitz, Christoph; Marchewka, Astrid; Mueller, David N; Valenta, Richard; Hackl, Johanna; Raab, Nicolas; Rogers, Steven P; Khan, M Imtiaz; Nemsak, Slavomir; Shim, Moonsub; Menzel, Stephan; Schneider, Claus Michael; Waser, Rainer; Dittmann, Regina

    2016-01-01

    The continuing revolutionary success of mobile computing and smart devices calls for the development of novel, cost- and energy-efficient memories. Resistive switching is attractive because of, inter alia, increased switching speed and device density. On electrical stimulus, complex nanoscale redox processes are suspected to induce a resistance change in memristive devices. Quantitative information about these processes, which has been experimentally inaccessible so far, is essential for further advances. Here we use in operando spectromicroscopy to verify that redox reactions drive the resistance change. A remarkable agreement between experimental quantification of the redox state and device simulation reveals that changes in donor concentration by a factor of 2-3 at electrode-oxide interfaces cause a modulation of the effective Schottky barrier and lead to >2 orders of magnitude change in device resistance. These findings allow realistic device simulations, opening a route to less empirical and more predictive design of future memory cells. PMID:27539213

  5. Quantifying redox-induced Schottky barrier variations in memristive devices via in operando spectromicroscopy with graphene electrodes

    PubMed Central

    Baeumer, Christoph; Schmitz, Christoph; Marchewka, Astrid; Mueller, David N.; Valenta, Richard; Hackl, Johanna; Raab, Nicolas; Rogers, Steven P.; Khan, M. Imtiaz; Nemsak, Slavomir; Shim, Moonsub; Menzel, Stephan; Schneider, Claus Michael; Waser, Rainer; Dittmann, Regina

    2016-01-01

    The continuing revolutionary success of mobile computing and smart devices calls for the development of novel, cost- and energy-efficient memories. Resistive switching is attractive because of, inter alia, increased switching speed and device density. On electrical stimulus, complex nanoscale redox processes are suspected to induce a resistance change in memristive devices. Quantitative information about these processes, which has been experimentally inaccessible so far, is essential for further advances. Here we use in operando spectromicroscopy to verify that redox reactions drive the resistance change. A remarkable agreement between experimental quantification of the redox state and device simulation reveals that changes in donor concentration by a factor of 2–3 at electrode-oxide interfaces cause a modulation of the effective Schottky barrier and lead to >2 orders of magnitude change in device resistance. These findings allow realistic device simulations, opening a route to less empirical and more predictive design of future memory cells. PMID:27539213

  6. Surgery-Induced Hippocampal Angiotensin II Elevation Causes Blood-Brain Barrier Disruption via MMP/TIMP in Aged Rats

    PubMed Central

    Li, Zhengqian; Mo, Na; Li, Lunxu; Cao, Yiyun; Wang, Wenming; Liang, Yaoxian; Deng, Hui; Xing, Rui; Yang, Lin; Ni, Cheng; Chui, Dehua; Guo, Xiangyang

    2016-01-01

    Reversible blood-brain barrier (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 of MMP (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 (PPARγ) 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. PMID:27199659

  7. Targeted Drug Delivery with Focused Ultrasound-Induced Blood-Brain Barrier Opening Using Acoustically-Activated Nanodroplets

    PubMed Central

    Chen, Cherry C.; Sheeran, Paul S.; Wu, Shih-Ying; Olumolade, Oluyemi O.; Dayton, Paul A.; Konofagou, Elisa E.

    2013-01-01

    Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. More homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. PMID:24096019

  8. Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells.

    PubMed

    Jumnongprakhon, Pichaya; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

    2016-09-01

    Melatonin is a neurohormone and has high potent of antioxidant that is widely reported to be active against methamphetamine (METH)-induced toxicity to neuron, glial cells, and brain endothelial cells. However, the role of melatonin on the inflammatory responses which are mostly caused by blood-brain barrier (BBB) impairment by METH administration has not been investigated. This study used the primary rat brain microvascular endothelial cells (BMVECs) to determine the protective mechanism of melatonin on METH-induced inflammatory responses in the BBB via nuclear factor-ĸB (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Herein, we demonstrated that melatonin reduced the level of the inflammatory mediators, including intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, matrix metallopeptidase (MMP)-9, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) caused by METH. These responses were related to the decrease of the expression and translocation of the NF-κB p65 subunit and the activity of NADPH oxidase (NOX)-2. In addition, melatonin promoted the antioxidant processes, modulated the expression and translocation of Nrf2, and also increased the level of heme oxygenase (HO)-1, NAD (P) H: quinone oxidoreductase (NQO)-1, γ-glutamylcysteine synthase (γ-GCLC), and the activity of superoxide dismutase (SOD) through NOX2 mechanism. In addition, we found that the protective role of melatonin in METH-induced inflammatory responses in the BBB was mediated through melatonin receptors (MT1/2). We concluded that the interaction of melatonin with its receptor prevented METH-induced inflammatory responses by suppressing the NF-κB signaling and promoting the Nrf2 signaling before BBB impairment. PMID:27268413

  9. Pentylentetrazole-induced loss of blood-brain barrier integrity involves excess nitric oxide generation by neuronal nitric oxide synthase.

    PubMed

    Danjo, Sonoko; Ishihara, Yasuhiro; Watanabe, Masatomo; Nakamura, Yu; Itoh, Kouichi

    2013-09-12

    Dysfunction of the blood-brain barrier (BBB) is one of the major pathophysiological consequences of epilepsy. The increase in the permeability caused by BBB failure is thought to contribute to the development of epileptic outcomes. We developed a method by which the BBB permeability can be demonstrated by gadolinium-enhanced T1 weighted imaging (GdET1WI). The present study examined the changes in the BBB permeability in mice with generalized convulsive seizures (GCS) induced by acute pentylentetrazole (PTZ) injection. At 15min after PTZ-induced GCS, the BBB temporarily leaks BBB-impermeable contrast agent into the parenchyma of the diencephalon, hippocampus and cerebral cortex in mice, and the loss of BBB integrity was gradually recovered by 24h. The temporary BBB failure is a critical link to the glutamatergic activities that occur following the injection of PTZ. PTZ activates the glutamatergic pathway via the NMDA receptor, then nitric oxide (NO) is generated by NMDA receptor-coupled neuronal NO synthase (nNOS). To examine the influence of nNOS-derived NO induced by PTZ on the increases of the BBB permeability, GdET1WI was performed using conventional nNOS gene-deficient mice with or without PTZ injection. The failure of the BBB induced by PTZ was completely protected by nNOS deficiency in the brain. These results suggest that nNOS-derived excess NO in the glutamatergic pathway plays a key role in the failure of the BBB during PTZ-induced GCS. The levels of NO synthetized by nNOS in the brain may represent an important target for the future development of drugs to protect the BBB. PMID:23831997

  10. P-glycoprotein activity in the blood-brain barrier is affected by virus-induced neuroinflammation and antipsychotic treatment.

    PubMed

    Doorduin, Janine; de Vries, Erik F J; Dierckx, Rudi A; Klein, Hans C

    2014-10-01

    A large percentage of schizophrenic patients respond poorly to antipsychotic treatment. This could be explained by inefficient drug transport across the blood-brain barrier due to P-glycoprotein mediated efflux. P-glycoprotein activity and expression in the blood-brain barrier can be affected by inflammation and pharmacotherapy. We therefore investigated the effect of herpes simplex virus type-1 (HSV-1) induced neuroinflammation and antipsychotic treatment on P-glycoprotein activity. Rats were inoculated with HSV-1 or PBS (control) on day 0 and treated with saline, clozapine or risperidone from day 0 up until day 4 post-inoculation. Positron emission tomography with the P-glycoprotein substrate [11C]verapamil was used to assess P-glycoprotein activity at day 6 post-inoculation. Disease symptoms in HSV-1 inoculated rats increased over time and were not significantly affected by treatment. The volume of distribution (VT) of [11C]verapamil was significantly lower (10-22%) in HSV-1 inoculated rats than in control rats. In addition, antipsychotic treatment significantly affected the VT of [11C]verapamil in all brain regions, although this effect was drug dependent. In fact, VT of [11C]verapamil was significantly increased (22-39%) in risperidone treated rats in most brain regions when compared to clozapine treated rats and in midbrain when compared to saline treated rats. No interaction between HSV-1 inoculation and antipsychotic treatment on VT of [11C]verapamil was found. In this study we demonstrated that HSV-1 induced neuroinflammation increased and risperidone treatment decreased P-glycoprotein activity. This finding is of importance for the understanding of treatment resistance in schizophrenia, and warrants further investigation of the underlying mechanism and the importance in clinical practice. PMID:24973705

  11. Lipopolysaccharide-Induced Middle Ear Inflammation Disrupts the cochlear Intra-Strial Fluid–Blood Barrier through Down-Regulation of Tight Junction Proteins

    PubMed Central

    Zhang, Jinhui; Chen, Songlin; Hou, Zhiqiang; Cai, Jing; Dong, Mingmin; Shi, Xiaorui

    2015-01-01

    Middle ear infection (or inflammation) is the most common pathological condition that causes fluid to accumulate in the middle ear, disrupting cochlear homeostasis. Lipopolysaccharide, a product of bacteriolysis, activates macrophages and causes release of inflammatory cytokines. Many studies have shown that lipopolysaccharides cause functional and structural changes in the inner ear similar to that of inflammation. However, it is specifically not known how lipopolysaccharides affect the blood-labyrinth barrier in the stria vascularis (intra-strial fluid–blood barrier), nor what the underlying mechanisms are. In this study, we used a cell culture-based in vitro model and animal-based in vivo model, combined with immunohistochemistry and a vascular leakage assay, to investigate lipopolysaccharide effects on the integrity of the mouse intra-strial fluid–blood barrier. Our results show lipopolysaccharide-induced local infection significantly affects intra-strial fluid–blood barrier component cells. Pericytes and perivascular-resident macrophage-like melanocytes are particularly affected, and the morphological and functional changes in these cells are accompanied by substantial changes in barrier integrity. Significant vascular leakage is found in the lipopolysaccharide treated-animals. Consistent with the findings from the in vivo animal model, the permeability of the endothelial cell monolayer to FITC-albumin was significantly higher in the lipopolysaccharide-treated monolayer than in an untreated endothelial cell monolayer. Further study has shown the lipopolysaccharide-induced inflammation to have a major effect on the expression of tight junctions in the blood barrier. Lipopolysaccharide was also shown to cause high frequency hearing loss, corroborated by previous reports from other laboratories. Our findings show lipopolysaccharide-evoked middle ear infection disrupts inner ear fluid balance, and its particular effects on the intra-strial fluid

  12. Facilitating climate-change-induced range shifts across continental land-use barriers.

    PubMed

    Robillard, Cassandra M; Coristine, Laura E; Soares, Rosana N; Kerr, Jeremy T

    2015-12-01

    Climate changes impose requirements for many species to shift their ranges to remain within environmentally tolerable areas, but near-continuous regions of intense human land use stretching across continental extents diminish dispersal prospects for many species. We reviewed the impact of habitat loss and fragmentation on species' abilities to track changing climates and existing plans to facilitate species dispersal in response to climate change through regions of intensive land uses, drawing on examples from North America and elsewhere. We identified an emerging analytical framework that accounts for variation in species' dispersal capacities relative to both the pace of climate change and habitat availability. Habitat loss and fragmentation hinder climate change tracking, particularly for specialists, by impeding both propagule dispersal and population growth. This framework can be used to identify prospective modern-era climatic refugia, where the pace of climate change has been slower than surrounding areas, that are defined relative to individual species' needs. The framework also underscores the importance of identifying and managing dispersal pathways or corridors through semi-continental land use barriers that can benefit many species simultaneously. These emerging strategies to facilitate range shifts must account for uncertainties around population adaptation to local environmental conditions. Accounting for uncertainties in climate change and dispersal capabilities among species and expanding biological monitoring programs within an adaptive management paradigm are vital strategies that will improve species' capacities to track rapidly shifting climatic conditions across landscapes dominated by intensive human land use. PMID:26193759

  13. Wire-cylinder dielectric barrier discharge induced degradation of aqueous atrazine.

    PubMed

    Zhu, Dan; Jiang, Lin; Liu, Run-Long; Chen, Pei; Lang, Lin; Feng, Jing-Wei; Yuan, Shou-Jun; Zhao, Da-Yong

    2014-12-01

    The wire-cylinder dielectric barrier discharge reactor was adopted for removal of aqueous atrazine. The effect of different parameters on the degradation efficiency of atrazine was investigated, and the degradation mechanism of atrazine was studied. The experimental results showed that when the discharge power was 50 W and the air flow rate was 140 L h(-1), 93.7% of atrazine was degraded after 18 min of discharge time. The concentrations of generated O3 and H2O2 increased with increasing discharge time. The pH decreased from 6.80 to 2.50, 12.7% of TOC was removed after 18 min. The concentrations of generated Cl(-) and NO3(-) increased significantly during the degradation process of atrazine, and the decreasing toxicity trend was observed for the treated atrazine solution. The degradation byproducts of atrazine were identified using liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS), which might be formed mainly in dechlorination hydroxylation, alkyl oxidation, dechlorination hydroxylation combined with alkyl oxidation and demethylation oxidation reactions. PMID:25268075

  14. Spontaneous versus induced hydrogen and deuterium helical shaped plasmas with electron internal transport barriers

    NASA Astrophysics Data System (ADS)

    Gobbin, M.; Franz, P.; Auriemma, F.; Lorenzini, R.; Marrelli, L.

    2015-09-01

    Electron internal transport barriers (eITBs) in high current plasmas with helical equilibria of the reversed field pinch experiment RFX-mod are analyzed and characterized in detail thanks to a high time resolution double filter diagnostic for the electron temperature spatial profile determination. The large amount of data provided by this diagnostic has required the development of dedicated algorithms and the identification of suitable parameters, reported and described in this paper, in order to perform automatic statistical studies. These numerical tools have been used to examine the effect of three dimensional (3D) magnetic fields applied by the RFX-mod 192 active coils in deuterium and hydrogen discharges with the aim to improve the sustainment and control of helical equilibria with eITBs. It is shown that 3D fields partially increase the occurring of helical states but with only a moderate effect on the eITBs duration; moreover, they have a different impact on the confinement properties in hydrogen and deuterium discharges. Numerical simulations, by the Hamiltonian guiding center code ORBIT, investigate the effect of magnetic topology in plasmas with and without the application of 3D fields on deuterium and hydrogen test ions transport. Results from numerical studies are in agreement with estimates of the particle confinement times showing that particle transport is reduced in deuterium plasmas but not significantly affected by the application of helical boundary conditions.

  15. Wet decontamination-induced stratum corneum hydration--effects on the skin barrier function to diethylmalonate.

    PubMed

    Loke, W K; U, S H; Lau, S K; Lim, J S; Tay, G S; Koh, C H

    1999-01-01

    Decontamination of chemical agents from the skin uses both dry and wet decontamination processes. Recent studies have shown that wet decontamination frequently results in stratum corneum hydration. To evaluate the hydration effect of wet decontamination on the skin barrier function and hence on the decontamination efficiency, a series of comparative studies were carried out on human skin contaminated with the nerve agent simulant diethylmalonate, using decontamination media having different salinity and surfactants. The results showed that, compared to non-decontaminated skin, remnant diethylmalonate on decontaminated skin penetrated at an accelerated rate in the immediate 2 h following decontamination. This transient enhancement effect, ranging from 20 to 98%, was depended on the nature of the decontamination media used and was more obvious in skin samples that were decontaminated 1 h postexposure. All decontamination media exhibited this effect, with the greatest enhancement observed in the following order: anionic surfactant > cationic surfactant > non-ionic surfactant > deionized water > 0.9% saline > 9% saline. PMID:10439344

  16. TLR4 induces CCR7-dependent monocytes transmigration through the blood-brain barrier.

    PubMed

    Paradis, Alexandre; Bernier, Stéphane; Dumais, Nancy

    2016-06-15

    In this study, we examined whether bacterial pathogen-associated molecular patterns recognized by toll-like receptors (TLRs) can modify the CCR7-dependent migration of human monocytes. MonoMac-1 (MM-1) cells and freshly isolated human monocytes were cultivated in the presence of agonists for TLR4 (which senses lipopolysaccharides from gram-negative bacteria), TLR1/2 (which senses peptidoglycan from gram-positive bacteria), and TLR9 (which recognizes bacterial DNA rich in unmethylated CpG DNA). CCR7 mRNA transcription was measured using quantitative reverse transcription polymerase chain reaction and protein expression was examined using flow cytometry. CCR7 function was monitored using migration and transmigration assays in response to CCL19/CCL21, which are natural ligands for CCR7. Our results show that TLR4 strongly increases monocyte migratory capacity in response to CCL19 in chemotaxis and transmigration assays in a model that mimics the human blood-brain barrier, whereas TLR1/2 and 9 have no effect. Examination of monocyte migration in response to TLRs that are activated by bacterial components would contribute to understanding the excessive monocyte migration that characterizes the pathogenesis of bacterial infections and/or neuroinflammatory diseases. PMID:27235343

  17. Improved Ethanol Production from Xylose by Candida shehatae Induced by Dielectric Barrier Discharge Air Plasma

    NASA Astrophysics Data System (ADS)

    Chen, Huixia; Xiu, Zhilong; Bai, Fengwu

    2014-06-01

    Xylose fermentation is essential for ethanol production from lignocellulosic biomass. Exposure of the xylose-fermenting yeast Candida shehatae (C. shehatae) CICC1766 to atmospheric pressure dielectric barrier discharge (DBD) air plasma yields a clone (designated as C81015) with stability, which exhibits a higher ethanol fermentation rate from xylose, giving a maximal enhancement in ethanol production of 36.2% compared to the control (untreated). However, the biomass production of C81015 is lower than that of the control. Analysis of the NADH (nicotinamide adenine dinucleotide)- and NADPH (nicotinamide adenine dinucleotide phosphate)-linked xylose reductases and NAD+-linked xylitol dehydrogenase indicates that their activities are enhanced by 34.1%, 61.5% and 66.3%, respectively, suggesting that the activities of these three enzymes are responsible for improving ethanol fermentation in C81015 with xylose as a substrate. The results of this study show that DBD air plasma could serve as a novel and effective means of generating microbial strains that can better use xylose for ethanol fermentation.

  18. Polyinosinic:polycytidylic acid induces protein kinase D–dependent disassembly of apical junctions and barrier dysfunction in airway epithelial cells

    PubMed Central

    Rezaee, Fariba; Meednu, Nida; Emo, Jason A.; Saatian, Bahman; Chapman, Timothy J.; Naydenov, Nayden G.; De Benedetto, Anna; Beck, Lisa A.; Ivanov, Andrei I.; Georas, Steve N.

    2011-01-01

    Background Disruption of the epithelial barrier might be a risk factor for allergen sensitization and asthma. Viral respiratory tract infections are strongly associated with asthma exacerbation, but the effects of respiratory viruses on airway epithelial barrier function are not well understood. Many viruses generate double-stranded RNA, which can lead to airway inflammation and initiate an antiviral immune response. Objectives We investigated the effects of the synthetic double-stranded RNA polyinosinic:polycytidylic acid (polyI:C) on the structure and function of the airway epithelial barrier in vitro. Methods 16HBE14o- human bronchial epithelial cells and primary airway epithelial cells at an air-liquid interface were grown to confluence on Transwell inserts and exposed to polyI:C. We studied epithelial barrier function by measuring transepithelial electrical resistance and paracellular flux of fluorescent markers and structure of epithelial apical junctions by means of immunofluorescence microscopy. Results PolyI:C induced a profound decrease in transepithelial electrical resistance and increase in paracellular permeability. Immunofluorescence microscopy revealed markedly reduced junctional localization of zonula occludens-1, occludin, E-cadherin, β-catenin, and disorganization of junction-associated actin filaments. PolyI:C induced protein kinase D (PKD) phosphorylation, and a PKD antagonist attenuated polyI:C-induced disassembly of apical junctions and barrier dysfunction. Conclusions PolyI:C has a powerful and previously unsuspected disruptive effect on the airway epithelial barrier. PolyI:C-dependent barrier disruption is mediated by disassembly of epithelial apical junctions, which is dependent on PKD signaling. These findings suggest a new mechanism potentially underlying the associations between viral respiratory tract infections, airway inflammation, and allergen sensitization. PMID:21996340

  19. Scalability of Schottky barrier metal-oxide-semiconductor transistors

    NASA Astrophysics Data System (ADS)

    Jang, Moongyu

    2016-05-01

    In this paper, the general characteristics and the scalability of Schottky barrier metal-oxide-semiconductor field effect transistors (SB-MOSFETs) are introduced and reviewed. The most important factors, i.e., interface-trap density, lifetime and Schottky barrier height of erbium-silicided Schottky diode are estimated using equivalent circuit method. The extracted interface trap density, lifetime and Schottky barrier height for hole are estimated as 1.5 × 1013 traps/cm2, 3.75 ms and 0.76 eV, respectively. The interface traps are efficiently cured by N2 annealing. Based on the diode characteristics, various sizes of erbium-silicided/platinum-silicided n/p-type SB-MOSFETs are manufactured and analyzed. The manufactured SB-MOSFETs show enhanced drain induced barrier lowering (DIBL) characteristics due to the existence of Schottky barrier between source and channel. DIBL and subthreshold swing characteristics are comparable with the ultimate scaling limit of double gate MOSFETs which shows the possible application of SB-MOSFETs in nanoscale regime.

  20. Bacterial lipopolysaccharide induces actin reorganization, intercellular gap formation, and endothelial barrier dysfunction in pulmonary vascular endothelial cells: concurrent F-actin depolymerization and new actin synthesis.

    PubMed

    Goldblum, S E; Ding, X; Brann, T W; Campbell-Washington, J

    1993-10-01

    Bacterial lipopolysaccharide (LPS) influences pulmonary vascular endothelial barrier function in vitro. We studied whether LPS regulates endothelial barrier function through actin reorganization. Postconfluent bovine pulmonary artery endothelial cell monolayers were exposed to Escherichia coli 0111:B4 LPS 10 ng/ml or media for up to 6 h and evaluated for: 1) transendothelial 14C-albumin flux, 2) F-actin organization with fluorescence microscopy, 3) F-actin quantitation by spectrofluorometry, and 4) monomeric G-actin levels by the DNAse 1 inhibition assay. LPS induced increments in 14C-albumin flux (P < 0.001) and intercellular gap formation at > or = 2-6 h. During this same time period the endothelial F-actin pool was not significantly changed compared to simultaneous media controls. Mean (+/- SE) G-actin (micrograms/mg total protein) was significantly (P < 0.002) increased compared to simultaneous media controls at 2, 4, and 6 h but not at 0.5 or 1 h. Prior F-actin stabilization with phallicidin protected against the LPS-induced increments in G-actin (P = 0.040) as well as changes in barrier function (P < 0.0001). Prior protein synthesis inhibition unmasked an LPS-induced decrement in F-actin (P = 0.0044), blunted the G-actin increment (P = 0.010), and increased LPS-induced changes in endothelial barrier function (P < 0.0001). Therefore, LPS induces pulmonary vascular endothelial F-actin depolymerization, intercellular gap formation, and barrier dysfunction. Over the same time period, LPS increased total actin (P < 0.0001) and new actin synthesis (P = 0.0063) which may be a compensatory endothelial cell response to LPS-induced F-actin depolymerization. PMID:8408232

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