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Sample records for tslp regulates barrier

  1. TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling.

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    Zhong, Jun; Sharma, Jyoti; Raju, Rajesh; Palapetta, Shyam Mohan; Prasad, T S Keshava; Huang, Tai-Chung; Yoda, Akinori; Tyner, Jeffrey W; van Bodegom, Diederik; Weinstock, David M; Ziegler, Steven F; Pandey, Akhilesh

    2014-01-01

    Thymic stromal lymphopoietin (TSLP) is a four-helix bundle cytokine that plays a critical role in the regulation of immune responses and in the differentiation of hematopoietic cells. TSLP signals through a heterodimeric receptor complex consisting of an interleukin-7 receptor α chain and a unique TSLP receptor (TSLPR) [also known as cytokine receptor-like factor 2 (CRLF2)]. Cellular targets of TSLP include dendritic cells, B cells, mast cells, regulatory T (Treg) cells and CD4+ and CD8+ T cells. The TSLP/TSLPR axis can activate multiple signaling transduction pathways including the JAK/STAT pathway and the PI-3 kinase pathway. Aberrant TSLP/TSLPR signaling has been associated with a variety of human diseases including asthma, atopic dermatitis, nasal polyposis, inflammatory bowel disease, eosinophilic eosophagitis and, most recently, acute lymphoblastic leukemia. A centralized resource of the TSLP signaling pathway cataloging signaling events is not yet available. In this study, we present a literature-annotated resource of reactions in the TSLP signaling pathway. This pathway map is publicly available through NetPath (http://www.netpath.org/), an open access signal transduction pathway resource developed previously by our group. This map includes 236 molecules and 252 reactions that are involved in TSLP/TSLPR signaling pathway. We expect that the TSLP signaling pathway map will provide a rich resource to study the biology of this important cytokine as well as to identify novel therapeutic targets for diseases associated with dysregulated TSLP/TSLPR signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_24.

  2. Cellular and Molecular Mechanisms of TSLP Function in Human Allergic Disorders - TSLP Programs the “Th2 code” in Dendritic Cells

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    Ito, Tomoki; Liu, Yong-Jun; Arima, Kazuhiko

    2013-01-01

    Thymic stromal lymphopoietin (TSLP) has been recently implicated as a key molecule for initiating allergic inflammation at the epithelial cell-dendritic cell (DC) interface. In humans, aberrant TSLP expression is observed in allergic tissues, such as lesional skins of atopic dermatitis, lungs of asthmatics, nasal mucosa of atopic rhinitis and nasal polyps, and ocular surface of allergic keratoconjunctivitis. TSLP is produced predominantly by damaged epithelial cells and stimulates myeloid DCs (mDCs). TSLP-activated mDCs can promote the differentiation of naïve CD4+ T cells into a Th2 phenotype and the expansion of CD4+ Th2 memory cells in a unique manner dependent on OX40L, one of the tumor necrosis factor superfamily members with Th2-promoting function, and lack of production of IL-12. From a genetic point of view, multiple genome-wide association studies have repeatedly identified the TSLP gene as one of the loci associated with susceptibility to allergic diseases. Thus, TSLP is a rational therapeutic target for the treatment of allergic disorders. Elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype is essential for developing anti-TSLP therapy. PMID:22189594

  3. Multiple Functions of the New Cytokine-Based Antimicrobial Peptide Thymic Stromal Lymphopoietin (TSLP

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    Louise Bjerkan

    2016-07-01

    Full Text Available Thymic stromal lymphopoietin (TSLP is a pleiotropic cytokine, hitherto mostly known to be involved in inflammatory responses and immunoregulation. The human tslp gene gives rise to two transcription and translation variants: a long form (lfTSLP that is induced by inflammation, and a short, constitutively-expressed form (sfTSLP, that appears to be downregulated by inflammation. The TSLP forms can be produced by a number of cell types, including epithelial and dendritic cells (DCs. lfTSLP can activate mast cells, DCs, and T cells through binding to the lfTSLP receptor (TSLPR and has a pro-inflammatory function. In contrast, sfTSLP inhibits cytokine secretion of DCs, but the receptor mediating this effect is unknown. Our recent studies have demonstrated that both forms of TSLP display potent antimicrobial activity, exceeding that of many other known antimicrobial peptides (AMPs, with sfTSLP having the strongest effect. The AMP activity is primarily mediated by the C-terminal region of the protein and is localized within a 34-mer peptide (MKK34 that spans the C-terminal α-helical region in TSLP. Fluorescent studies of peptide-treated bacteria, electron microscopy, and liposome leakage models showed that MKK34 exerted membrane-disrupting effects comparable to those of LL-37. Expression of TSLP in skin, oral mucosa, salivary glands, and intestine is part of the defense barrier that aids in the control of both commensal and pathogenic microbes.

  4. Notch-deficient skin induces a lethal systemic B-lymphoproliferative disorder by secreting TSLP, a sentinel for epidermal integrity.

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    Shadmehr Demehri

    2008-05-01

    Full Text Available Epidermal keratinocytes form a highly organized stratified epithelium and sustain a competent barrier function together with dermal and hematopoietic cells. The Notch signaling pathway is a critical regulator of epidermal integrity. Here, we show that keratinocyte-specific deletion of total Notch signaling triggered a severe systemic B-lymphoproliferative disorder, causing death. RBP-j is the DNA binding partner of Notch, but both RBP-j-dependent and independent Notch signaling were necessary for proper epidermal differentiation and lipid deposition. Loss of both pathways caused a persistent defect in skin differentiation/barrier formation. In response, high levels of thymic stromal lymphopoietin (TSLP were released into systemic circulation by Notch-deficient keratinocytes that failed to differentiate, starting in utero. Exposure to high TSLP levels during neonatal hematopoiesis resulted in drastic expansion of peripheral pre- and immature B-lymphocytes, causing B-lymphoproliferative disorder associated with major organ infiltration and subsequent death, a previously unappreciated systemic effect of TSLP. These observations demonstrate that local skin perturbations can drive a lethal systemic disease and have important implications for a wide range of humoral and autoimmune diseases with skin manifestations.

  5. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP) and CCL11/eotaxin-1 in human asthmatic airways.

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    Nino, Gustavo; Huseni, Shehlanoor; Perez, Geovanny F; Pancham, Krishna; Mubeen, Humaira; Abbasi, Aleeza; Wang, Justin; Eng, Stephen; Colberg-Poley, Anamaris M; Pillai, Dinesh K; Rose, Mary C

    2014-01-01

    Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. Our data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  6. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

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    Gustavo Nino

    Full Text Available Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay.Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1.There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  7. Signal transduction around thymic stromal lymphopoietin (TSLP in atopic asthma

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    Kuepper Michael

    2008-08-01

    Full Text Available Abstract Thymic stromal lymphopoietin (TSLP, a novel interleukin-7-like cytokine, triggers dendritic cell-mediated inflammatory responses ultimately executed by T helper cells of the Th2 subtype. TSLP emerged as a central player in the development of allergic symptoms, especially in the airways, and is a prime regulatory cytokine at the interface of virus- or antigen-exposed epithelial cells and dendritic cells (DCs. DCs activated by epithelium-derived TSLP can promote naïve CD4+ T cells to adopt a Th2 phenotype, which in turn recruite eosinophilic and basophilic granulocytes as well as mast cells into the airway mucosa. These different cells secrete inflammatory cytokines and chemokines operative in inducing an allergic inflammation and atopic asthma. TSLP is, thus, involved in the control of both an innate and an adaptive immune response. Since TSLP links contact of allergen with the airway epithelium to the onset and maintainance of the asthmatic syndrome, defining the signal transduction underlying TSLP expression and function is of profound interest for a better understandimg of the disease and for the development of new therapeutics.

  8. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies

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    Masutaka Furue

    2017-07-01

    Full Text Available Atopic dermatitis (AD is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD. Upon activation of the ORAI1 calcium channel, atopic epidermis releases large amounts of thymic stromal lymphopoietin (TSLP, which initiates the Th2 and Th22 immune response. Th2-derived interleukin-31 and TSLP induce an itch sensation. Taken together, TSLP/Th2/Th22 pathway is a promising target for developing new therapeutics for AD. Enhancing filaggrin expression using ligands for the aryl hydrocarbon receptor may also be an adjunctive measure to restore the disrupted barrier function specifically for AD.

  9. Expression analysis and specific blockade of the receptor for human thymic stromal lymphopoietin (TSLP) by novel antibodies to the human TSLPRα receptor chain.

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    Borowski, Andreas; Vetter, Tina; Kuepper, Michael; Wohlmann, Andreas; Krause, Sebastian; Lorenzen, Thomas; Virchow, Johann Christian; Luttmann, Werner; Friedrich, Karlheinz

    2013-02-01

    Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine with a pivotal role in development and maintenance of atopic diseases such as allergic asthma and atopic dermatitis. Moreover, recent studies show an involvement of TSLP in the progression of various cancers. TSLP signaling is mediated by the TSLP receptor (TSLPR), a heterodimeric type I cytokine receptor. It consists of the IL-7 receptor alpha chain (IL-7Rα), which is shared with the IL-7 receptor, and the TSLPRα chain as a specific subunit. Blocking signal release by TSLP without affecting IL-7 function is a potentially interesting option for the treatment of atopic diseases or certain tumors. By employing the extracellular domain of human TSLPRα chain (hTSLPRα(ex)) as an antigen, we generated a set of monoclonal antibodies. Several binders to native and/or denatured receptor protein were identified and characterized by cytometry and Western blot analysis. A screen based on a STAT3-driven reporter gene assay in murine pro-B cells expressing a functional hTSLPR yielded two hybridoma clones with specific antagonistic properties towards hTSLP, but not IL-7. Kinetic studies measuring blockade of hTSLP-dependent STAT phosphorylation in a TSLP-responsive cell line revealed an inhibitory constant in the nanomolar range. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Neutralization of TSLP inhibits airway remodeling in a murine model of allergic asthma induced by chronic exposure to house dust mite.

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    Zhuang-Gui Chen

    Full Text Available Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP, an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1 were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

  11. The Additive Inflammatory In Vivo and In Vitro Effects of IL-7 and TSLP in Arthritis Underscore the Therapeutic Rationale for Dual Blockade.

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    Maarten R Hillen

    Full Text Available The cytokines interleukin (IL-7 and thymic stromal lymphopoietin (TSLP signal through the IL-7R subunit and play proinflammatory roles in experimental arthritis and rheumatoid arthritis (RA. We evaluated the effect of inhibition of IL-7R- and TSLPR-signalling as well as simultaneous inhibition of IL-7R- and TSLPR-signalling in murine experimental arthritis. In addition, the effects of IL-7 and TSLP in human RA dendritic cell (DC/T-cell co-cultures were studied.Arthritis was induced with proteoglycan in wildtype mice (WT and in mice deficient for the TSLP receptor subunit (TSLPR-/-. Both mice genotypes were treated with anti-IL-7R or phosphate buffered saline. Arthritis severity was assessed and local and circulating cytokines were measured. Autologous CD1c-positive DCs and CD4 T-cells were isolated from peripheral blood of RA patients and were co-cultured in the presence of IL-7, TSLP or both and proliferation and cytokine production were assessed.Arthritis severity and immunopathology were decreased in WT mice treated with anti-IL-7R, in TSLPR-/- mice, and the most robustly in TSLPR-/- mice treated with anti-IL-7R. This was associated with strongly decreased levels of IL-17, IL-6 and CD40L. In human DC/T-cell co-cultures, TSLP and IL-7 additively increased T-cell proliferation and production of Th17-associated cytokines, chemokines and tissue destruction factors.TSLP and IL-7 have an additive effect on the production of Th17-cytokines in a human in vitro model, and enhance arthritis in mice linked with enhanced inflammation and immunopathology. As both cytokines signal via the IL-7R, these data urge for IL-7R-targeting to prevent the activity of both cytokines in RA.

  12. The influence of house dust mite sublingual immunotherapy on the TSLP-OX40L signaling pathway in patients with allergic rhinitis.

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    Meng, Qingxiang; Liu, Xiaolong; Li, Peng; He, Long; Xie, Jinghua; Gao, Xionghui; Wu, Xiaozhong; Su, Fang; Liang, Yong

    2016-08-01

    This study aimed to investigate the clinical efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) extract and to examine T helper 2 (Th2)-type immune responses mediated by the thymic stromal lymphopoietin (TSLP-OX40L) signaling pathway in patients with moderate to severe allergic rhinitis (AR) after 12-month HDM SLIT. Forty-six cases of HDM-sensitized patients with persistent AR in southern China were enrolled in this study. Clinical efficacy of SLIT was assessed by determining the individual nasal symptom score (INSS) and total nasal symptom score (TNSS) after 12-month HDM SLIT. Moreover, the TSLP-OX40L signaling pathway was investigated through measurements of TSLP by enzyme-labeled immunosorbent assay (ELISA) and OX40L by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry. After 12 months of HDM SLIT, TNSS and INSS were significantly decreased overall compared with baseline values (p < 0.001). By the end of the 12-month HDM SLIT, TNSS had declined by ∼50% compared with baseline, and the corresponding level of TSLP in nasal lavage decreased significantly (p < 0.05). The level of OX40L messenger RNA (mRNA) in blood was markedly decreased significantly after 12-month HDM SLIT compared with baseline (t = 12.300, p < 0.05). Furthermore, significant decreases in OX40L expression on the surface of peripheral blood mononuclear cells (PBMCs) (t = 13.100, p < 0.05) and OX40L expression on the surface of CD11c+CD86+ cells in PBMCs (t = 9.946, p < 0.05) after 12-month HDM SLIT were observed. HDM SLIT downregulated Th2-type immune responses mediated by the TSLP-OX40L signaling pathway in patients with persistent moderate to severe AR. © 2016 ARS-AAOA, LLC.

  13. Regulation of Tight Junctions in Upper Airway Epithelium

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    Takashi Kojima

    2013-01-01

    Full Text Available The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP, which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

  14. [Distribution of three polymorphisms of the TSLP gen in African-descendent population from San Basilio de Palenque, Colombia].

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    Fang, Luis; Martínez, Beatriz; Marrugo, Javier

    2013-01-01

    Thymic stromal lymphopoietin (TSLP) has been linked as a susceptibility gene for the development of allergic diseases. It is known that the population of Cartagena is a triethnic mix, in which the component of African ancestry was significantly associated with risk of asthma and high total serum IgE levels. This component comes from African slaves brought into the continent and settled in "palenques", one of them is San Basilio de Palenque, in the Colombian Caribbean Coast. To analyze the distribution of single nucleotide polymorphisms (SNP) rs1837253, rs17551370 and rs2289276 located in TSLP gene, in the African-descendent population of San Basilio de Palenque. By real time-PCR and probes TaqMan SNP Genotyping™, we genotyped three polymorphisms in 80 individuals of African-descent aged 5 to 18 years of age. The frequency of the rs1837253 allele T was 41.9%, for the allele A, 14.3% for rs17551370, and 22.5% for the allele T of rs2289276. The rs17551370 and rs2289276 distribution remained in Hardy- Weinberg genetic equilibrium. The allele frequency of each SNP did not show statistically significant differences with those reported for other African and African-descendent populations. The three polymorphisms in the TSLP were present in the sample population of San Basilio de Palenque and its distribution is similar to that reported for African populations and African ancestry in America.

  15. Distribución de tres polimorfismos del gen TSLP en población afrodescendiente de San Basilio de Palenque, Colombia

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    Luis Fang

    2013-06-01

    Full Text Available Introducción. La linfopoyetina tímica del estroma (Thymic Stromal Lymphopoietin, TSLP se ha vinculado como un gen de propensión al desarrollo de enfermedades alérgicas. Se sabe que la población de Cartagena es una mezcla triétnica, en la cual el componente de herencia africana se asoció con el riesgo de asma y altos niveles séricos de IgE total. Este componente provino de esclavos africanos que lograron organizarse en “palenques”, uno de ellos es San Basilio de Palenque, en la Costa Caribe colombiana. Objetivo. Determinar la distribución de los polimorfismos de nucleótido simple (Single Nucleotide Polymorphism, SNP rs1837253, rs17551370 y rs2289276 del gen TSLP en individuos afrodescendientes de San Basilio de Palenque. Materiales y métodos. Mediante PCR en tiempo real y sondas TaqMan SNP Genotyping™ segenotipificaron estos SNP en 80 individuos afrodescendientes entre los 5 y 18 años de edad. Resultados. El alelo de menor frecuencia para el polimorfismo rs1837253 fue el alelo T (41,9 %, para el rs17551370, el alelo A (14,3 %, y para el rs2289276, el alelo T (22,5 %. La distribución de los polimorfismos rs17551370 y rs2289276 se mantuvo en equilibrio genético de Hardy-Weinberg. Las frecuencias alélicas de cada SNP no mostraron diferencias significativas con las reportadas para poblaciones africanas. Conclusiones. Los tres polimorfismos analizados en el gen TSLP estuvieron presentes en la muestra de población de San Basilio de Palenque y su distribución es similar a la reportada para poblaciones africanas y para poblaciones americanas de ancestro africano. doi: http://dx.doi.org/10.7705/biomedica.v33i2.655

  16. BP180 dysfunction triggers spontaneous skin inflammation in mice.

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    Zhang, Yang; Hwang, Bin-Jin; Liu, Zhen; Li, Ning; Lough, Kendall; Williams, Scott E; Chen, Jinbo; Burette, Susan W; Diaz, Luis A; Su, Maureen A; Xiao, Shengxiang; Liu, Zhi

    2018-06-04

    BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic mutations in junctional epidermolysis bullosa (JEB) or autoantibody insult in bullous pemphigoid (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-dysfunctional mouse strain and found that mice lacking functional BP180 (termed Δ NC16A ) developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE levels, and increased expression of thymic stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but dependent on increased expression of TSLP by keratinocytes. In addition, a high TSLP expression is detected in BP patients. Our data provide direct evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and BP180 dysfunction leads to a TSLP-mediated itch. The newly developed mouse strain could be a model for elucidation of disease mechanisms and development of novel therapeutic strategies for skin inflammation and BP180-related skin conditions.

  17. Claudins, dietary milk proteins, and intestinal barrier regulation.

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    Kotler, Belinda M; Kerstetter, Jane E; Insogna, Karl L

    2013-01-01

    The family of claudin proteins plays an important role in regulating the intestinal barrier by modulating the permeability of tight junctions. The impact of dietary protein on claudin biology has not been studied extensively. Whey proteins have been reported to improve intestinal barrier function, but their mechanism of action is not clear. Recent studies, however, have demonstrated increased intestinal claudin expression in response to milk protein components. Reviewed here are new findings suggesting that whey-protein-derived transforming growth factor β transcriptionally upregulates claudin-4 expression via a Smad-4-dependent pathway. These and other data, including limited clinical studies, are summarized below and, in the aggregate, suggest a therapeutic role for whey protein in diseases of intestinal barrier dysfunction, perhaps, in part, by regulating claudin expression. © 2013 International Life Sciences Institute.

  18. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

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    Harmit S. Ranhotra

    2016-07-01

    Full Text Available The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.

  19. Self-regulation of turbulence bursts and transport barriers

    International Nuclear Information System (INIS)

    Floriani, E; Ciraolo, G; Ghendrih, Ph; Sarazin, Y; Lima, R

    2013-01-01

    The interplay between turbulent bursts and transport barriers is analyzed with a simplified model of interchange turbulence in magnetically confined plasmas. The turbulent bursts spread into the transport barriers and, depending on the competing magnitude of the burst and stopping capability of the barrier, can burn through. Simulations of two models of transport barriers are presented: a hard barrier where interchange turbulence modes are stable in a prescribed region and a soft barrier with external plasma biasing. The response of the transport barriers to the non-linear perturbations of the turbulent bursts, addressed in a predator–prey approach, indicates that the barriers monitor an amplification factor of the turbulent bursts, with amplification smaller than one for most bursts and, in some cases, amplification factors that can significantly exceed unity. The weak barriers in corrugated profiles and magnetic structures, as well as the standard barriers, are characterized by these transmission properties, which then regulate the turbulent burst transport properties. The interplays of barriers and turbulent bursts are modeled as competing stochastic processes. For different classes of the probability density function (PDF) of these processes, one can predict the heavy tail properties of the bursts downstream from the barrier, either exponential for a leaky barrier, or with power laws for a tight barrier. The intrinsic probing of the transport barriers by the turbulent bursts thus gives access to the properties of the barriers. The main stochastic variables are the barrier width and the spreading distance of the turbulent bursts within the barrier, together with their level of correlation. One finds that in the case of a barrier with volumetric losses, such as radiation or particle losses as addressed in our present simulations, the stochastic model predicts a leaky behavior with an exponential PDF of escaping turbulent bursts in agreement with the simulation

  20. ΔNp63 controls a TLR3-mediated mechanism that abundantly provides thymic stromal lymphopoietin in atopic dermatitis.

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    Terufumi Kubo

    Full Text Available In the skin lesions of atopic dermatitis (AD, keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP, causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP. Expression of TSLP receptors in skin tissues and keratinocytes was assessed by immunohistochemistry and quantitative RT-PCR, and in vitro studies were also performed to examine the functional relevance of ΔNp63 in the expression of TSLP receptors and the constituting autocrine and/or paracrine pathway of TSLP under the condition of stimuli to innate receptors sensing cell damage. The results showed that normal keratinocytes in the upper epidermis preferentially expressed TSLP receptors and conversely lacked ΔNp63, which has an inhibitory effect on the expression of TSLP receptors. Interestingly, the epidermis of AD lesions was found to abundantly contain keratinocytes with low or undetectable levels of ΔNp63 (ΔNp63(lo/-. Moreover, in the absence of ΔNp63, keratinocytes readily presented TSLP and other cytokines by stimuli through Toll-like receptor 3 (TLR3. Together with the evidence that extrinsic TSLP itself augments TSLP production by keratinocytes without ΔNp63, the results indicate that ΔNp63(lo/- keratinocytes generate TSLP through a putative autocrine and/or paracrine pathway upon TLR3 stimulation within AD lesions, since moieties of damaged cells and pathogens stimulate TLR3.

  1. Barriers to Construction Health and Safety Self-regulation: A Scoping Case of Nigeria

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    Umeokafor Nnedinma

    2017-03-01

    Full Text Available This scoping study builds on the recent uncovering that in terms of health and safety (H&S, the Nigerian construction industry is self-regulated in various forms, not unregulated and that the size of company can further explain H&S self-regulation. Consequently, the barriers identified through literature review were assessed using questionnaires. Analysis of the data collected from construction practitioners in Nigeria shows that ‘economic factors’ mostly explains the barriers to construction H&S self-regulation. This is followed by the ‘ability to self-regulate’ and ‘lack of awareness’. Furthermore, the results show significant differences among small, medium and large construction contractors on seven factors of which include ‘normative case’ factors, ‘H&S is a duty’, ‘H&S is the right thing’ and ‘unfair H&S standards or legislation’. Although a scoping study, the study draws attention to the barriers to construction H&S self-regulation in Nigeria and demonstrates an alternative to state regulation of H&S.

  2. Government regulation of business in a changing institutional barrier

    Directory of Open Access Journals (Sweden)

    Novikova I.

    2013-02-01

    Full Text Available The article examines the domestic experience in government regulation of business in a changing institutional barrier.Compared the degree of economic freedom in Ukraine. The emphasis is on the need to develop a national strategy of institutional development of domestic entrepreneurship.

  3. Sorting Tubules Regulate Blood-Brain Barrier Transcytosis

    Directory of Open Access Journals (Sweden)

    Roberto Villaseñor

    2017-12-01

    Full Text Available Transcytosis across the blood-brain barrier (BBB regulates key processes of the brain, but the intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate intracellular transport in BECs, and we uncovered a pathway for the regulation of receptor-mediated transcytosis. By combining live-cell imaging and mathematical modeling in vitro with super-resolution microscopy of the BBB, we show that intracellular tubules promote transcytosis across the BBB. A monovalent construct (sFab sorted for transcytosis was localized to intracellular tubules, whereas a bivalent construct (dFab sorted for degradation formed clusters with impaired transport along tubules. Manipulating tubule biogenesis by overexpressing the small GTPase Rab17 increased dFab transport into tubules and induced its transcytosis in BECs. We propose that sorting tubules regulate transcytosis in BECs and may be a general mechanism for receptor-mediated transport across the BBB.

  4. [Barriers and opportunities for the regulation of food and beverage advertising to children in Mexico].

    Science.gov (United States)

    Théodore, Florence; Juárez-Ramírez, Clara; Cahuana-Hurtado, Lucero; Blanco, Ilian; Tolentino-Mayo, Lizbeth; Bonvecchio, Anabelle

    2014-01-01

    To identify barriers and opportunities for the regulation of food and beverage advertising to children. A qualitative study. Fourteen key informants from the congress, private sector, officials from the ministry of health and academics involved in the issue of regulation of advertising were interviewed. Barriers identified: conception of obesity as an individual problem, minimization of the negative effects on health, definition of the vulnerability of children bounded to their cognitive development. Facilitators support from various sectors of society regulation, extensive scientific discussion on the subject, successful experience and its lessons on tabacco industry. Mexico has key elements for achieving effective regulation on advertising.

  5. Could tight junctions regulate the barrier function of the aged skin?

    Science.gov (United States)

    Svoboda, Marek; Bílková, Zuzana; Muthný, Tomáš

    2016-03-01

    The skin is known to be the largest organ in human organism creating interface with outer environment. The skin provides protective barrier against pathogens, physical and chemical insults, and against uncontrolled loss of water. The barrier function was primarily attributed to the stratum corneum (SC) but recent studies confirmed that epidermal tight junctions (TJs) also play important role in maintaining barrier properties of the skin. Independent observations indicate that barrier function and its recovery is impaired in aged skin. However, trans-epidermal water loss (TEWL) values remains rather unchanged in elderly population. UV radiation as major factor of photoageing impairs TJ proteins, but TJs have great self-regenerative potential. Since it may be possible that TJs can compensate TEWL in elderly due to its regenerative and compensatory capabilities, important question remains to be answered: how are TJs regulated during skin ageing? This review provides an insight into TJs functioning as epidermal barrier and summarizes current knowledge about the impact of ageing on the barrier function of the skin and epidermal TJs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Targeting allergen to FcgammaRI reveals a novel T(H)2 regulatory pathway linked to thymic stromal lymphopoietin receptor.

    Science.gov (United States)

    Hulse, Kathryn E; Reefer, Amanda J; Engelhard, Victor H; Patrie, James T; Ziegler, Steven F; Chapman, Martin D; Woodfolk, Judith A

    2010-01-01

    The molecule H22-Fel d 1, which targets cat allergen to FcgammaRI on dendritic cells (DCs), has the potential to treat cat allergy because of its T-cell modulatory properties. We sought to investigate whether the T-cell response induced by H22-Fel d 1 is altered in the presence of the T(H)2-promoting cytokine thymic stromal lymphopoietin (TSLP). Studies were performed in subjects with cat allergy with and without atopic dermatitis. Monocyte-derived DCs were primed with H22-Fel d 1 in the presence or absence of TSLP, and the resulting T-cell cytokine repertoire was analyzed by flow cytometry. The capacity for H22-Fel d 1 to modulate TSLP receptor expression on DCs was examined by flow cytometry in the presence or absence of inhibitors of Fc receptor signaling molecules. Surprisingly, TSLP alone was a weak inducer of T(H)2 responses irrespective of atopic status; however, DCs coprimed with TSLP and H22-Fel d 1 selectively and synergistically amplified T(H)2 responses in highly atopic subjects. This effect was OX40 ligand independent, pointing to an unconventional TSLP-mediated pathway. Expression of TSLP receptor was upregulated on atopic DCs primed with H22-Fel d 1 through a pathway regulated by FcgammaRI-associated signaling components, including src-related tyrosine kinases and Syk, as well as the downstream molecule phosphoinositide 3-kinase. Inhibition of TSLP receptor upregulation triggered by H22-Fel d 1 blocked TSLP-mediated T(H)2 responses. Discovery of a novel T(H)2 regulatory pathway linking FcgammaRI signaling to TSLP receptor upregulation and consequent TSLP-mediated effects questions the validity of receptor-targeted allergen vaccines. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  7. Skin barrier homeostasis in atopic dermatitis: feedback regulation of kallikrein activity.

    Directory of Open Access Journals (Sweden)

    Reiko J Tanaka

    Full Text Available Atopic dermatitis (AD is a widely spread cutaneous chronic disease characterised by sensitive reactions (eg. eczema to normally innocuous elements. Although relatively little is understood about its underlying mechanisms due to its complexity, skin barrier dysfunction has been recognised as a key factor in the development of AD. Skin barrier homeostasis requires tight control of the activity of proteases, called kallikreins (KLKs, whose activity is regulated by a complex network of protein interactions that remains poorly understood despite its pathological importance. Characteristic symptoms of AD include the outbreak of inflammation triggered by external (eg. mechanical and chemical stimulus and the persistence and aggravation of inflammation even if the initial stimulus disappears. These characteristic symptoms, together with some experimental data, suggest the presence of positive feedback regulation for KLK activity by inflammatory signals. We developed simple mathematical models for the KLK activation system to study the effects of feedback loops and carried out bifurcation analysis to investigate the model behaviours corresponding to inflammation caused by external stimulus. The model analysis confirmed that the hypothesised core model mechanisms capture the essence of inflammation outbreak by a defective skin barrier. Our models predicted the outbreaks of inflammation at weaker stimulus and its longer persistence in AD patients compared to healthy control. We also proposed a novel quantitative indicator for inflammation level by applying principal component analysis to microarray data. The model analysis reproduced qualitative AD characteristics revealed by this indicator. Our results strongly implicate the presence and importance of feedback mechanisms in KLK activity regulation. We further proposed future experiments that may provide informative data to enhance the system-level understanding on the regulatory mechanisms of skin barrier

  8. Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

    Science.gov (United States)

    Gon, Yasuhiro; Hashimoto, Shu

    2018-01-01

    Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  9. Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

    Directory of Open Access Journals (Sweden)

    Constanza Ballesteros-Martinez

    2017-10-01

    Full Text Available Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1 is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in vascular permeability, causing great loss of intravascular volume in a short time. Nevertheless, the molecular basis remains unexplored on the vascular level. We investigated Rcan1 expression induced by histamine, platelet-activating factor (PAF, and epinephrine in primary human vein (HV-/artery (HA-derived endothelial cells (ECs and human dermal microvascular ECs (HMVEC-D. Vascular permeability was analyzed in vitro in human ECs with forced Rcan1 expression using Transwell migration assays and in vivo using Rcan1 knockout mice. Histamine, but neither PAF nor epinephrine, induced Rcan1-4 mRNA and protein expression in primary HV-ECs, HA-ECs, and HMVEC-D through histamine receptor 1 (H1R. These effects were prevented by pharmacological inhibition of calcineurin with cyclosporine A. Moreover, intravenous histamine administration increased Rcan1 expression in lung tissues of mice undergoing experimental anaphylaxis. Functional in vitro assays showed that overexpression of Rcan1 promotes barrier integrity, suggesting a role played by this molecule in vascular permeability. Consistent with these findings, in vivo models of subcutaneous and intravenous histamine-mediated fluid extravasation showed increased response in skin, aorta, and lungs of Rcan1-deficient mice compared with wild-type animals. These findings reveal that endothelial Rcan1 is synthesized in response to histamine through a calcineurin-sensitive pathway and may reduce barrier breakdown, thus contributing to the strengthening of the endothelium and resistance to anaphylaxis. These new insights underscore its potential role as a regulator of sensitivity to anaphylaxis in humans.

  10. Hydrogen sulfide metabolism regulates endothelial solute barrier function

    Directory of Open Access Journals (Sweden)

    Shuai Yuan

    2016-10-01

    Full Text Available Hydrogen sulfide (H2S is an important gaseous signaling molecule in the cardiovascular system. In addition to free H2S, H2S can be oxidized to polysulfide which can be biologically active. Since the impact of H2S on endothelial solute barrier function is not known, we sought to determine whether H2S and its various metabolites affect endothelial permeability. In vitro permeability was evaluated using albumin flux and transendothelial electrical resistance. Different H2S donors were used to examine the effects of exogenous H2S. To evaluate the role of endogenous H2S, mouse aortic endothelial cells (MAECs were isolated from wild type mice and mice lacking cystathionine γ-lyase (CSE, a predominant source of H2S in endothelial cells. In vivo permeability was evaluated using the Miles assay. We observed that polysulfide donors induced rapid albumin flux across endothelium. Comparatively, free sulfide donors increased permeability only with higher concentrations and at later time points. Increased solute permeability was associated with disruption of endothelial junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress fiber formation. Importantly, sulfide donors that increase permeability elicited a preferential increase in polysulfide levels within endothelium. Similarly, CSE deficient MAECs showed enhanced solute barrier function along with reduced endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial junction structures with increased claudin 5 protein expression. In vivo, CSE genetic deficiency significantly blunted VEGF induced hyperpermeability revealing an important role of the enzyme for barrier function. In summary, endothelial solute permeability is critically regulated via exogenous and endogenous sulfide bioavailability with a prominent role of polysulfides.

  11. Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

    Science.gov (United States)

    Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

    2012-01-01

    Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

  12. Desmoglein 2 regulates the intestinal epithelial barrier via p38 mitogen-activated protein kinase.

    Science.gov (United States)

    Ungewiß, Hanna; Vielmuth, Franziska; Suzuki, Shintaro T; Maiser, Andreas; Harz, Hartmann; Leonhardt, Heinrich; Kugelmann, Daniela; Schlegel, Nicolas; Waschke, Jens

    2017-07-24

    Intestinal epithelial barrier properties are maintained by a junctional complex consisting of tight junctions (TJ), adherens junctions (AJ) and desmosomes. Desmoglein 2 (Dsg2), an adhesion molecule of desmosomes and the only Dsg isoform expressed in enterocytes, is required for epithelial barrier properties and may contribute to barrier defects in Crohn's disease. Here, we identified extradesmosomal Dsg2 on the surface of polarized enterocytes by Triton extraction, confocal microscopy, SIM and STED. Atomic force microscopy (AFM) revealed Dsg2-specific binding events along the cell border on the surface of enterocytes with a mean unbinding force of around 30pN. Binding events were blocked by an inhibitory antibody targeting Dsg2 which under same conditions activated p38MAPK but did not reduce cell cohesion. In enterocytes deficient for Dsg2, p38MAPK activity was reduced and both barrier integrity and reformation were impaired. Dsc2 rescue did not restore p38MAPK activity indicating that Dsg2 is required. Accordingly, direct activation of p38MAPK in Dsg2-deficient cells enhanced barrier reformation demonstrating that Dsg2-mediated activation of p38MAPK is crucial for barrier function. Collectively, our data show that Dsg2, beside its adhesion function, regulates intestinal barrier function via p38MAPK signalling. This is in contrast to keratinocytes and points towards tissue-specific signalling functions of desmosomal cadherins.

  13. Trauma-Induced Heterotopic Ossification Regulates the Blood-Nerve Barrier

    Directory of Open Access Journals (Sweden)

    Zbigniew Gugala

    2018-06-01

    Full Text Available De novo bone formation can occur in soft tissues as a result of traumatic injury. This process, known as heterotopic ossification (HO, has recently been linked to the peripheral nervous system. Studies suggest that HO may resemble neural crest-derived bone formation and is activated through the release of key bone matrix proteins leading to opening of the blood-nerve barrier (BNB. One of the first steps in this process is the activation of a neuro-inflammatory cascade, which results in migration of chondro-osseous progenitors, and other cells from both the endoneurial and perineurial regions of the peripheral nerves. The perineurial cells undergo brown adipogenesis, to form essential support cells, which regulate expression and activation of matrix metallopeptidase 9 (MMP9 an essential regulatory protein involved in opening the BNB. However, recent studies suggest that, in mice, a key bone matrix protein, bone morphogenetic protein 2 (BMP2 is able to immediately cross the BNB to activate signaling in specific cells within the endoneurial compartment. BMP signaling correlates with bone formation and appears critical for the induction of HO. Surprisingly, several other bone matrix proteins have also been reported to regulate the BNB, leading us to question whether these matrix proteins are important in regulating the BNB. However, this temporary regulation of the BNB does not appear to result in degeneration of the peripheral nerve, but rather may represent one of the first steps in innervation of the newly forming bone.

  14. Glyphosate–rich air samples induce IL–33, TSLP and generate IL–13 dependent airway inflammation

    Science.gov (United States)

    Kumar, Sudhir; Khodoun, Marat; Kettleson, Eric M.; McKnight, Christopher; Reponen, Tiina; Grinshpun, Sergey A.; Adhikari, Atin

    2014-01-01

    Several low weight molecules have often been implicated in the induction of occupational asthma. Glyphosate, a small molecule herbicide, is widely used in the world. There is a controversy regarding a role of glyphosate in developing asthma and rhinitis among farmers, the mechanism of which is unexplored. The aim of this study was to explore the mechanisms of glyphosate induced pulmonary pathology by utilizing murine models and real environmental samples. C57BL/6, TLR4−/−, and IL-13−/− mice inhaled extracts of glyphosate-rich air samples collected on farms during spraying of herbicides or inhaled different doses of glyphosate and ovalbumin. The cellular response, humoral response, and lung function of exposed mice were evaluated. Exposure to glyphosate-rich air samples as well as glyphosate alone to the lungs increased: eosinophil and neutrophil counts, mast cell degranulation, and production of IL-33, TSLP, IL-13, and IL-5. In contrast, in vivo systemic IL-4 production was not increased. Co-administration of ovalbumin with glyphosate did not substantially change the inflammatory immune response. However, IL-13-deficiency resulted in diminished inflammatory response but did not have a significant effect on airway resistance upon methacholine challenge after 7 or 21 days of glyphosate exposure. Glyphosate-rich farm air samples as well as glyphosate alone were found to induce pulmonary IL-13-dependent inflammation and promote Th2 type cytokines, but not IL-4 for glyphosate alone. This study, for the first time, provides evidence for the mechanism of glyphosate-induced occupational lung disease. PMID:25172162

  15. "Letting the leaders pass": barriers to using traditional ecological knowledge in comanagement as the basis of formal hunting regulations

    Directory of Open Access Journals (Sweden)

    Elisabeth Padilla

    2014-06-01

    Full Text Available We studied a case of failure in applying traditional ecological knowledge (TEK in comanagement as the basis for formal hunting regulations. We based the study on the Porcupine Caribou (Rangifer tarandus Herd "let the leaders pass" policy, established for the Dempster Highway of the Western Canadian Arctic, and identified conditions creating barriers in the successful application of TEK through comanagement. Stated as propositions, identified barriers include: (1 the context-specific nature of TEK limits its application in resource management regulations; (2 changes in traditional authority systems, hunting technology, and the social organization of harvesting caribou affect the effectiveness of TEK approaches in a contemporary social setting; (3 indigenous efforts toward self-government and political autonomy limit regional comanagement consensus in a heterogeneous cultural landscape; (4 the mismatch of agency enforcement of hunting regulations and TEK-based education is problematic. We analyzed the case through four historical phases of caribou management, complementing the study with a literature review of TEK and wildlife comanagement to explain why TEK integration of caribou leaders in regulatory resource management fell short of success. Identifying and understanding the social dynamics related to these barriers make apparent solutions for transforming the comanagement process.

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

    Directory of Open Access Journals (Sweden)

    Lishi Xie

    Full Text Available 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.

  17. Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery.

    Science.gov (United States)

    Patching, Simon G

    2017-03-01

    Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energy demands of the brain. They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. This article first describes the distribution, function and regulation of glucose transporters at the blood-brain barrier, the major ones being the sodium-independent facilitative transporters GLUT1 and GLUT3. Other GLUTs and sodium-dependent transporters (SGLTs) have also been identified at lower levels and under various physiological conditions. It then considers the effects on glucose transporter expression and distribution of hypoglycemia and hyperglycemia associated with diabetes and oxygen/glucose deprivation associated with cerebral ischemia. A reduction in glucose transporters at the blood-brain barrier that occurs before the onset of the main pathophysiological changes and symptoms of Alzheimer's disease is a potential causative effect in the vascular hypothesis of the disease. Mutations in glucose transporters, notably those identified in GLUT1 deficiency syndrome, and some recreational drug compounds also alter the expression and/or activity of glucose transporters at the blood-brain barrier. Approaches for drug delivery across the blood-brain barrier include the pro-drug strategy whereby drug molecules are conjugated to glucose transporter substrates or encapsulated in nano-enabled delivery systems (e.g. liposomes, micelles, nanoparticles) that are functionalised to target glucose transporters. Finally, the continuous development of blood-brain barrier in vitro models is important for studying glucose transporter function, effects of disease conditions and interactions with drugs and xenobiotics.

  18. Barriers to access to opioid medicines for patients with opioid dependence: a review of legislation and regulations in eleven central and eastern European countries.

    Science.gov (United States)

    Vranken, Marjolein J M; Mantel-Teeuwisse, Aukje K; Jünger, Saskia; Radbruch, Lukas; Scholten, Willem; Lisman, John A; Subataite, Marija; Schutjens, Marie-Hélène D B

    2017-06-01

    Barriers linked to drug control systems are considered to contribute to inequitable access to controlled medicines, leaving millions of people in pain and suffering. Most studies focus on access to opioids for the treatment of severe (cancer) pain. This study aims to identify specific access barriers for patients with opioid dependence in legislation and regulations of 11 central and eastern European countries. This study builds on a previous analysis of legislation and regulations as part of the EU 7th Framework Access To Opioid Medication in Europe (ATOME) project. An in-depth analysis was undertaken to determine specific barriers for patients with opioid dependence in need of opioid analgesics or opioid agonist therapy (OAT). For each country, the number and nature of specific potential barriers for these patients were assessed according to eight categories: prescribing; dispensing; manufacturing; usage; trade and distribution; affordability; penalties; and other. An additional keyword search was conducted to minimize the omission of barriers. Barriers in an additional category, language, were recorded qualitatively. Countries included Bulgaria, Cyprus, Estonia, Greece, Hungary, Latvia, Lithuania, Serbia, Slovakia, Slovenia and Turkey. Ten of the 11 countries (all except Estonia) showed specific potential barriers in their legislation and regulations. The total number of barriers varied from two (Slovenia) to 46 (Lithuania); the number of categories varied from one (Slovenia) to five (Lithuania). Most specific potential barriers were shown in the categories 'prescribing', 'usage' and 'other'. The total number in a single category varied from one to 18 (Lithuania, prescribing). Individual differences between countries in the same specific potential barrier were shown; for example, variation in minimum age criteria for admission to OAT ranging from 15 (Lithuania, in special cases) to 20 years (Greece). All countries had stigmatizing language in their legislation

  19. Driving forces and barriers for environmental technology development; Drivkrefter og barrierer for utvikling av miljoeteknologi

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    Driving forces and barriers behind development and usage of environmental technology is discussed, and also whether there are certain characteristics related to environmental innovations compared to other innovations in general. The development of environmental technology is in principle dominated by the same drivers and barriers as any other technology, but the order and strength of the various factors may be different. This examination as well as other empirical studies shows that regulations play a greater part for environmental technology than 'pure market forces'. To many participants it is important to be one step ahead of the regulations, i.e. the expected regulations are equally important as the factual ones in driving the technology development. Players in the business community express that it is important that the authorities cooperate with them when introducing new regulations. This will increase acceptance for the regulations and facilitate the necessary adjustments. The most important barrier in the development and use of the technologies studied is probably the lack of demand.

  20. Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression

    International Nuclear Information System (INIS)

    Kim, Sung Young; Ryu, Sung Jin; Ahn, Hong Ju; Choi, Hae Ri; Kang, Hyun Tae; Park, Sang Chul

    2010-01-01

    One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hypo-responsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells. Expression levels of several nucleoporins, karyopherin α, karyopherin β, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells.

  1. Senescence-related functional nuclear barrier by down-regulation of nucleo-cytoplasmic trafficking gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Young; Ryu, Sung Jin; Ahn, Hong Ju; Choi, Hae Ri; Kang, Hyun Tae [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of); Park, Sang Chul, E-mail: scpark@snu.ac.kr [Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul 110-799 (Korea, Republic of)

    2010-01-01

    One of the characteristic natures of senescent cells is the hypo- or irresponsiveness not only to growth factors but also to apoptotic stress. In the present study, we confirmed the inhibition of nuclear translocation of activated p-ERK1/2 and NF-kB p50 in response to growth stimuli or LPS in the senescent human diploid fibroblasts. In order to elucidate the underlying mechanism for the senescence-associated hypo-responsiveness, we carried out the comparison study for gene expression profiles through microarray analysis. In consequence, we observed the vast reduction in expression of nucleo-cytoplasmic trafficking genes in senescent cells, when compared with those in young cells. Expression levels of several nucleoporins, karyopherin {alpha}, karyopherin {beta}, Ran, and Ran-regulating factors were confirmed to be down-regulated in senescent HDFs by using RT-PCR and Western blot methods. Taken together, these data suggest the operation of certain senescence-associated functional nuclear barriers by down-regulation of the nucleo-cytoplasmic trafficking genes in the senescent cells.

  2. Control of creatine metabolism by HIF is an endogenous mechanism of barrier regulation in colitis.

    Science.gov (United States)

    Glover, Louise E; Bowers, Brittelle E; Saeedi, Bejan; Ehrentraut, Stefan F; Campbell, Eric L; Bayless, Amanda J; Dobrinskikh, Evgenia; Kendrick, Agnieszka A; Kelly, Caleb J; Burgess, Adrianne; Miller, Lauren; Kominsky, Douglas J; Jedlicka, Paul; Colgan, Sean P

    2013-12-03

    Mucosal surfaces of the lower gastrointestinal tract are subject to frequent, pronounced fluctuations in oxygen tension, particularly during inflammation. Adaptive responses to hypoxia are orchestrated largely by the hypoxia-inducible transcription factors (HIFs). As HIF-1α and HIF-2α are coexpressed in mucosal epithelia that constitute the barrier between the lumen and the underlying immune milieu, we sought to define the discrete contribution of HIF-1 and HIF-2 transactivation pathways to intestinal epithelial cell homeostasis. The present study identifies creatine kinases (CKs), key metabolic enzymes for rapid ATP generation via the phosphocreatine-creatine kinase (PCr/CK) system, as a unique gene family that is coordinately regulated by HIF. Cytosolic CKs are expressed in a HIF-2-dependent manner in vitro and localize to apical intestinal epithelial cell adherens junctions, where they are critical for junction assembly and epithelial integrity. Supplementation with dietary creatine markedly ameliorated both disease severity and inflammatory responses in colitis models. Further, enzymes of the PCr/CK metabolic shuttle demonstrate dysregulated mucosal expression in a subset of ulcerative colitis and Crohn disease patients. These findings establish a role for HIF-regulated CK in epithelial homeostasis and reveal a fundamental link between cellular bioenergetics and mucosal barrier.

  3. Single blinded, randomized, placebo-controlled study on the effects of ciclosporin on cutaneous barrier function and immunological response in atopic beagles.

    Science.gov (United States)

    White, Amelia G; Santoro, Domenico; Ahrens, Kim; Marsella, Rosanna

    2018-03-01

    Ciclosporin (CsA) is a common treatment for canine atopic dermatitis (cAD). cAD is a very common skin disease with a multifactorial pathogenesis due to complex interactions between the host and the environment. The purpose of this study was to describe the physical and immunological effects of CsA in cAD using a canine model of AD. Fourteen beagles were enrolled; seven received CsA orally every 24 h for 28 days, and seven received placebo. All dogs were exposed to relevant allergens, house dust mite solution, one day prior to treatment and once weekly thereafter for 28 consecutive days. Canine atopic dermatitis extent and severity index-03 (CADESI-03) and skin biopsies were performed on day 0, 14, and 28. Quantitative RT-PCR was used to determine levels of cutaneous cytokines and barrier function markers. Indirect immunofluorescence was used to determine protein expression and distribution of nuclear messengers, barrier function and inflammatory [thymic stromal lymphopoietin (TSLP)] markers. The data were tested for normality and then the upaired two samples Student's t-test and the repeated measurements ANOVA, followed by the Dunnett's Multiple Comparison Test as post-hoc analysis, were performed. A P value of immunologic milieu or barrier markers despite evident improvement of physical signs in the treatment group. Although this study confirmed the usefulness of CsA for the treatment of cAD, a clear involvement of CsA on some of the currently known immunological alterations present in cAD was not determined. However, it is important to note that there was no measurable exacerbation of skin barrier dysfunction secondary to CsA administration in this model. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. PPAR-α, a lipid-sensing transcription factor, regulates blood-brain barrier efflux transporter expression.

    Science.gov (United States)

    More, Vijay R; Campos, Christopher R; Evans, Rebecca A; Oliver, Keith D; Chan, Gary Ny; Miller, David S; Cannon, Ronald E

    2017-04-01

    Lipid sensor peroxisome proliferator-activated receptor alpha (PPAR- α) is the master regulator of lipid metabolism. Dietary release of endogenous free fatty acids, fibrates, and certain persistent environmental pollutants, e.g. perfluoroalkyl fire-fighting foam components, are peroxisome proliferator-activated receptor alpha ligands. Here, we define a role for peroxisome proliferator-activated receptor alpha in regulating the expression of three ATP-driven drug efflux transporters at the rat and mouse blood-brain barriers: P-glycoprotein (Abcb1), breast cancer resistance protein (Bcrp/Abcg2), and multidrug resistance-associated protein 2 (Mrp2/Abcc2). Exposing isolated rat brain capillaries to linoleic acid, clofibrate, or PKAs increased the transport activity and protein expression of the three ABC transporters. These effects were blocked by the PPAR- α antagonist, GW6471. Dosing rats with 20 mg/kg or 200 mg/kg of clofibrate decreased the brain accumulation of the P-glycoprotein substrate, verapamil, by 50% (in situ brain perfusion; effects blocked by GW6471) and increased P-glycoprotein expression and activity in capillaries ex vivo. Fasting C57Bl/6 wild-type mice for 24 h increased both serum lipids and brain capillary P-glycoprotein transport activity. Fasting did not alter P-glycoprotein activity in PPAR- α knockout mice. These results indicate that hyperlipidemia, lipid-lowering fibrates and exposure to certain fire-fighting foam components activate blood-brain barrier peroxisome proliferator-activated receptor alpha, increase drug efflux transporter expression and reduce drug delivery to the brain.

  5. Barrier performance researches for the safety evaluation

    International Nuclear Information System (INIS)

    Niibori, Yuichi

    2004-01-01

    So far, many researches were conducted to propose a scientific evidence (a safety case) for the realization of geological disposal in Japan. In order to regulate the geological disposal system of radioactive wastes, on the other hand, we need also a holistic approach to integrate various data related for the performance evaluations of the engineered barrier system and the natural barrier system. However, the scientific bases are not sufficient to establish the safety regulation for such a natural system. For example, we often apply the specific probability density function (PDF) to the uncertainty of barrier system due to the essential heterogeneity. However, the applicability is not clear in the regulation point of view. A viewpoint to understand such an applicability of PDFs has been presented. (author)

  6. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  7. LINFOPOYETINA ESTROMAL TÍMICA: REGULACIÓN DE LA RESPUESTA INMUNE Y LA ENFERMEDAD ALÉRGICA

    Directory of Open Access Journals (Sweden)

    A. Cuéllar

    2007-06-01

    Full Text Available Recientemente se ha descrito una citocina similar a interleucina (IL 7: Thymic Stromal Lymphopoietin (TSLP. La molécula TSLP es secretada por células epiteliales y en humanos estimula principalmente células de linaje mieloide, a diferencia del ratón donde el efecto ocurre en células linfoides. En humanos, TSLP se comporta como un activador potente de células dendríticas inmaduras de linaje mieloide y su actividad biológica varía en los diferentes nichos inmunológicos. Células dendríticas periféricas condicionadas con TSLP atraen células efectoras de la respuesta alérgica. Consistente con estos hallazgos, se ha mostrado que la piel afectada de pacientes con dermatitis atópica es positiva para la expresión de TSLP, sugiriendo que TSLP es una molécula clave en la inflamación alérgica.

  8. Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

    International Nuclear Information System (INIS)

    Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.; Parkos, Charles A.; Nusrat, Asma

    2010-01-01

    The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors or siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.

  9. Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

    Energy Technology Data Exchange (ETDEWEB)

    Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.; Parkos, Charles A. [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States); Nusrat, Asma, E-mail: anusrat@emory.edu [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States)

    2010-07-02

    The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors or siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.

  10. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases.

    Science.gov (United States)

    Sturgeon, Craig; Fasano, Alessio

    2016-01-01

    Beside digesting nutrients and absorbing solutes and electrolytes, the intestinal epithelium with its barrier function is in charge of a tightly controlled antigen trafficking from the intestinal lumen to the submucosa. This trafficking dictates the delicate balance between tolerance and immune response causing inflammation. Loss of barrier function secondary to upregulation of zonulin, the only known physiological modulator of intercellular tight junctions, leads to uncontrolled influx of dietary and microbial antigens. Additional insights on zonulin mechanism of action and the recent appreciation of the role that altered intestinal permeability can play in the development and progression of chronic inflammatory disorders has increased interest of both basic scientists and clinicians on the potential role of zonulin in the pathogenesis of these diseases. This review focuses on the recent research implicating zonulin as a master regulator of intestinal permeability linked to the development of several chronic inflammatory disorders.

  11. Driving forces and barriers for environmental technology development

    International Nuclear Information System (INIS)

    2005-01-01

    Driving forces and barriers behind development and usage of environmental technology is discussed, and also whether there are certain characteristics related to environmental innovations compared to other innovations in general. The development of environmental technology is in principle dominated by the same drivers and barriers as any other technology, but the order and strength of the various factors may be different. This examination as well as other empirical studies shows that regulations play a greater part for environmental technology than 'pure market forces'. To many participants it is important to be one step ahead of the regulations, i.e. the expected regulations are equally important as the factual ones in driving the technology development. Players in the business community express that it is important that the authorities cooperate with them when introducing new regulations. This will increase acceptance for the regulations and facilitate the necessary adjustments. The most important barrier in the development and use of the technologies studied is probably the lack of demand

  12. MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.

    Directory of Open Access Journals (Sweden)

    Victor Chatterjee

    Full Text Available A disintegrin and metalloproteinase15 (ADAM15 has been shown to be upregulated and mediate endothelial hyperpermeability during inflammation and sepsis. This molecule contains multiple functional domains with the ability to modulate diverse cellular processes including cell adhesion, extracellular matrix degradation, and ectodomain shedding of transmembrane proteins. These characteristics make ADAM15 an attractive therapeutic target in various diseases. The lack of pharmacological inhibitors specific to ADAM15 prompted our efforts to identify biological or molecular tools to alter its expression for further studying its function and therapeutic implications. The goal of this study was to determine if ADAM15-targeting microRNAs altered ADAM15-induced endothelial barrier dysfunction during septic challenge by bacterial lipopolysaccharide (LPS. An in silico analysis followed by luciferase reporter assay in human vascular endothelial cells identified miR-147b with the ability to target the 3' UTR of ADAM15. Transfection with a miR-147b mimic led to decreased total, as well as cell surface expression of ADAM15 in endothelial cells, while miR-147b antagomir produced an opposite effect. Functionally, LPS-induced endothelial barrier dysfunction, evidenced by a reduction in transendothelial electric resistance and increase in albumin flux across endothelial monolayers, was attenuated in cells treated with miR-147b mimics. In contrast, miR-147b antagomir exerted a permeability-increasing effect in vascular endothelial cells similar to that caused by LPS. Taken together, these data suggest the potential role of miR147b in regulating endothelial barrier function by targeting ADAM15 expression.

  13. A novel role for inhibitor of apoptosis (IAP) proteins as regulators of endothelial barrier function by mediating RhoA activation.

    Science.gov (United States)

    Hornburger, Michael C; Mayer, Bettina A; Leonhardt, Stefanie; Willer, Elisabeth A; Zahler, Stefan; Beyerle, Andrea; Rajalingam, Krishnaraj; Vollmar, Angelika M; Fürst, Robert

    2014-04-01

    Inhibitor of apoptosis (IAP) proteins, such as XIAP or cIAP1/2, are important regulators of apoptosis in cancer cells, and IAP antagonists are currently evaluated as antitumor agents. Beyond their function in cancer cells, this study demonstrates a novel role of IAPs as regulators of vascular endothelial permeability. Two structurally different IAP antagonists, ABT and Smac085, as well as silencing of IAPs, reduced the thrombin receptor-activating peptide (TRAP)-induced barrier dysfunction in human endothelial cells as assessed by measuring macromolecular permeability or transendothelial electrical resistance. ABT diminished thrombin-evoked stress fiber formation, activation of myosin light chain 2, and disassembly of adherens junctions independent of calcium signaling, protein kinase C, and mitogen-activated protein kinases. Interestingly, ABT and silencing of IAPs, in particular XIAP, reduced the TRAP-evoked RhoA activation, whereas Rac1 was not affected. XIAP and, to a lesser extent, cIAP1 were found to directly interact with RhoA independently of the RhoA activation status. Under cell-free conditions, XIAP did not induce an ubiquitination of RhoA. In summary, our work discloses IAPs as crucial regulators of endothelial permeability and suggests IAP inhibition as interesting approach for the prevention of endothelial barrier dysfunction.

  14. Cloning of rat thymic stromal lymphopoietin receptor (TSLPR) and characterization of genomic structure of murine Tslpr gene

    DEFF Research Database (Denmark)

    Blagoev, Blagoy; Nielsen, Mogens M; Angrist, Misha

    2002-01-01

    , a cytokine involved in B- and T-cell function. We have cloned the TSLP receptor from rat and find that the WSXWX motif commonly found in extracellular domains of cytokine receptors is conserved as a W(T/S)XV(T/A) motif among TSLP receptors from mouse, rat and human. As in the mouse, TSLP receptor is widely...

  15. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer.

    Science.gov (United States)

    Fasano, Alessio

    2011-01-01

    The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a "leaky gut" in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

  16. Lipopolysaccharide attenuates induction of pro-allergic cytokines, thymic stromal lymphopoietin and interleukin 33, in respiratory epithelial cells stimulated with polyI:C and human parechovirus

    Directory of Open Access Journals (Sweden)

    Tsang-Hsiung Lin

    2016-10-01

    Full Text Available Epidemiological studies based on the hygiene hypothesis declare that the level of childhood exposure to environmental microbial products is inversely related to the incidence of allergic diseases in later life. Multiple types of immune cell-mediated immune regulation networks support the hygiene hypothesis. Epithelial cells are the first line of response to microbial products in the environment and bridge the innate and adaptive immune systems; however, their role in the hygiene hypothesis is unknown. To demonstrate the hygiene hypothesis in airway epithelial cells, we examined the effect of lipopolysaccharide (LPS; Toll-like receptor 4 ligand on the expression of the proallergic cytokines thymic stromal lymphopoietin (TSLP and interleukin 33 (IL33 in H292 cells (pulmonary mucoepidermoid carcinoma cells. Stimulation with the TLR ligand polyI:C and human parechovirus type 1 (HPeV1 but not LPS induced TSLP and IL33 through interferon (IFN regulatory factor 3 (IRF3 and NFB activity, which was further validated by using inhibitors (dexamethasone and Bay 11-7082 and shRNA-mediated gene knockdown. Importantly, polyI:C and HPeV1-stimulated TSLP and IL33 induction was reduced by LPS treatment by attenuating TANK-binding kinase 1, IRF3 and NFB activation. Interestingly, the basal mRNA levels of TLR signaling proteins were downregulated with long-term LPS treatment of H292 cells, which suggests that such long-term exposure modulates the expression of innate immunity signaling molecules in airway epithelial cells to mitigate the allergic response. In contrast to the effects of LPS treatment, the alarmin HMBG1 (high mobility group protein B1 acts in synergy with polyI:C to promote TSLP and IL33 expression. Our data support part of the hygiene hypothesis in airway epithelia cells in vitro. In addition to therapeutic targeting of TSLP and IL33, local application of non-pathogenic LPS may be a rational strategy to prevent allergies.

  17. Atomistic modeling of the structural components of the blood-brain barrier

    Science.gov (United States)

    Glukhova, O. E.; Grishina, O. A.; Slepchenkov, M. M.

    2015-03-01

    Blood-brain barrier, which is a barrage system between the brain and blood vessels, plays a key role in the "isolation" of the brain of unnecessary information, and reduce the "noise" in the interneuron communication. It is known that the barrier function of the BBB strictly depends on the initial state of the organism and changes significantly with age and, especially in developing the "vascular accidents". Disclosure mechanisms of regulation of the barrier function will develop new ways to deliver neurotrophic drugs to the brain in the newborn. The aim of this work is the construction of atomistic models of structural components of the blood-brain barrier to reveal the mechanisms of regulation of the barrier function.

  18. Thymic Stromal Lymphopoietin Attenuates the Development of Atherosclerosis in ApoE−/− Mice

    Science.gov (United States)

    Yu, Kunwu; Zhu, Pengfei; Dong, Qian; Zhong, Yucheng; Zhu, Zhengfeng; Lin, Yingzhong; Huang, Ying; Meng, Kai; Ji, Qingwei; Yi, Guiwen; Zhang, Wei; Wu, Bangwei; Mao, Yi; Cheng, Peng; Zhao, Xiaoqi; Mao, Xiaobo; Zeng, Qiutang

    2013-01-01

    Background Thymic stromal lymphopoietin (TSLP) is a cytokine with multiple effects on the body. For one thing, TSLP induces Th2 immunoreaction and facilitates allergic reaction; for another, it promotes the differentiation of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and maintains immune tolerance. However, the exact role of TSLP in atherosclerosis remains unknown. Methods and Results In vitro, we examined the phenotype of TSLP‐conditioned bone marrow dendritic cells (TSLP‐DCs) of apolipoprotein E–deficient (ApoE−/−) mice and their capacity to induce the differentiation of Tregs. Our results indicated that TSLP‐DCs obtained the characteristics of tolerogenic dendritic cells and increased a generation of CD4+ latency‐associated peptide (LAP)+ Tregs and nTregs when cocultured with naive T cells. In addition, the functional relevance of TSLP and TSLP‐DCs in the development of atherosclerosis was also determined. Interestingly, we found that TSLP was almost absent in cardiovascular tissue of ApoE−/− mice, and TSLP administration increased the levels of antioxidized low‐density lipoprotein IgM and IgG1, but decreased the levels of IgG2a in plasma. Furthermore, mice treated with TSLP and TSLP‐DCs developed significantly fewer (32.6% and 28.2%, respectively) atherosclerotic plaques in the aortic root compared with controls, along with increased numbers of CD4+LAP+ Tregs and nTregs in the spleen and decreased inflammation in the aorta, which could be abrogated by anti‐TGF‐β antibody. Conclusions Our results revealed a protective role for TSLP in atherosclerosis that is possibly mediated by reestablishing a tolerogenic immune response, which may represent a novel possibility for treatment or prevention of atherosclerosis. PMID:23985377

  19. Barriers for the introduction of bioenergy in the Netherlands

    International Nuclear Information System (INIS)

    Gerlagh, T.; Groenendaal, B.; Van Ree, R.; Dinkelbach, L.; Van Doorn, J.; Hemmes, K.

    2000-01-01

    The use of biomass for energy in the Netherlands is still limited despite the political incentives to make bio-energy a major source of renewable energy. The hesitation of many stake-holders is due to the limited insight into the potential of biomass in the Netherlands and the presence of numerous other barriers. Availability of biomass, emission regulation and waste treatment regulations are considered important barriers. Analyses of their current state show that these barriers are broadly recognised and possibilities to decrease their impact are present. Some barriers with a minor influence so far will be of increasing importance and could be a threat to the development of bio-energy in future. These are the fast liberalising of the energy market and sustainable energy market, the competition with other renewables and the unclear status of the current technology available. Future research should focus on the possibilities to overcome these new barriers. 5 refs

  20. Barriers in EU retail financial markets

    OpenAIRE

    Micuda, Dan

    2007-01-01

    Looking at the retail financial markets and identifing a number of ‘‘natural’’ and ‘‘policy induced’’ obstacles to free trade. We use the term ‘‘natural’’ barriers to refer to those arising as a result of different cultures or consumer preferences, while different state tax policies or regulations are classified as ‘‘policy induced’’ barriers.

  1. Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin

    DEFF Research Database (Denmark)

    Gelpi, Marco; Hartling, Hans J; Thorsteinsson, Kristina

    2016-01-01

    was comparable in all groups, and no differences in immune homeostasis were found between primary HIV infection and early presenters, whereas differences in absolute counts and proportions of CD4+ T cell subpopulations were found between primary HIV infection and late presenters. TSLP was elevated in primary HIV...... thymic output, but not with immune recovery. These findings indicate a possible role of TSLP in immune homeostasis in HIV infection but do not support TSLP to affect immune recovery in primary HIV infection.......BACKGROUND: Symptomatic primary HIV infection is associated with an adverse prognosis, and immediate initiation of combination antiretroviral therapy (cART) is recommended. However, little is known about immunological predictors of immune recovery. Thymic Stromal Lymphopoietin (TSLP) is a cytokine...

  2. Abl family kinases regulate endothelial barrier function in vitro and in mice.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Chislock

    Full Text Available The maintenance of endothelial barrier function is essential for normal physiology, and increased vascular permeability is a feature of a wide variety of pathological conditions, leading to complications including edema and tissue damage. Use of the pharmacological inhibitor imatinib, which targets the Abl family of non-receptor tyrosine kinases (Abl and Arg, as well as other tyrosine kinases including the platelet-derived growth factor receptor (PDGFR, Kit, colony stimulating factor 1 receptor (CSF1R, and discoidin domain receptors, has shown protective effects in animal models of inflammation, sepsis, and other pathologies characterized by enhanced vascular permeability. However, the imatinib targets involved in modulation of vascular permeability have not been well-characterized, as imatinib inhibits multiple tyrosine kinases not only in endothelial cells and pericytes but also immune cells important for disorders associated with pathological inflammation and abnormal vascular permeability. In this work we employ endothelial Abl knockout mice to show for the first time a direct role for Abl in the regulation of vascular permeability in vivo. Using both Abl/Arg-specific pharmacological inhibition and endothelial Abl knockout mice, we demonstrate a requirement for Abl kinase activity in the induction of endothelial permeability by vascular endothelial growth factor both in vitro and in vivo. Notably, Abl kinase inhibition also impaired endothelial permeability in response to the inflammatory mediators thrombin and histamine. Mechanistically, we show that loss of Abl kinase activity was accompanied by activation of the barrier-stabilizing GTPases Rac1 and Rap1, as well as inhibition of agonist-induced Ca(2+ mobilization and generation of acto-myosin contractility. In all, these findings suggest that pharmacological targeting of the Abl kinases may be capable of inhibiting endothelial permeability induced by a broad range of agonists and that use

  3. An analysis of potential barriers and enablers to regulating the television marketing of unhealthy foods to children at the state government level in Australia.

    Science.gov (United States)

    Chung, Alexandra; Shill, Jane; Swinburn, Boyd; Mavoa, Helen; Lawrence, Mark; Loff, Bebe; Crammond, Bradley; Sacks, Gary; Allender, Steven; Peeters, Anna

    2012-12-28

    In Australia there have been many calls for government action to halt the effects of unhealthy food marketing on children's health, yet implementation has not occurred. The attitudes of those involved in the policy-making process towards regulatory intervention governing unhealthy food marketing are not well understood. The objective of this research was to understand the perceptions of senior representatives from Australian state and territory governments, statutory authorities and non-government organisations regarding the feasibility of state-level government regulation of television marketing of unhealthy food to children in Australia. Data from in-depth semi-structured interviews with senior representatives from state and territory government departments, statutory authorities and non-government organisations (n=22) were analysed to determine participants' views about regulation of television marketing of unhealthy food to children at the state government level. Data were analysed using content and thematic analyses. Regulation of television marketing of unhealthy food to children was supported as a strategy for obesity prevention. Barriers to implementing regulation at the state level were: the perception that regulation of television advertising is a Commonwealth, not state/territory, responsibility; the power of the food industry and; the need for clear evidence that demonstrates the effectiveness of regulation. Evidence of community support for regulation was also cited as an important factor in determining feasibility. The regulation of unhealthy food marketing to children is perceived to be a feasible strategy for obesity prevention however barriers to implementation at the state level exist. Those involved in state-level policy making generally indicated a preference for Commonwealth-led regulation. This research suggests that implementation of regulation of the television marketing of unhealthy food to children should ideally occur under the direction

  4. An analysis of potential barriers and enablers to regulating the television marketing of unhealthy foods to children at the state government level in Australia

    Directory of Open Access Journals (Sweden)

    Chung Alexandra

    2012-12-01

    Full Text Available Abstract Background In Australia there have been many calls for government action to halt the effects of unhealthy food marketing on children's health, yet implementation has not occurred. The attitudes of those involved in the policy-making process towards regulatory intervention governing unhealthy food marketing are not well understood. The objective of this research was to understand the perceptions of senior representatives from Australian state and territory governments, statutory authorities and non-government organisations regarding the feasibility of state-level government regulation of television marketing of unhealthy food to children in Australia. Method Data from in-depth semi-structured interviews with senior representatives from state and territory government departments, statutory authorities and non-government organisations (n=22 were analysed to determine participants' views about regulation of television marketing of unhealthy food to children at the state government level. Data were analysed using content and thematic analyses. Results Regulation of television marketing of unhealthy food to children was supported as a strategy for obesity prevention. Barriers to implementing regulation at the state level were: the perception that regulation of television advertising is a Commonwealth, not state/territory, responsibility; the power of the food industry and; the need for clear evidence that demonstrates the effectiveness of regulation. Evidence of community support for regulation was also cited as an important factor in determining feasibility. Conclusions The regulation of unhealthy food marketing to children is perceived to be a feasible strategy for obesity prevention however barriers to implementation at the state level exist. Those involved in state-level policy making generally indicated a preference for Commonwealth-led regulation. This research suggests that implementation of regulation of the television marketing of

  5. ROS-activated calcium signaling mechanisms regulating endothelial barrier function.

    Science.gov (United States)

    Di, Anke; Mehta, Dolly; Malik, Asrar B

    2016-09-01

    Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults

    DEFF Research Database (Denmark)

    Bjerregaard, Asger; Laing, Ingrid A; Poulsen, Nadia

    2017-01-01

    BACKGROUND: In experimental studies viral infections have been shown to induce type 2 inflammation in asthmatics, but whether this is a feature of naturally occurring virus-induced asthma exacerbations is unknown. Thymic stromal lymphopoietin (TSLP) released from the airway epithelium in response...... occurring virus-induced exacerbations of asthma and whether TSLP is associated with this type 2 inflammation. METHODS: Patients presenting to hospital with acute asthma were examined during the exacerbation, and after 4 weeks recovery. The assessments included spirometry, FeNO and induced sputum...... in patients during virus-induced asthma exacerbations, to the same degree as non-viral exacerbations, and correlate negatively with FEV1. However, in virus-positive patients, high TSLP expression during exacerbation was associated with low sputum eosinophils, suggesting that the effect of TSLP in vivo...

  7. Herbal medicines that benefit epidermal permeability barrier function

    Directory of Open Access Journals (Sweden)

    Lizhi Hu

    2015-06-01

    Full Text Available Epidermal permeability barrier function plays a critical role in regulating cutaneous functions. Hence, researchers have been searching for effective and affordable regimens to enhance epidermal permeability barrier function. In addition to topical stratum corneum lipids, peroxisome proliferator-activated receptor, and liver X receptor ligands, herbal medicines have been proven to benefit epidermal permeability barrier function in both normal and diseased skin, including atopic dermatitis, glucocorticoid-induced skin damage, and UVB-damaged skin. The potential mechanisms by which herbal medicines improve the permeability barrier include stimulation of epidermal differentiation, lipid production, antimicrobial peptide expression, and antioxidation. Therefore, utilization of herbal medicines could be a valuable alternative approach to enhance epidermal permeability barrier function in order to prevent and/or treat skin disorders associated with permeability barrier abnormalities.

  8. The potential protective role of taurine against experimental allergic inflammation.

    Science.gov (United States)

    Nam, Sun-Young; Kim, Hyung-Min; Jeong, Hyun-Ja

    2017-09-01

    Taurine has been widely evaluated as a potential therapeutic agent in chronic inflammatory disorders and various infections. However, the potential role of taurine in regulating allergic inflammatory responses is currently unknown. The present study was designed to evaluate the in vitro effects of taurine on the levels of thymic stromal lymphopoietin (TSLP) and other pro-inflammatory cytokines and activation of caspase-1 and nuclear factor (NF)-κB as well as the phosphorylations of c-Jun N-terminal kinase (JNK) and p38 in phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-triggered human mast cell line, HMC-1 cells. Furthermore, we assessed the therapeutic effects of taurine on ovalbumin (OVA)-induced allergic rhinitis (AR) animal models. Here, the obtained results showed that taurine dose-dependently inhibited the production and mRNA expression of TSLP and pro-inflammatory cytokines in HMC-1 cells exposed to PMACI. Taurine attenuated the phosphorylation of JNK and p38 in activated HMC-1 cells. Moreover, taurine brought a significant inhibition of the activities of NF-κB and caspase-1. In an OVA-induced AR animal model, the increased levels of nose rubbing, histamine, immunoglobulin E, TSLP, and interleukin IL-1β were dramatically reduced by the administration of taurine. In summary, taurine could serve as potential novel remedy of allergic inflammatory disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The long noncoding RNA TUG1 regulates blood-tumor barrier permeability by targeting miR-144.

    Science.gov (United States)

    Cai, Heng; Xue, Yixue; Wang, Ping; Wang, Zhenhua; Li, Zhen; Hu, Yi; Li, Zhiqing; Shang, Xiuli; Liu, Yunhui

    2015-08-14

    Blood-tumor barrier (BTB) limits the delivery of chemotherapeutic agent to brain tumor tissues. Long non-coding RNAs (lncRNAs) have been shown to play critical regulatory roles in various biologic processes of tumors. However, the role of lncRNAs in BTB permeability is unclear. LncRNA TUG1 (taurine upregulated gene 1) was highly expressed in glioma vascular endothelial cells from glioma tissues. It also upregulated in glioma co-cultured endothelial cells (GEC) from BTB model in vitro. Knockdown of TUG1 increased BTB permeability, and meanwhile down-regulated the expression of the tight junction proteins ZO-1, occludin, and claudin-5. Both bioinformatics and luciferase reporter assays demonstrated that TUG1 influenced BTB permeability via binding to miR-144. Furthermore, Knockdown of TUG1 also down-regulated Heat shock transcription factor 2 (HSF2), a transcription factor of the heat shock transcription factor family, which was defined as a direct and functional downstream target of miR-144. HSF2 up-regulated the promoter activities and interacted with the promoters of ZO-1, occludin, and claudin-5 in GECs. In conclusion, our results indicate that knockdown of TUG1 increased BTB permeability via binding to miR-144 and then reducing EC tight junction protein expression by targeting HSF2. Thus, TUG1 may represent a useful future therapeutic target for enhancing BTB permeability.

  10. Barrier properties of cultured retinal pigment epithelium.

    Science.gov (United States)

    Rizzolo, Lawrence J

    2014-09-01

    The principal function of an epithelium is to form a dynamic barrier that regulates movement between body compartments. Each epithelium is specialized with barrier functions that are specific for the tissues it serves. The apical surface commonly faces a lumen, but the retinal pigment epithelium (RPE) appears to be unique by a facing solid tissue, the sensory retina. Nonetheless, there exists a thin (subretinal) space that can become fluid filled during pathology. RPE separates the subretinal space from the blood supply of the outer retina, thereby forming the outer blood-retinal barrier. The intricate interaction between the RPE and sensory retina presents challenges for learning how accurately culture models reflect native behavior. The challenge is heightened by findings that detail the variation of RPE barrier proteins both among species and at different stages of the life cycle. Among the striking differences is the expression of claudin family members. Claudins are the tight junction proteins that regulate ion diffusion across the spaces that lie between the cells of a monolayer. Claudin expression by RPE varies with species and life-stage, which implies functional differences among commonly used animal models. Investigators have turned to transcriptomics to supplement functional studies when comparing native and cultured tissue. The most detailed studies of the outer blood-retinal barrier have focused on human RPE with transcriptome and functional studies reported for human fetal, adult, and stem-cell derived RPE. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Sphingosine 1-Phosphate (S1P) Carrier-dependent Regulation of Endothelial Barrier

    Science.gov (United States)

    Wilkerson, Brent A.; Grass, G. Daniel; Wing, Shane B.; Argraves, W. Scott; Argraves, Kelley M.

    2012-01-01

    Sphingosine 1-phosphate (S1P) is a blood-borne lysosphingolipid that acts to promote endothelial cell (EC) barrier function. In plasma, S1P is associated with both high density lipoproteins (HDL) and albumin, but it is not known whether the carriers impart different effects on S1P signaling. Here we establish that HDL-S1P sustains EC barrier longer than albumin-S1P. We showed that the sustained barrier effects of HDL-S1P are dependent on signaling by the S1P receptor, S1P1, and involve persistent activation of Akt and endothelial NOS (eNOS), as well as activity of the downstream NO target, soluble guanylate cyclase (sGC). Total S1P1 protein levels were found to be higher in response to HDL-S1P treatment as compared with albumin-S1P, and this effect was not associated with increased S1P1 mRNA or dependent on de novo protein synthesis. Several pieces of evidence indicate that long term EC barrier enhancement activity of HDL-S1P is due to specific effects on S1P1 trafficking. First, the rate of S1P1 degradation, which is proteasome-mediated, was slower in HDL-S1P-treated cells as compared with cells treated with albumin-S1P. Second, the long term barrier-promoting effects of HDL-S1P were abrogated by treatment with the recycling blocker, monensin. Finally, cell surface levels of S1P1 and levels of S1P1 in caveolin-enriched microdomains were higher after treatment with HDL-S1P as compared with albumin-S1P. Together, the findings reveal S1P carrier-specific effects on S1P1 and point to HDL as the physiological mediator of sustained S1P1-PI3K-Akt-eNOS-sGC-dependent EC barrier function. PMID:23135269

  12. Genes Linked to Endometriosis by GWAS Are Integral to Cytoskeleton Regulation and Suggests That Mesothelial Barrier Homeostasis Is a Factor in the Pathogenesis of Endometriosis.

    Science.gov (United States)

    Albertsen, Hans M; Ward, Kenneth

    2017-06-01

    Endometriosis, defined by the presence of ectopic endometrial lesions, is a common disease in reproductive-age women that profoundly affects patients' quality of life. Various pathogenic models have been proposed, but the origin of endometriosis remains elusive. In this article, we propose that the mesothelial barrier, which protects the underlying stroma from endometrial transplants present in retrograde menstrual fluid, can be compromised by activation of the epithelial to mesenchymal transition (EMT) repair mechanism that lead to temporary loss of barrier integrity. Absent of the mesothelial barrier, endometrial cells can more readily adhere to the underlying peritoneal stroma and establish endometrial lesions. The hypothesis is based on the clinical and experimental observations that correlate the location of endometrial lesions with areas of mesothelial damage, together with genetic evidence that 4 genes associated with endometriosis are direct regulators of the actin-cytoskeleton, which coordinates mesothelial barrier integrity. It supports past observations that implicate the peritoneum in the pathogenesis of endometriosis and unifies previously disparate theories that endometriosis may be triggered by infection, mechanical damage, and inflammation since each of these mechanisms can induce EMT in the mesothelium. If the hypothesis is correct, inhibition of EMT in the mesothelial barrier provides a novel paradigm for the prevention and treatment of endometriosis.

  13. Regulation of Cross-holdings between European Companies

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2003-01-01

    Cross-holdings can be a barrier to takeovers, and they may have other disadvantages. This article analyses how cross-holdings may be regulated to avoid these negative effects.......Cross-holdings can be a barrier to takeovers, and they may have other disadvantages. This article analyses how cross-holdings may be regulated to avoid these negative effects....

  14. The incremental role of trait emotional intelligence on perceived cervical screening barriers.

    Science.gov (United States)

    Costa, Sebastiano; Barberis, Nadia; Larcan, Rosalba; Cuzzocrea, Francesca

    2018-02-13

    Researchers have become increasingly interested in investigating the role of the psychological aspects related to the perception of cervical screening barriers. This study investigates the influence of trait EI on perceived cervical screening barriers. Furthermore, this study investigates the incremental validity of trait EI beyond the Big Five, as well as emotion regulation in the perceived barrier towards the Pap test as revealed in a sample of 206 Italian women that were undergoing cervical screening. Results have shown that trait EI is negatively related to cervical screening barriers. Furthermore, trait EI can be considered as a strong incremental predictor of a woman's perception of screening over and above the Big Five, emotion regulation, age, sexual intercourse experience and past Pap test. Detailed information on the study findings and future research directions are discussed.

  15. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors.

    Science.gov (United States)

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E; O'Carroll, Simon J; Graham, E Scott

    2016-01-27

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors.

  16. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress.

    Science.gov (United States)

    Arredondo Zamarripa, David; Díaz-Lezama, Nundehui; Meléndez García, Rodrigo; Chávez Balderas, Jesús; Adán, Norma; Ledesma-Colunga, Maria G; Arnold, Edith; Clapp, Carmen; Thebault, Stéphanie

    2014-01-01

    Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK) production contributes to the increased transport through the blood-retina barrier (BRB) in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE) components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO) synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC), blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC) monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19) cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS) in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies.

  17. Vasoinhibins regulate the inner and outer blood-retinal barrier and limit retinal oxidative stress

    Directory of Open Access Journals (Sweden)

    David eArredondo Zamarripa

    2014-10-01

    Full Text Available Vasoinhibins are prolactin fragments present in the retina, where they have been shown to prevent the hypervasopermeability associated with diabetes. Enhanced bradykinin (BK production contributes to the increased transport through the blood-retina barrier (BRB in diabetes. Here, we studied if vasoinhibins regulate BRB permeability by targeting the vascular endothelium and retinal pigment epithelium (RPE components of this barrier. Intravitreal injection of BK in male rats increased BRB permeability. Vasoinhibins prevented this effect, as did the B2 receptor antagonist Hoe-140. BK induced a transient decrease in mouse retinal and brain capillary endothelial monolayer resistance that was blocked by vasoinhibins. Both vasoinhibins and the nitric oxide (NO synthase inhibitor L-NAME, but not the antioxidant N-acetyl cysteine (NAC, blocked the transient decrease in bovine umbilical vein endothelial cell (BUVEC monolayer resistance induced by BK; this block was reversed by the NO donor DETANONOate. Vasoinhibins also prevented the BK-induced actin cytoskeleton redistribution, as did L-NAME. BK transiently decreased human RPE (ARPE-19 cell monolayer resistance, and this effect was blocked by vasoinhibins, L-NAME, and NAC. DETANONOate reverted the blocking effect of vasoinhibins. Similar to BK, the radical initiator Luperox induced a reduction in ARPE-19 cell monolayer resistance, which was prevented by vasoinhibins. These effects on RPE resistance coincided with actin cytoskeleton redistribution. Intravitreal injection of vasoinhibins reduced the levels of reactive oxygen species (ROS in retinas of streptozotocin-induced diabetic rats, particularly in the RPE and capillary-containing layers. Thus, vasoinhibins reduce BRB permeability by targeting both its main inner and outer components through NO- and ROS-dependent pathways, offering potential treatment strategies against diabetic retinopathies.

  18. Barriers to Business Model Innovation in Swedish Agriculture

    Directory of Open Access Journals (Sweden)

    Olof Sivertsson

    2015-02-01

    Full Text Available Swedish agricultural companies, especially small farms, are struggling to be profitable in difficult economic times. It is a challenge for Swedish farmers to compete with imported products on prices. The agricultural industry, however, supports the view that through business model innovation, farms can increase their competitive advantage. This paper identifies and describes some of the barriers Swedish small farms encounter when they consider business model innovation. A qualitative approach is used in the study. Agriculture business consultants were interviewed. In a focus group led by the researchers, farmers discussed business model innovation, including the exogenous and endogenous barriers to such innovation. The paper concludes many barriers exist when farmers consider innovation of agricultural business models. Some barriers are caused by human factors, such as individuals’ attitudes, histories, and traditions. Other barriers are more contextual in nature and relate to a particular industry or company setting. Still other barriers, such as government regulations, value chain position, and weather, are more abstract. All barriers, however, merit attention when Swedish agricultural companies develop new business models.

  19. Saccharomyces boulardii CNCM I-745 Restores intestinal Barrier Integrity by Regulation of E-cadherin Recycling.

    Science.gov (United States)

    Terciolo, Chloé; Dobric, Aurélie; Ouaissi, Mehdi; Siret, Carole; Breuzard, Gilles; Silvy, Françoise; Marchiori, Bastien; Germain, Sébastien; Bonier, Renaté; Hama, Adel; Owens, Roisin; Lombardo, Dominique; Rigot, Véronique; André, Frédéric

    2017-08-01

    Alteration in intestinal permeability is the main factor underlying the pathogenesis of many diseases affecting the gut, such as inflammatory bowel disease [IBD]. Characterization of molecules targeting the restoration of intestinal barrier integrity is therefore vital for the development of alternative therapies. The yeast Saccharomyces boulardii CNCM I-745 [Sb], used to prevent and treat antibiotic-associated infectious and functional diarrhea, may have a beneficial effect in the treatment of IBD. We analyzed the impact of Sb supernatant on tissue integrity and components of adherens junctions using cultured explants of colon from both IBD and healthy patients. To evaluate the pathways by which Sb regulates the expression of E-cadherin at the cell surface, we developed in vitro assays using human colonic cell lines, including cell aggregation, a calcium switch assay, real-time measurement of transepithelial electrical resistance [TEER] and pulse-chase experiments. We showed that Sb supernatant treatment of colonic explants protects the epithelial morphology and maintains E-cadherin expression at the cell surface. In vitro experiments revealed that Sb supernatant enhances E-cadherin delivery to the cell surface by re-routing endocytosed E-cadherin back to the plasma membrane. This process, involving Rab11A-dependent recycling endosome, leads to restoration of enterocyte adherens junctions, in addition to the overall restoration and strengthening of intestinal barrier function. These findings open new possibilities of discovering novel options for prevention and therapy of diseases that affect intestinal permeability. Copyright © 2017 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

  20. Association between genetic polymorphisms in the human interleukin-7 receptor alpha-chain and inhalation allergy

    DEFF Research Database (Denmark)

    Shamim, Z; Müller, K; Svejgaard, A

    2007-01-01

    Thymic stromal-derived lymphopoietin (TSLP) and interleukin-7 share a common receptor chain, IL-7Ralpha. IL-7 is involved in T-cell homeostasis, and TSLP induces production of pro-allergic cytokines. The gene encoding the IL-7Ralpha chain is polymorphic, and investigation of inhalation allergic p...

  1. IL-33 and Thymic Stromal Lymphopoietin in mast cell functions

    NARCIS (Netherlands)

    Saluja, Rohit; Zoltowska, Anna; Ketelaar, Maria Elizabeth; Nilsson, Gunnar

    2016-01-01

    Thymic Stromal Lymphopoietin (TSLP) and Interleukin 33 (IL-33) are two cytokines released by cells that are in proximity to our environment, e.g., keratinocytes of the skin and epithelial cells of the airways. Pathogens, allergens, chemicals and other agents induce the release of TSLP and IL-33,

  2. Overcoming natural replication barriers: differential helicase requirements.

    Science.gov (United States)

    Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

    2012-02-01

    DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

  3. Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like mice model

    Directory of Open Access Journals (Sweden)

    Li CX

    2016-02-01

    Full Text Available Chun-xiao Li,* Hua-guo Li,* Hui Zhang,* Ru-hong Cheng, Ming Li, Jian-ying Liang, Yan Gu, Bo Ling, Zhi-rong Yao, Hong Yu Department of Dermatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Atopic dermatitis (AD is one of the most common inflammatory cutaneous diseases. Thymic stromal lymphopoietin (TSLP has been demonstrated to be an important immunologic factor in the pathogenesis of AD. The production of TSLP can be induced by a high level of intracellular calcium concentration and activation of the receptor-interacting protein 2/caspase-1/NF-κB pathway. Andrographolide (ANDRO, a natural bicyclic diterpenoid lactone, has been found to exert anti-inflammatory effects in gastrointestinal inflammatory disorders through suppressing the NF-κB pathway. Objective: To explore the effect of ANDRO on the production of TSLP in human mast cells and AD mice model. Methods: We utilized enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, and immunofluorescence staining assay to investigate the effects of ANDRO on AD. Results: ANDRO ameliorated the increase in the intracellular calcium, protein, and messenger RNA levels of TSLP induced by phorbol myristate acetate/calcium ionophore A23187, through the blocking of the receptor-interacting protein 2/caspase-1/NF-κB pathway in human mast cell line 1 cells. ANDRO, via oral or local administration, also attenuated clinical symptoms in 2,4-dinitrofluorobenzene-induced AD mice model and suppressed the levels of TSLP in lesional skin. Conclusion: Taken together, ANDRO may be a potential therapeutic agent for AD through suppressing the expression of TSLP. Keywords: atopic dermatitis, thymic stromal lymphopoietin, andrographolide, human mast cell

  4. Levels of physical activity, motivation and barriers to participation in university students.

    Science.gov (United States)

    Sevil, Javier; Práxedes, Alba; Abarca-Sos, Alberto; Del Villar, Fernando; García-González, Luis

    2016-10-01

    Grounded in self-determination theory and trans-theoretical model applied to exercise, the aim of this study was to analyse the existing relationships between physical activity (PA) carried out by university students, perceived barriers to PA, motivation to PA and stages of change. 901 Spanish students took part in the study (408 men, 493 women; mean age 22.59±3.59), who completed the Behavioural Regulation in Exercise Questionnaire (BREQ-3), Scale of Barriers to PA, Stages of Change and the International Physical Activity Questionnaire - Short Form (IPAQ-SF). Noteworthy among the findings is the positive relationship between the more autonomous regulation forms, especially integrated regulation, and the moderate to vigorous PA (MVPA) levels. However, barriers to participatrion are negatively related to PA levels and the more self-determined forms of motivation. Finally, students in action and maintenance stages, and those who comply with the recommendations on PA present higher values in the more self-determined motivation forms and lower values in barriers to participation in PA. The study shows the importance of addressing the analysis of variables associated with engagement in PA in the university population to develop healthy policies and intervention programmes that can establish a series of healthy and more active habits in the youth-adult stage. The appropriateness of promoting more self-determined motivation forms is highlighted, especially integrated regulation, to have an impact on higher levels of MVPA.

  5. Implementation status and barriers of good manufacturing practice ...

    African Journals Online (AJOL)

    Removal of implementation barriers could be considered, including strengthening personnel competence, improving the quality management system and enhancing the international communication with advanced GMP regulators. Keywords: good manufacturing practice, GMP, Chinese patent medicine, traditional Chinese ...

  6. Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation

    Science.gov (United States)

    Fasano, Alessio

    2008-01-01

    The anatomical and functional arrangement of the gastrointestinal tract suggests that this organ, beside its digestive and absorptive functions, regulates the trafficking of macromolecules between the environment and the host through a barrier mechanism. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions, structures whose physiological modulation is mediated by, among others, the recently described protein zonulin. To prevent harm and minimize inflammation, the same paracellular pathway, in concert with the gut-associated lymphoid tissue and the neuroendocrine network, controls the equilibrium between tolerance and immunity to nonself antigens. The zonulin pathway has been exploited to deliver drugs, macromolecules, or vaccines that normally would not be absorbed through the gastrointestinal mucosal barrier. However, if the tightly regulated trafficking of macromolecules is jeopardized secondary to prolonged zonulin up-regulation, the excessive flow of nonself antigens in the intestinal submucosa can cause both intestinal and extraintestinal autoimmune disorders in genetically susceptible individuals. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier competency. Understanding the role of zonulin-dependent intestinal barrier dysfunction in the pathogenesis of autoimmune diseases is an area of translational research that encompasses many fields. PMID:18832585

  7. Floating convection barrier for evaporation source

    International Nuclear Information System (INIS)

    1975-01-01

    A floating matrix of titanium in an uranium evaporation source, melted by an electron beam, serves as a barrier for preventing cooler material from reaching the evaporation area. This construction allows a big volume of melted uranium to be present and new uranium to be furnished in regulated intervals without manual intervention

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

    Science.gov (United States)

    Ling, Xiang; Linglong, Peng; 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 zonulin release (P zonulin (P zonulin protein release and improvement of intestinal TJ integrity.

  9. Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

    International Nuclear Information System (INIS)

    Monnot, Andrew D.; Behl, Mamta; Ho, Sanna; Zheng, Wei

    2011-01-01

    Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (− 56%) in CSF Cu levels (p < 0.05), respectively; however, neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (− 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.

  10. Regulation of brain copper homeostasis by the brain barrier systems: Effects of Fe-overload and Fe-deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Monnot, Andrew D.; Behl, Mamta; Ho, Sanna; Zheng, Wei, E-mail: wzheng@purdue.edu

    2011-11-15

    Maintaining brain Cu homeostasis is vital for normal brain function. The role of systemic Fe deficiency (FeD) or overload (FeO) due to metabolic diseases or environmental insults in Cu homeostasis in the cerebrospinal fluid (CSF) and brain tissues remains unknown. This study was designed to investigate how blood-brain barrier (BBB) and blood-SCF barrier (BCB) regulated Cu transport and how FeO or FeD altered brain Cu homeostasis. Rats received an Fe-enriched or Fe-depleted diet for 4 weeks. FeD and FeO treatment resulted in a significant increase (+ 55%) and decrease (- 56%) in CSF Cu levels (p < 0.05), respectively; however, neither treatment had any effect on CSF Fe levels. The FeD, but not FeO, led to significant increases in Cu levels in brain parenchyma and the choroid plexus. In situ brain perfusion studies demonstrated that the rate of Cu transport into the brain parenchyma was significantly faster in FeD rats (+ 92%) and significantly slower (- 53%) in FeO rats than in controls. In vitro two chamber Transwell transepithelial transport studies using primary choroidal epithelial cells revealed a predominant efflux of Cu from the CSF to blood compartment by the BCB. Further ventriculo-cisternal perfusion studies showed that Cu clearance by the choroid plexus in FeD animals was significantly greater than control (p < 0.05). Taken together, our results demonstrate that both the BBB and BCB contribute to maintain a stable Cu homeostasis in the brain and CSF. Cu appears to enter the brain primarily via the BBB and is subsequently removed from the CSF by the BCB. FeD has a more profound effect on brain Cu levels than FeO. FeD increases Cu transport at the brain barriers and prompts Cu overload in the CNS. The BCB plays a key role in removing the excess Cu from the CSF.

  11. Investment opportunities and barriers. The effects of government policy

    International Nuclear Information System (INIS)

    Terzic, B.

    2002-01-01

    The following concepts regarding energy investment opportunities and barriers are explained in depth: Regulation; Profit; Value; Revenue constraints; Expense and cost constrains; Recommending use of UK's more recent regulatory model. (R.P.)

  12. Using self-regulation theory to examine patient goals, barriers, and facilitators for taking medication.

    Science.gov (United States)

    Kucukarslan, Suzan N; Thomas, Sheena; Bazzi, Abraham; Virant-Young, Deborah

    2009-12-01

    : Self-regulation theory predicts that patient behavior is determined by the patient's assessment of his/her condition (illness presentation) and related health goals. Patients will adapt their behavior to achieve those goals. However, there are multiple levels of goals. In such cases, those lower-level goals (health goals) that are strongly correlated with higher-level goals (i.e. quality of life [QOL]) are more likely to drive patient behavior. Medication non-compliance is a health behavior that challenges healthcare practitioners. Thus, the primary aim of this paper is to explore the relationship between the lower-level goals for taking medication with higher-level goals. This paper also identifies patient-perceived barriers and facilitators toward achieving goals as they may relate to patients' illness representation. : To identify lower- and higher-level goals associated with medication use for chronic conditions. To determine if there is a relationship between higher-level (global) goals and lower-level (health-related) goals. To identify patient-perceived facilitators and barriers to achieving those goals. : This was a prospective, observational study using a mailed survey. The setting was a US Midwestern state-wide survey. Participants were patients living in the community with hypertension, heart disease, diabetes mellitus, or arthritis, and taking prescription medication for any one of those conditions. The main outcome measures were lower- and higher-level goals related to medication use. The survey asked the participants if they had achieved their goals and to identify factors that may pose as barriers or facilitators to achieving them. Pearson correlation was used to test the relationship between the lower- and higher-level goals at p goals existed (p = 0.03). Preventing future health problems was the most important lower-level goal for almost half of the respondents. Approximately 43% of the respondents said 'improving or maintaining quality of

  13. Cell- and virus-mediated regulation of the barrier-to-autointegration factor's phosphorylation state controls its DNA binding, dimerization, subcellular localization, and antipoxviral activity.

    Science.gov (United States)

    Jamin, Augusta; Wicklund, April; Wiebe, Matthew S

    2014-05-01

    Barrier-to-autointegration factor (BAF) is a DNA binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. This antiviral function involves BAF's ability to condense double-stranded DNA and subsequently prevent viral DNA replication. In recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus B1 kinase and cellular enzymes is likely a key regulator of multiple BAF functions; however, the precise mechanisms are poorly understood. Here we analyzed how phosphorylation impacts BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity through the characterization of BAF phosphomimetic and unphosphorylatable mutants. Our studies demonstrate that increased phosphorylation enhances BAF's mobilization from the nucleus to the cytosol, while dephosphorylation restricts BAF to the nucleus. Phosphorylation also impairs both BAF's dimerization and its DNA binding activity. Furthermore, our studies of BAF's antiviral activity revealed that hyperphosphorylated BAF is unable to suppress viral DNA replication or virus production. Interestingly, the unphosphorylatable BAF mutant, which is capable of binding DNA but localizes predominantly to the nucleus, was also incapable of suppressing viral replication. Thus, both DNA binding and localization are important determinants of BAF's antiviral function. Finally, our examination of how phosphatases are involved in regulating BAF revealed that PP2A dephosphorylates BAF during vaccinia infection, thus counterbalancing the activity of the B1 kinase. Altogether, these data demonstrate that phosphoregulation of BAF by viral and cellular enzymes modulates this protein at multiple molecular levels, thus determining its effectiveness as an antiviral factor and likely other functions as well. The barrier-to-autointegration factor (BAF) contributes to cellular genomic integrity in multiple ways

  14. Market and policy barriers to energy storage deployment :

    Energy Technology Data Exchange (ETDEWEB)

    Bhatnagar, Dhruv; Currier, Aileen B.; Hernandez, Jacquelynne; Ma, Ookie; Kirby, Brendan

    2013-09-01

    Electric energy storage technologies have recently been in the spotlight, discussed as essential grid assets that can provide services to increase the reliability and resiliency of the grid, including furthering the integration of variable renewable energy resources. Though they can provide numerous grid services, there are a number of factors that restrict their current deployment. The most significant barrier to deployment is high capital costs, though several recent deployments indicate that capital costs are decreasing and energy storage may be the preferred economic alternative in certain situations. However, a number of other market and regulatory barriers persist, limiting further deployment. These barriers can be categorized into regulatory barriers, market (economic) barriers, utility and developer business model barriers, crosscutting barriers and technology barriers. This report, through interviews with stakeholders and review of regulatory filings in four regions roughly representative of the United States, identifies the key barriers restricting further energy storage development in the country. The report also includes a discussion of possible solutions to address these barriers and a review of initiatives around the country at the federal, regional and state levels that are addressing some of these issues. Energy storage could have a key role to play in the future grid, but market and regulatory issues have to be addressed to allow storage resources open market access and compensation for the services they are capable of providing. Progress has been made in this effort, but much remains to be done and will require continued engagement from regulators, policy makers, market operators, utilities, developers and manufacturers.

  15. The role of multiple barriers in assuring waste package reliability

    International Nuclear Information System (INIS)

    Bradford, R.M.

    1993-08-01

    Yucca Mountain in southwestern Nevada is being studied as a potential repository site for the permanent storage of high-level nuclear waste. Regulators have set performance standards that the potential repository must meet in order to obtain regulatory approval. Nuclear Regulatory Commission (NRC) regulations state that containment of radioactivity must be ''substantially complete'' for the first 1000 years after closure of the facility. Thereafter, the acceptable annual limit on releases is 1/100,000 of each radionuclide remaining in the inventory after 1000 years. To demonstrate that the potential facility is in compliance with the regulations, it is necessary to obtain some understanding of the probability distribution of the cumulative quantity of releases by certain time points. This paper will discuss the probability distribution of waste container lifetimes and how the understanding of this distribution will play a role in finding the distribution of the release quantities over time. It will be shown that, for reasonable assumptions about the process of barrier failure, the reliability of a multiple-barrier container can be achieved and demonstrated much more readily than a container consisting of a single barrier. The discussion will focus primarily on the requirement of substantially complete containment for the first 1000 years

  16. Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

    Science.gov (United States)

    Chen, Chuanli; Wang, Pei; Su, Qin; Wang, Shiliang; Wang, Fengjun

    2012-01-01

    Background Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. Conclusions/Significance The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. PMID:22529961

  17. Regulatory barriers blocking standardization of interoperability.

    Science.gov (United States)

    Zhong, Daidi; Kirwan, Michael J; Duan, Xiaolian

    2013-07-12

    Developing and implementing a set of personal health device interoperability standards is key to cultivating a healthy global industry ecosystem. The standardization organizations, including the Institute of Electrical and Electronics Engineers 11073 Personal Health Device Workgroup (IEEE 11073-PHD WG) and Continua Health Alliance, are striving for this purpose. However, factors like the medial device regulation, health policy, and market reality have placed non-technical barriers over the adoption of technical standards throughout the industry. These barriers have significantly impaired the motivations of consumer device vendors who desire to enter the personal health market and the overall success of personal health industry ecosystem. In this paper, we present the affect that these barriers have placed on the health ecosystem. This requires immediate action from policy makers and other stakeholders. The current regulatory policy needs to be updated to reflect the reality and demand of consumer health industry. Our hope is that this paper will draw wide consensus amongst its readers, policy makers, and other stakeholders.

  18. Occupational health regulations and health workers: protection or vulnerability?

    OpenAIRE

    Lethbridge, Jane

    2008-01-01

    Several trade agreements include occupational health and safety regulations but there are many barriers to implementation. Mechanisms for sanctions are often weak but the lack of political will is the biggest barrier.

  19. Barriers to guideline-compliant psoriasis care: analyses and concepts.

    Science.gov (United States)

    Eissing, L; Radtke, M A; Zander, N; Augustin, M

    2016-04-01

    Despite the availability of effective therapeutics and evidence-based treatment guidelines, a substantial proportion of patients with moderate-to-severe psoriasis does not receive appropriate care. This under-provision of health care may cause further worsening of health, remarkable limitations of the patient's quality of life, and indirect costs for the health care system. In order to provide guideline-compliant care for every psoriasis patient, it is important to identify barriers obstructing optimal care. Studies have identified various barriers on the physician's and on the patient's side; however, respective studies approached only single barriers, and not all of them in the context of psoriasis. Other publications that describe barriers systematically did not focus on psoriasis either. The objective of this literature review was to identify barriers and facilitators, based on studies analysing quality of care and single barriers, resulting in a comprehensive model of causal factors. Our analyses revealed three categories of barriers - patient-related, physician-related and external factors: On the patient side, we found non-adherence to therapies to be an important barrier, often in close association with psychiatric factors. Barriers on the physician's side predominantly are incomplete knowledge of the guidelines as well as the complexity of psoriasis comorbidity. In some countries, payment for patients with complex disease status is poor and inconsistent reimbursement regulations potentially interfere with optimal care. The current analysis indicates that most barriers are interdependent. Thus, measures approaching related barriers simultaneously are required. To improve care for psoriasis patients, further studies systematically addressing all potentially relevant barriers in conjoint are needed. © 2015 European Academy of Dermatology and Venereology.

  20. Regulatory issues and assumptions associated with polymers for subsurface barriers surrounding buried waste

    International Nuclear Information System (INIS)

    Heiser, J.; Siskind, B.

    1993-01-01

    One of the options for control of contaminant migration from buried waste sites is the construction of a subsurface barrier that consists of a wall of low permeability material. Subsurface barriers will improve remediation performance by removing pathways for contaminant transport due to groundwater movement, meteorological water infiltration, vapor- and gas-phase transport, transpiration, etc. Subsurface barriers may be used to open-quotes directclose quotes contaminant movement to collection sumps/lysimeters in cases of unexpected remediation failures or transport mechanisms, to contain leakage from underground storage tanks, and to restrict in-situ soil cleanup operation and chemicals. Brookhaven National Laboratory is currently investigating advanced polymer materials for subsurface barriers. This report addresses the regulatory aspects of using of non-traditional polymer materials as well as soil-bentonite or cement-bentonite mixtures for such barriers. The regulatory issues fall into two categories. The first category consists of issues associated with the acceptability of subsurface barriers to the Environmental Protection Agency (EPA) as a method for achieving waste site performance improvement. The second category encompasses those regulatory issues concerning health, safety and the environment which must be addressed regarding barrier installation and performance, especially if non-traditional materials are to be used. Since many of EPA's concerns regarding subsurface barriers focus on the chemicals used during installation of these barriers the authors discuss the results of a search of the Federal Register and the Code of Federal Regulations for references in Titles 29 and 40 pertaining to key chemicals likely to be utilized in installing non-traditional barrier materials. The use of polymeric materials in the construction industry has been accomplished with full compliance with the applicable health, safety, and environmental regulations

  1. Myosin light chain kinase mediates intestinal barrier disruption following burn injury.

    Directory of Open Access Journals (Sweden)

    Chuanli Chen

    Full Text Available BACKGROUND: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC phosphorylation mediated by MLC kinase (MLCK is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. METHODOLOGY/PRINCIPAL FINDINGS: Male balb/c mice were assigned randomly to either sham burn (control or 30% total body surface area (TBSA full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg, an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. CONCLUSIONS/SIGNIFICANCE: The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury.

  2. Endothelial Regulator of Calcineurin 1 Promotes Barrier Integrity and Modulates Histamine-Induced Barrier Dysfunction in Anaphylaxis

    DEFF Research Database (Denmark)

    Ballesteros-Martinez, Constanza; Mendez-Barbero, Nerea; Montalvo-Yuste, Alma

    2017-01-01

    Anaphylaxis, the most serious and life-threatening allergic reaction, produces the release of inflammatory mediators by mast cells and basophils. Regulator of calcineurin 1 (Rcan1) is a negative regulator of mast-cell degranulation. The action of mediators leads to vasodilation and an increase in...

  3. Overcoming regulatory barriers: DOE environmental technology development program

    International Nuclear Information System (INIS)

    Kurtyka, B.M.; Clodfelter-Schumack, K.; Evans, T.T.

    1995-01-01

    The potential to improve environmental conditions via compliance or restoration is directly related to the ability to produce and apply innovative technological solutions. However, numerous organizations, including the US General Accounting Office (GAO), the EPA National Advisory Council for Environmental Policy and Technology (NACEPT), the DOE Environmental Management Advisory Board (EMAB), and the National Science and Technology Council (NSTC) have determined that significant regulatory barriers exist that inhibit the development and application of these technologies. They have noted the need for improved efforts in identifying and rectifying these barriers for the purpose of improving the technology development process, providing innovative alternatives, and enhancing the likelihood of technology acceptance by all. These barriers include, among others, regulator and user bias against ''unknown/unproven'' technologies; multi-level/multi-media permit disincentives; potential liability of developers and users for failed implementation; wrongly defined or inadequate data quality objectives: and lack of customer understanding and input. The ultimate goal of technology development is the utilization of technologies. This paper will present information on a number of regulatory barriers hindering DOE's environmental technology development program and describe DOE efforts to address these barriers

  4. Studying Executive Barriers on Rationalizing the Size of Iranian Government

    Directory of Open Access Journals (Sweden)

    Mohammad Hussein Rahmati

    2012-01-01

    Full Text Available To rationalize the size of government, Act on adjusting a part of government‟s financial rules is approved and the government is obliged to assign a part of its activities through (1 services by nonpublic sector, (2 partnership with nonpublic sector, and (3 assigning the management to nonpublic sector. There are many barriers in executing this law. The present study derived from a field study tries to provide a report on the performance of various organs in Qom province on executing this law and identifies the executive barriers and provides practical proposals to remove them.Overall, seventeen organs in Qom are subjected to this law of which five organs are selected as our sample. In this respect, different documents were studied, ten interviews were conducted and one hundred and four executive barriers and forty seven operational proposals including twenty three barriers and eleven proposals in organization and structure area, sixteen barriers and five proposals in administrative technology and working processes area, thirty two barriers and twelve proposals in human resources area, twenty one barriers and eight proposals in laws and regulations area and twelve barriers and eleven proposals in management area have been analyzed and summarized regarding their contents.

  5. Trypanosome infection establishment in the tsetse fly gut is influenced by microbiome-regulated host immune barriers.

    Directory of Open Access Journals (Sweden)

    Brian L Weiss

    Full Text Available Tsetse flies (Glossina spp. vector pathogenic African trypanosomes, which cause sleeping sickness in humans and nagana in domesticated animals. Additionally, tsetse harbors 3 maternally transmitted endosymbiotic bacteria that modulate their host's physiology. Tsetse is highly resistant to infection with trypanosomes, and this phenotype depends on multiple physiological factors at the time of challenge. These factors include host age, density of maternally-derived trypanolytic effector molecules present in the gut, and symbiont status during development. In this study, we investigated the molecular mechanisms that result in tsetse's resistance to trypanosomes. We found that following parasite challenge, young susceptible tsetse present a highly attenuated immune response. In contrast, mature refractory flies express higher levels of genes associated with humoral (attacin and pgrp-lb and epithelial (inducible nitric oxide synthase and dual oxidase immunity. Additionally, we discovered that tsetse must harbor its endogenous microbiome during intrauterine larval development in order to present a parasite refractory phenotype during adulthood. Interestingly, mature aposymbiotic flies (Gmm(Apo present a strong immune response earlier in the infection process than do WT flies that harbor symbiotic bacteria throughout their entire lifecycle. However, this early response fails to confer significant resistance to trypanosomes. Gmm(Apo adults present a structurally compromised peritrophic matrix (PM, which lines the fly midgut and serves as a physical barrier that separates luminal contents from immune responsive epithelial cells. We propose that the early immune response we observe in Gmm(Apo flies following parasite challenge results from the premature exposure of gut epithelia to parasite-derived immunogens in the absence of a robust PM. Thus, tsetse's PM appears to regulate the timing of host immune induction following parasite challenge. Our results

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

    Directory of Open Access Journals (Sweden)

    Xiang Ling

    Full Text Available 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

  7. β-Glucan Size Controls Dectin-1-Mediated Immune Responses in Human Dendritic Cells by Regulating IL-1β Production

    Directory of Open Access Journals (Sweden)

    Matthew J. Elder

    2017-07-01

    Full Text Available Dectin-1/CLEC7A is a pattern recognition receptor that recognizes β-1,3 glucans, and its stimulation initiates signaling events characterized by the production of inflammatory cytokines from human dendritic cells (DCs required for antifungal immunity. β-glucans differ greatly in size, structure, and ability to activate effector immune responses from DC; as such, small particulate β-glucans are thought to be poor activators of innate immunity. We show that β-glucan particle size is a critical factor contributing to the secretion of cytokines from human DC; large β-glucan-stimulated DC generate significantly more IL-1β, IL-6, and IL-23 compared to those stimulated with the smaller β-glucans. In marked contrast, the secretion of TSLP and CCL22 were found to be insensitive to β-glucan particle size. Furthermore, we show that the capacity to induce phagocytosis, and the relative IL-1β production determined by β-glucan size, regulates the composition of the cytokine milieu generated from DC. This suggests that β-glucan particle size is critically important in orchestrating the nature of the immune response to fungi.

  8. Strategies to improve drug delivery across the blood-brain barrier.

    Science.gov (United States)

    de Boer, Albertus G; Gaillard, Pieter J

    2007-01-01

    The blood-brain barrier (BBB), together with the blood-cerebrospinal-fluid barrier, protects and regulates the homeostasis of the brain. However, these barriers also limit the transport of small-molecule and, particularly, biopharmaceutical drugs such as proteins, genes and interference RNA to the brain, thereby limiting the treatment of many brain diseases. As a result, various drug delivery and targeting strategies are currently being developed to enhance the transport and distribution of drugs into the brain. In this review, we discuss briefly the biology and physiology of the BBB as the most important barrier for drug transport to the brain and, in more detail, the possibilities for delivering large-molecule drugs, particularly genes, by receptor-mediated nonviral drug delivery to the (human) brain. In addition, the systemic and intracellular pharmacokinetics of nonviral gene delivery, together with targeted brain imaging, are reviewed briefly.

  9. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  10. Blood-brain barrier transport of drugs for the treatment of brain diseases.

    Science.gov (United States)

    Gabathuler, Reinhard

    2009-06-01

    The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

  11. Regulatory Barriers Blocking Standardization of Interoperability

    OpenAIRE

    Zhong, Daidi; Kirwan, Michael J; Duan, Xiaolian

    2013-01-01

    Developing and implementing a set of personal health device interoperability standards is key to cultivating a healthy global industry ecosystem. The standardization organizations, including the Institute of Electrical and Electronics Engineers 11073 Personal Health Device Workgroup (IEEE 11073-PHD WG) and Continua Health Alliance, are striving for this purpose. However, factors like the medial device regulation, health policy, and market reality have placed non-technical barriers over the ad...

  12. The Status of Industrial Ecology in Australia: Barriers and Enablers

    Directory of Open Access Journals (Sweden)

    Glen D. Corder

    2014-03-01

    Full Text Available Drawing on current international industrial ecology thinking and experiences with Australian initiatives, this article critically overviews the current status of industrial ecology in Australia and examines the barriers and potential strategies to realise greater uptake and application of the concept. The analysis is conducted across three categories: heavy industrial areas (including Kwinana and Gladstone, mixed industrial parks (Wagga Wagga and Port Melbourne, and waste exchange networks, and identifies the past and future significance of seven different types of barriers—regulation, information, community, economic, technical, cooperation and trust, commitment to sustainable development—for each of the three categories. The outcomes from this analysis highlight that regulation, information, and economic barriers for heavy industrial area and mixed industrial parks, and economic and technical barriers for waste exchange networks are the current and future focus for industrial ecology applications in Australia. These findings appear to be consistent with recently published frameworks and learnings. The authors propose key questions that could enhance greater adoption of industrial ecology applications in Australia and acknowledge that international research and experiences, while partly providing answers to these questions, need to be adapted and refined for the Australian context.

  13. Astrocyte–endothelial interactions and blood–brain barrier permeability*

    Science.gov (United States)

    Abbott, N Joan

    2002-01-01

    The blood–brain barrier (BBB) is formed by brain endothelial cells lining the cerebral microvasculature, and is an important mechanism for protecting the brain from fluctuations in plasma composition, and from circulating agents such as neurotransmitters and xenobiotics capable of disturbing neural function. The barrier also plays an important role in the homeostatic regulation of the brain microenvironment necessary for the stable and co-ordinated activity of neurones. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of more complex tight junctions than in other capillary endothelia, and a number of specific transport and enzyme systems which regulate molecular traffic across the endothelial cells. Transporters characteristic of the BBB phenotype include both uptake mechanisms (e.g. GLUT-1 glucose carrier, L1 amino acid transporter) and efflux transporters (e.g. P-glycoprotein). In addition to a role in long-term barrier induction and maintenance, astrocytes and other cells can release chemical factors that modulate endothelial permeability over a time-scale of seconds to minutes. Cell culture models, both primary and cell lines, have been used to investigate aspects of barrier induction and modulation. Conditioned medium taken from growing glial cells can reproduce some of the inductive effects, evidence for involvement of diffusible factors. However, for some features of endothelial differentiation and induction, the extracellular matrix plays an important role. Several candidate molecules have been identified, capable of mimicking aspects of glial-mediated barrier induction of brain endothelium; these include TGFβ, GDNF, bFGF, IL-6 and steroids. In addition, factors secreted by brain endothelial cells including leukaemia inhibitory factor (LIF) have been shown to induce astrocytic differentiation. Thus endothelium and astrocytes are involved in two-way induction. Short-term modulation of brain

  14. Sprache als Barriere (Language as a Barrier)

    Science.gov (United States)

    Mattheier, Klaus

    1974-01-01

    The concept of language barrier has its derivations in the fields of dialectology, sociology and psychology. In contemporary usage however, the concept has two meanings i.e. regional-cultural barrier and socio-cultural barrier. (Text is in German.) (DS)

  15. Transcription profiling suggests that mitochondrial topoisomerase IB acts as a topological barrier and regulator of mitochondrial DNA transcription.

    Science.gov (United States)

    Dalla Rosa, Ilaria; Zhang, Hongliang; Khiati, Salim; Wu, Xiaolin; Pommier, Yves

    2017-12-08

    Mitochondrial DNA (mtDNA) is essential for cell viability because it encodes subunits of the respiratory chain complexes. Mitochondrial topoisomerase IB (TOP1MT) facilitates mtDNA replication by removing DNA topological tensions produced during mtDNA transcription, but it appears to be dispensable. To test whether cells lacking TOP1MT have aberrant mtDNA transcription, we performed mitochondrial transcriptome profiling. To that end, we designed and implemented a customized tiling array, which enabled genome-wide, strand-specific, and simultaneous detection of all mitochondrial transcripts. Our technique revealed that Top1mt KO mouse cells process the mitochondrial transcripts normally but that protein-coding mitochondrial transcripts are elevated. Moreover, we found discrete long noncoding RNAs produced by H-strand transcription and encompassing the noncoding regulatory region of mtDNA in human and murine cells and tissues. Of note, these noncoding RNAs were strongly up-regulated in the absence of TOP1MT. In contrast, 7S DNA, produced by mtDNA replication, was reduced in the Top1mt KO cells. We propose that the long noncoding RNA species in the D-loop region are generated by the extension of H-strand transcripts beyond their canonical stop site and that TOP1MT acts as a topological barrier and regulator for mtDNA transcription and D-loop formation.

  16. Trends in drug delivery through tissue barriers containing tight junctions.

    Science.gov (United States)

    Tscheik, Christian; Blasig, Ingolf E; Winkler, Lars

    2013-04-01

    A limitation in the uptake of many drugs is the restricted permeation through tissue barriers. There are two general ways to cross barriers formed by cell layers: by transcytosis or by diffusion through the intercellular space. In the latter, tight junctions (TJs) play the decisive role in the regulation of the barrier permeability. Thus, transient modulation of TJs is a potent strategy to improve drug delivery. There have been extensive studies on surfactant-like absorption enhancers. One of the most effective enhancers found is sodium caprate. However, this modulates TJs in an unspecific fashion. A novel approach would be the specific modulation of TJ-associated marvel proteins and claudins, which are the main structural components of the TJs. Recent studies have identified synthetic peptidomimetics and RNA interference techniques to downregulate the expression of targeted TJ proteins. This review summarizes current progress and discusses the impact on TJs' barrier function.

  17. Vulnerability of multiple-barrier systems

    International Nuclear Information System (INIS)

    Lind, N.C.

    1996-01-01

    'Vulnerability' is defined as the ratio of the probability of failure of a damaged system to the probability of failure of the undamaged system. This definition applies to all engineered systems and can be specialized to particular system types. Some disastrous failures (e.g., Chernobyl) have shown that systems can be highly vulnerable. open-quotes Defense in depthclose quotes is a powerful design principle, reducing vulnerability when the consequences of failure can be catastrophic. In the nuclear industry, defense in depth is widely used in radiation protection, reactor control, and shutdown systems. A multiple-barrier system is a simple example of a system that has defense in depth. The idea is that the system is not vulnerable. It cannot fail if one barrier fails because there is another to take its place. This idea is untenable in waste management, but a quantified vulnerability of a system can help owners, designers, and regulators decide how much defense in depth is desirable or enough. Many multiple-barrier systems can be modeled as systems of components physically in a series, each individually able to prevent failure. Components typically have bimodal distributions of the service time to failure, as illustrated by an example of application to a hypothetical nuclear fuel waste repository

  18. Mechanisms of pertussis toxin-induced barrier dysfunction in bovine pulmonary artery endothelial cell monolayers.

    Science.gov (United States)

    Patterson, C E; Stasek, J E; Schaphorst, K L; Davis, H W; Garcia, J G

    1995-06-01

    We have previously characterized several G proteins in endothelial cells (EC) as substrates for the ADP-ribosyltransferase activity of both pertussis (PT) and cholera toxin and described the modulation of key EC physiological responses, including gap formation and barrier function, by these toxins. In this study, we investigated the mechanisms involved in PT-mediated regulation of bovine pulmonary artery endothelial cells barrier function. PT caused a dose-dependent increase in albumin transfer, dependent upon action of the holotoxin, since neither the heat-inactivated PT, the isolated oligomer, nor the protomer induced EC permeability. PT-induced gap formation and barrier dysfunction were additive to either thrombin- or thrombin receptor-activating peptide-induced permeability, suggesting that thrombin and PT utilize distinct mechanisms. PT did not result in Ca2+ mobilization or alter either basal or thrombin-induced myosin light chain phosphorylation. However, PT stimulated protein kinase C (PKC) activation, and both PKC downregulation and PKC inhibition attenuated PT-induced permeability, indicating that PKC activity is involved in PT-induced barrier dysfunction. Like thrombin-induced permeability, the PT effect was blocked by prior increases in adenosine 3',5'-cyclic monophosphate. Thus PT-catalyzed ADP-ribosylation of a G protein (possibly other than Gi) may regulate cytoskeletal protein interactions, leading to EC barrier dysfunction.

  19. Barrier mechanisms in the Drosophila blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Samantha Jane Hindle

    2014-12-01

    Full Text Available The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many blood-brain barrier mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the blood-brain barrier can govern whole animal physiologies. This includes novel functions of blood-brain barrier gap junctions in orchestrating synchronized neuroblast proliferation, and of blood-brain barrier secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate blood-brain barrier anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  20. Fire barrier penetration seals in nuclear power plants

    International Nuclear Information System (INIS)

    Bajwa, C.S.; West, K.S.

    1996-07-01

    NNPs are divided into separated fire areas by fire-rated structural barriers. Fire-rated penetration seals are installed to seal certain openings in these barriers, in order to provide reasonable assurance that a fire will be confined to the area where it started. The staff of the Fire Protection Engineering Section, Office of Nuclear Reactor Regulation, US NRC, conducted a comprehensive technical assessment of penetration seals to address reports of potential problems, to determine if there were any problems of safety significance, and to determine if NRC requirements, review guidance, and inspection procedures are adequate. It was concluded that the general condition of penetration seal programs in industry is satisfactory, and that the actions taken in 1988 and 1994 had increased industry awareness of potential problems and resulted in more thorough surveillances, maintenance, and corrective actions. These previous staff actions, together with continued licensee upkeep of existing penetration seal programs and continued NRC inspections, are adequate to maintain public health and safety. Several minor revisions to the NRC fire protection regulation and review guidance are recommended

  1. Containment analysis of the 9975 transportation package with multiple barriers

    International Nuclear Information System (INIS)

    Vinson, D.W.

    2000-01-01

    A containment analysis has been performed for the scenario of non-routine transfer of a damaged 9975 package containing plutonium metal from K-area monitored storage to F-area on the Savannah River Site. A multiple barrier system with each barrier having a defined leakage rate of less than 1times10 -3 cm 3 /sec of air at Standard Temperature and Pressure was analyzed to determine the number of barriers needed to transport the package under normal transportation conditions to meet transportation requirements for containment. The barrier system was analyzed parametrically to achieve a composite system that met the federal requirements for the maximum permissible release rate given in Title 10 of the Code of Federal Regulations, Part 71. The multiple barrier system acts to retard the release of radioactivity. That is, a build-up in the radioactivity release rate occurs with time. For example, a system with three barriers (e.g., sealed plastic barrier) with a total free volume of 4,500 cm 3 could be transported for a total time of up to approximately 10 days with a release rate within the permissible rate. Additional number of barriers, or volume of the barriers, or both, would extend to this period of time. For example, a system with seven barriers with a total free volume of 4,500 cm 3 could be transported for up to 100 days. Plastic bags are one type of barrier used in movement of radioactive materials and capable of achieving a leak rate of 1times10 -3 cm 3 /sec of air at STP. Low-density polyethylene bags can withstand high temperature (up to 180 degrees C); a barrier thickness of 10 mils should be suitable for the barrier system. Additional requirements for barriers are listed in Section 4.2 of this report. Container testing per ANSI N14.5 is required to demonstrate leak rates for the individual barriers of less than 1times10 -3 cm 3 /sec

  2. Regulation of respiration and the oxygen diffusion barrier in soybean protect symbiotic nitrogen fixation from chilling-induced inhibition and shoots from premature senescence.

    Science.gov (United States)

    van Heerden, Philippus D R; Kiddle, Guy; Pellny, Till K; Mokwala, Phatlane W; Jordaan, Anine; Strauss, Abram J; de Beer, Misha; Schlüter, Urte; Kunert, Karl J; Foyer, Christine H

    2008-09-01

    Symbiotic nitrogen fixation is sensitive to dark chilling (7 degrees C-15 degrees C)-induced inhibition in soybean (Glycine max). To characterize the mechanisms that cause the stress-induced loss of nodule function, we examined nodule structure, carbon-nitrogen interactions, and respiration in two soybean genotypes that differ in chilling sensitivity: PAN809 (PAN), which is chilling sensitive, and Highveld Top (HT), which is more chilling resistant. Nodule numbers were unaffected by dark chilling, as was the abundance of the nitrogenase and leghemoglobin proteins. However, dark chilling decreased nodule respiration rates, nitrogenase activities, and NifH and NifK mRNAs and increased nodule starch, sucrose, and glucose in both genotypes. Ureide and fructose contents decreased only in PAN nodules. While the chilling-induced decreases in nodule respiration persisted in PAN even after return to optimal temperatures, respiration started to recover in HT by the end of the chilling period. The area of the intercellular spaces in the nodule cortex and infected zone was greatly decreased in HT after three nights of chilling, an acclimatory response that was absent from PAN. These data show that HT nodules are able to regulate both respiration and the area of the intercellular spaces during chilling and in this way control the oxygen diffusion barrier, which is a key component of the nodule stress response. We conclude that chilling-induced loss of symbiotic nitrogen fixation in PAN is caused by the inhibition of respiration coupled to the failure to regulate the oxygen diffusion barrier effectively. The resultant limitations on nitrogen availability contribute to the greater chilling-induced inhibition of photosynthesis in PAN than in HT.

  3. Understanding barriers to commercial-scale carbon capture and sequestration in the United States: An empirical assessment

    International Nuclear Information System (INIS)

    Davies, Lincoln L.; Uchitel, Kirsten; Ruple, John

    2013-01-01

    Although a potentially useful climate change mitigation tool, carbon capture and sequestration (CCS) efforts in the United States remain mired in demonstration and development. Prior studies suggest numerous reasons for this stagnation. This article empirically assesses those claims. Using an anonymous opinion survey completed by 229 CCS experts, we identified four primary barriers to CCS commercialization: (1) cost and cost recovery, (2) lack of a price signal or financial incentive, (3) long-term liability risks, and (4) lack of a comprehensive regulatory regime. These results give empirical weight to previous studies suggesting that CCS cost (and cost recovery) and liability risks are primary barriers to the technology. However, the need for comprehensive rather than piecemeal CCS regulation represents an emerging concern not previously singled out in the literature. Our results clearly show that the CCS community sees fragmented regulation as one of the most significant barriers to CCS deployment. Specifically, industry is united in its preference for a federal regulatory floor that is subject to state-level administration and sensitive to local conditions. Likewise, CCS experts share broad confidence in the technology's readiness, despite continued calls for commercial-scale demonstration projects before CCS is widely deployed. - Highlights: • We developed and distributed a unique CCS opinion survey. • Our analysis confirmed cost and liability as primary barriers to CCS deployment. • We identified regulatory barriers to CCS not previously singled out in the literature. • We address the need for comprehensive rather than piecemeal CCS regulation

  4. Perception of barriers for expansion of electricity grids in the European Union

    International Nuclear Information System (INIS)

    Battaglini, Antonella; Komendantova, Nadejda; Brtnik, Patricia; Patt, Anthony

    2012-01-01

    Many of the scenarios for decarbonising the European energy system involve the integration of large-scale and decentralised renewable energy sources, such as wind and solar power. However, such integration requires substantial and rapid improvements to the existing transmission grids. Using a mix of qualitative and quantitative methods, we analysed the opinions and views of stakeholders concerning the main barriers and solutions to this problem. The results suggest two conclusions. The first is that primary barriers to the currently needed level of grid expansion are not technical or financial, but the lack of appropriate regulatory frameworks and public acceptance. The second is that major changes are needed in the overall regulatory process, rather than simply minor modifications or improved implementation of existing regulations. - Highlights: ► Estimations of perceptions on barriers for expansion of electricity grids in Europe. ► Recommendations on political process and level of acceptance among European population. ► Needs for better, simplified and standardized regulations. ► Strong and transparent consultation process in all stages.

  5. Access to Strong Opioid Analgesics in the Context of Legal and Regulatory Barriers in Eleven Central and Eastern European Countries.

    Science.gov (United States)

    Vranken, Marjolein J M; Mantel-Teeuwisse, Aukje K; Schutjens, Marie-Hélène D B; Scholten, Willem K; Jünger, Saskia; Medic, Dr Rer; Leufkens, Hubert G M

    2018-04-06

    In 2011-2013, >95% of the global opioid analgesics consumption occurred in three regions, accounting for 15% of the world population. Despite abundant literature on barriers to access, little is known on the correlation between actual access to opioid analgesics and barriers to access, including legal and regulatory barriers. This study aimed to evaluate the correlation between access to strong opioid analgesics and barriers to access in national legislation and regulations in 11 central and eastern European countries that participated in the Access to Opioid Medication in Europe (ATOME) project. Two variables were contrasted to assess their correlation: the country level of access to strong opioid analgesics indicated by the Adequacy of Consumption Measure (ACM) and the number of potential legal and regulatory barriers identified by an external review of legislation and regulations. A linear correlation was evaluated using a squared linear correlation coefficient. Evaluation of the correlation between the ACM and the number of potential barriers produces an R 2 value of 0.023 and a correlation plot trend line gradient of -0.075, indicating no correlation between access to strong opioid analgesics and the number of potential barriers in national legislation and regulations in the countries studied. No correlation was found, which indicates that other factors besides potential legal and regulatory barriers play a critical role in withholding prescribers and patients essential pain medication in the studied countries. More research is needed toward better understanding of the complex interplay of factors that determine access to strong opioid analgesics.

  6. Lipopolysaccharide-Elicited TSLPR Expression Enriches a Functionally Discrete Subset of Human CD14+ CD1c+ Monocytes.

    Science.gov (United States)

    Borriello, Francesco; Iannone, Raffaella; Di Somma, Sarah; Vastolo, Viviana; Petrosino, Giuseppe; Visconte, Feliciano; Raia, Maddalena; Scalia, Giulia; Loffredo, Stefania; Varricchi, Gilda; Galdiero, Maria Rosaria; Granata, Francescopaolo; Del Vecchio, Luigi; Portella, Giuseppe; Marone, Gianni

    2017-05-01

    Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor (TSLPR) complex, a heterodimer composed of TSLPR and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLPR complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is poorly defined. We demonstrate that TSLP enhances human CD14 + monocyte CCL17 production in response to LPS and IL-4. Surprisingly, only a subset of CD14 + CD16 - monocytes, TSLPR + monocytes (TSLPR + mono), expresses TSLPR complex upon LPS stimulation in an NF-κB- and p38-dependent manner. Phenotypic, functional, and transcriptomic analysis revealed specific features of TSLPR + mono, including higher CCL17 and IL-10 production and increased expression of genes with important immune functions (i.e., GAS6 , ALOX15B , FCGR2B , LAIR1 ). Strikingly, TSLPR + mono express higher levels of the dendritic cell marker CD1c. This evidence led us to identify a subset of peripheral blood CD14 + CD1c + cells that expresses the highest levels of TSLPR upon LPS stimulation. The translational relevance of these findings is highlighted by the higher expression of TSLPR and CD127 mRNAs in monocytes isolated from patients with Gram-negative sepsis compared with healthy control subjects. Our results emphasize a phenotypic and functional heterogeneity in an apparently homogeneous population of human CD14 + CD16 - monocytes and prompt further ontogenetic and functional analysis of CD14 + CD1c + and LPS-activated CD14 + CD1c + TSLPR + mono. Copyright © 2017 by The American Association of Immunologists, Inc.

  7. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    Directory of Open Access Journals (Sweden)

    Lee Na-Young

    2010-08-01

    Full Text Available Abstract Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells, as in vitro blood-placental barrier (BPB model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC activator in TR-TBT cells. Also, calcium ion (Ca2+ was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α, lipopolysaccharide (LPS and diethyl maleate (DEM significantly increased taurine uptake, but H2O2 and nitric oxide (NO donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus.

  8. Analysis of Alcohol Industry Submissions against Marketing Regulation

    Science.gov (United States)

    Martino, Florentine Petronella; Miller, Peter Graeme; Coomber, Kerri; Hancock, Linda; Kypri, Kypros

    2017-01-01

    A growing body of literature points to the role of vested interests as a barrier to the implementation of effective public health policies. Corporate political activity by the alcohol industry is commonly used to influence policy and regulation. It is important for policy makers to be able to critique alcohol industry claims opposed to improved alcohol marketing regulation. The Australian National Preventive Health Agency reviewed alcohol marketing regulations in 2012 and stakeholders were invited to comment on them. In this study we used thematic analysis to examine submissions from the Australian alcohol industry, based on a system previously developed in relation to tobacco industry corporate political activity. The results show that submissions were a direct lobbying tactic, making claims to government that were contrary to the evidence-base. Five main frames were identified, in which the alcohol industry claimed that increased regulation: (1) is unnecessary; (2) is not backed up by sufficient evidence; (3) will lead to unintended negative consequences; and (4) faces legal barriers to implementation; underpinned by the view (5) that the industry consists of socially responsible companies working toward reducing harmful drinking. In contrast with tobacco industry submissions on public policy, which often focused on legal and economic barriers, the Australian alcohol industry placed a heavier emphasis on notions of regulatory redundancy and insufficient evidence. This may reflect differences in where these industries sit on the ‘regulatory pyramid’, alcohol being less regulated than tobacco. PMID:28118411

  9. Analysis of Alcohol Industry Submissions against Marketing Regulation.

    Directory of Open Access Journals (Sweden)

    Florentine Petronella Martino

    Full Text Available A growing body of literature points to the role of vested interests as a barrier to the implementation of effective public health policies. Corporate political activity by the alcohol industry is commonly used to influence policy and regulation. It is important for policy makers to be able to critique alcohol industry claims opposed to improved alcohol marketing regulation. The Australian National Preventive Health Agency reviewed alcohol marketing regulations in 2012 and stakeholders were invited to comment on them. In this study we used thematic analysis to examine submissions from the Australian alcohol industry, based on a system previously developed in relation to tobacco industry corporate political activity. The results show that submissions were a direct lobbying tactic, making claims to government that were contrary to the evidence-base. Five main frames were identified, in which the alcohol industry claimed that increased regulation: (1 is unnecessary; (2 is not backed up by sufficient evidence; (3 will lead to unintended negative consequences; and (4 faces legal barriers to implementation; underpinned by the view (5 that the industry consists of socially responsible companies working toward reducing harmful drinking. In contrast with tobacco industry submissions on public policy, which often focused on legal and economic barriers, the Australian alcohol industry placed a heavier emphasis on notions of regulatory redundancy and insufficient evidence. This may reflect differences in where these industries sit on the 'regulatory pyramid', alcohol being less regulated than tobacco.

  10. Analysis of Alcohol Industry Submissions against Marketing Regulation.

    Science.gov (United States)

    Martino, Florentine Petronella; Miller, Peter Graeme; Coomber, Kerri; Hancock, Linda; Kypri, Kypros

    2017-01-01

    A growing body of literature points to the role of vested interests as a barrier to the implementation of effective public health policies. Corporate political activity by the alcohol industry is commonly used to influence policy and regulation. It is important for policy makers to be able to critique alcohol industry claims opposed to improved alcohol marketing regulation. The Australian National Preventive Health Agency reviewed alcohol marketing regulations in 2012 and stakeholders were invited to comment on them. In this study we used thematic analysis to examine submissions from the Australian alcohol industry, based on a system previously developed in relation to tobacco industry corporate political activity. The results show that submissions were a direct lobbying tactic, making claims to government that were contrary to the evidence-base. Five main frames were identified, in which the alcohol industry claimed that increased regulation: (1) is unnecessary; (2) is not backed up by sufficient evidence; (3) will lead to unintended negative consequences; and (4) faces legal barriers to implementation; underpinned by the view (5) that the industry consists of socially responsible companies working toward reducing harmful drinking. In contrast with tobacco industry submissions on public policy, which often focused on legal and economic barriers, the Australian alcohol industry placed a heavier emphasis on notions of regulatory redundancy and insufficient evidence. This may reflect differences in where these industries sit on the 'regulatory pyramid', alcohol being less regulated than tobacco.

  11. Investing in Energy Efficiency. Removing the Barriers

    International Nuclear Information System (INIS)

    2004-01-01

    Investing in improving energy efficiency has the clear advantages of reducing energy costs, improving security of supply and mitigating the environmental impacts of energy use. And still, many viable opportunities for higher energy efficiency are not tapped because of the existence of numerous barriers to such investments. These lost opportunities imply costs to the individual energy consumers and to the society as a whole and they are particularly important in economies in transition. This report identifies various types of barriers for making energy efficiency investments (be they of legal, administrative, institutional or financial nature), mainly in buildings, district heating and efficient lighting. The role of various bodies and organisations for the facilitation of energy efficiency investments is analysed, from public authorities and regulators to banks and international financing institutions

  12. Glutamate Transporters in the Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Helms, Hans Christian Cederberg; Nielsen, Carsten Uhd; Waagepetersen, Helle S

    2017-01-01

    concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries...... cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux......., regulates the exchange of nutrients, gases, and metabolic waste products between plasma and brain interstitial fluid. It has been suggested that brain capillary endothelial cells could play an important role in L-glutamate homeostasis by mediating brain-to-blood L-glutamate efflux. Both in vitro and in vivo...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  14. Role of intestinal mucosal barrier in the development and progression of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    ZHANG Yuanyuan

    2016-12-01

    Full Text Available The incidence of non-alcoholic fatty liver disease (NAFLD has been increasing year by year in China. Intestinal mucosa is the largest organ for bacterial storage, and intestinal mucosal barrier includes biological barrier, mechanical barrier, immunological barrier, and chemical barrier. This article investigates the important role of intestinal mucosal barrier function in the pathogenesis of NAFLD. As for the intestinal biological barrier, abnormalities in gut microbiota occur earlier than obesity and other metabolic disorders; small intestinal bacterial overgrowth may affect energy metabolism, promote insulin resistance, and get involved in the pathogenesis of NAFLD; regulation of gut microbiota has a certain clinical effect in the treatment of NAFLD. Intestinal mechanical barrier impairment increases the mucosal permeability and is associated with intestinal dysbacteriosis. The changes in intestinal immunological barrier may be associated with obesity, metabolic disorders, and liver inflammation. The changes in intestinal chemical barrier can inhibit the synthesis and secretion of very low-density lipoprotein and low-density lipoprotein in hepatocytes and may result in triglyceride deposition in the liver. It is pointed out that the research on intestinal mucosal barrier function provides promising prospects for the prevention and treatment of NAFLD.

  15. Barriers to the adoption of energy-conserving technologies in the textile industry

    Energy Technology Data Exchange (ETDEWEB)

    Evans, A.R.; Zussman, S.K.

    1979-09-01

    An overview of the textile industry and a discussion of energy-conserving technologies currently available at the pilot-demonstration stage are presented. Existing and potential barriers to the adoption of these technologies in the textile industry identified are: economic; technical acceptance; conflict between commitments of capital for compliance with environmental and health regulations and for investment in energy conservation measures; and a lack of information and technical expertise. Possible measures to eliminate barriers to the implementation of energy-conserving technologies are discussed. (MCW)

  16. CORRIDOR-TYPE BAFFLED MIXING BASIN WITH CROSS POROUS BARRIERS

    Directory of Open Access Journals (Sweden)

    S. M. Epoyan

    2018-02-01

    Full Text Available Purpose. The paper hightlights the increase in operational efficiency of corridor-type baffled mixing basin by installing of cross porous barriers made of gravel (or other materials and epoxy resin, grade ED-20 (ED-16 with the hardener polyethylenepolyamine (PEPA, approved by Ukrainian Ministry of Health in systems of utility and drinking water supply. Methodology. The first stage of the experiments was performed on the model of the proposed mixer in scale 1:4 in order to determine the local resistance of the porous barrier, which is made of gravel with a size of 10-15 mm (average diameter 12.5 mm and thickness of 50 mm. The local resistance of the barrier was measured using piezometers installed before and after the porous barrier. The velocity of water motion in the corridor of the mixer was determined depending on the water consumption, incoming on the mixer accordingly to the water meter and by the volumetric method. Findings. In accordance with researches when the water flows at a velocity of 0.1 m/s in the corridor of the mixer, the head losses in the porous barrier is 17 cm (0.17 m, and at a velocity of 0.2 m/s–0.68 m. The resistance coefficient (ξ, which is equal to 333.2 for the investigated barrier, was determined experimentally. It allows determining the head losses in the porous barrier at other velocities of water motion. When the velocity of water motion in the corridors of the mixer is from 0.7 up to 0.5 m/s, head losses increase almost fourfold. The conducted researches allowed to develop a calculation methodology for corridor-type baffled mixing basin with porous polymer-concrete barriers. Originality. Authors developed and investigated the corridor-type baffled mixing basin with porous polymer-concrete barriers. These barriers allow increasing and regulating the intensity and time of reagents mixing with the initial water exactly in the barriers, improving the distribution of the flow through the section of the mixer

  17. Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects.

    Science.gov (United States)

    Ghosh, Siddhartha S; He, Hongliang; Wang, Jing; Gehr, Todd W; Ghosh, Shobha

    2018-01-02

    Curcumin has anti-inflammatory, anti-oxidant and anti-proliferative properties established largely by in vitro studies. Accordingly, oral administration of curcumin beneficially modulates many diseases including diabetes, fatty-liver disease, atherosclerosis, arthritis, cancer and neurological disorders such as depression, Alzheimer's or Parkinson's disease. However, limited bioavailability and inability to detect curcumin in circulation or target tissues has hindered the validation of a causal role. We established curcumin-mediated decrease in the release of gut bacteria-derived lipopolysaccharide (LPS) into circulation by maintaining the integrity of the intestinal barrier function as the mechanism underlying the attenuation of metabolic diseases (diabetes, atherosclerosis, kidney disease) by curcumin supplementation precluding the need for curcumin absorption. In view of the causative role of circulating LPS and resulting chronic inflammation in the development of diseases listed above, this review summarizes the mechanism by which curcumin affects the several layers of the intestinal barrier and, despite negligible absorption, can beneficially modulate these diseases.

  18. Molecular Pathophysiology of Epithelial Barrier Dysfunction in Inflammatory Bowel Diseases

    Directory of Open Access Journals (Sweden)

    Jessica Y. Lee

    2018-03-01

    Full Text Available Over the years, the scientific community has explored myriads of theories in search of the etiology and a cure for inflammatory bowel disease (IBD. The cumulative evidence has pointed to the key role of the intestinal barrier and the breakdown of these mechanisms in IBD. More and more scientists and clinicians are embracing the concept of the impaired intestinal epithelial barrier and its role in the pathogenesis and natural history of IBD. However, we are missing a key tool that bridges these scientific insights to clinical practice. Our goal is to overcome the limitations in understanding the molecular physiology of intestinal barrier function and develop a clinical tool to assess and quantify it. This review article explores the proteins in the intestinal tissue that are pivotal in regulating intestinal permeability. Understanding the molecular pathophysiology of impaired intestinal barrier function in IBD may lead to the development of a biochemical method of assessing intestinal tissue integrity which will have a significant impact on the development of novel therapies targeting the intestinal mucosa.

  19. Considerations in the development of subsurface containment barrier performance standards

    International Nuclear Information System (INIS)

    Dunstan, S.; Zdinak, A.P.; Lodman, D.

    1997-01-01

    The U.S. Department of Energy (DOE) is supporting subsurface barriers as an alternative remedial option for management of contamination problems at their facilities. Past cleanup initiatives have sometimes proven ineffective or extremely expensive. Economic considerations coupled with changing public and regulatory philosophies regarding remediation techniques makes subsurface barriers a promising technology for future cleanup efforts. As part of the initiative to develop subsurface containment barriers as an alternative remedial option, DOE funded MSE Technology Applications, Inc. (MSE) to conduct a comprehensive review to identify performance considerations for the acceptability of subsurface barrier technologies as a containment method. Findings from this evaluation were intended to provide a basis for selection and application of containment technologies to address waste problems at DOE sites. Based on this study, the development of performance standards should consider: (1) sustainable low hydraulic conductivity; (2) capability to meet applicable regulations; (3) compatibility with subsurface environmental conditions; (4) durability and long-term stability; (5) repairability; and (6) verification and monitoring. This paper describes the approach for determining considerations for performance standards

  20. Overcoming Barriers between Volunteer Professionals Advising Project-Based Learning Teams with Regulation Tools

    Science.gov (United States)

    Rees Lewis, Daniel G.; Easterday, Matthew W.; Harburg, Emily; Gerber, Elizabeth M.; Riesbeck, Christopher K.

    2018-01-01

    To provide the substantial support required for project-based learning (PBL), educators can incorporate professional experts as "design coaches." However, previous work shows barriers incorporating design coaches who can rarely meet face-to-face: (1) communication online is time-consuming, (2) updating coaches online is not perceived as…

  1. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-05-06

    Various methods and systems are provided for smart parking barriers. In one example, among others, a smart parking barrier system includes a movable parking barrier located at one end of a parking space, a barrier drive configured to control positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking space and a second position that allows access to the parking space. The parking controller can initiate movement of the movable parking barrier in response to a positive identification of an individual allowed to use the parking space. The parking controller can identify the individual through, e.g., a RFID tag, a mobile device (e.g., a remote control, smartphone, tablet, etc.), an access card, biometric information, or other appropriate identifier.

  2. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

    Directory of Open Access Journals (Sweden)

    Michael K DeSalvo

    2014-11-01

    Full Text Available AbstractCentral nervous system (CNS function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with FACS and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ABC and SLC transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  3. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

    Science.gov (United States)

    DeSalvo, Michael K; Hindle, Samantha J; Rusan, Zeid M; Orng, Souvinh; Eddison, Mark; Halliwill, Kyle; Bainton, Roland J

    2014-01-01

    Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with fluorescence activated cell sorting (FACS) and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ATP-binding cassette (ABC) and solute carrier (SLC) transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  4. Splenectomy attenuates severe thermal trauma-induced intestinal barrier breakdown in rats.

    Science.gov (United States)

    Liu, Xiang-dong; Chen, Zhen-yong; Yang, Peng; Huang, Wen-guang; Jiang, Chun-fang

    2015-12-01

    The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane-associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all PSplenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all PSplenectomy may provide a therapeutic benefit in restoring burn-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.

  5. Regulatory barriers to hazardous waste technology innovation

    International Nuclear Information System (INIS)

    Kuusinen, T.L.; Siegel, M.R.

    1991-02-01

    The primary federal regulatory programs that influence the development of new technology for hazardous waste are the Resource Conservation and Recovery Act (RCRA) and the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA, also commonly known as Superfund). Two important aspects of RCRA that can create barriers to hazardous waste technology innovation are technology-based waste pre-treatment standards and a cumbersome permitting program. By choosing a technology-based approach to the RCRA land disposal restrictions program, the US Environmental Protection Agency (EPA) has simultaneously created tremendous demand for the technologies specified in its regulations, while at the same time significantly reduced incentives for technology innovation that might have otherwise existed. Also, the RCRA hazardous waste permitting process can take years and cost hundreds of thousands of dollars. The natural tendency of permit writers to be cautious of unproven (i.e., innovative) technology also can create a barrier to deployment of new technologies. EPA has created several permitting innovations, however, to attempt to mitigate this latter barrier. Understanding the constraints of these permitting innovations can be important to the success of hazardous waste technology development programs. 3 refs

  6. Chaotic correlations in barrier billiards with arbitrary barriers

    International Nuclear Information System (INIS)

    Osbaldestin, A H; Adamson, L N C

    2013-01-01

    We study autocorrelation functions in symmetric barrier billiards for golden mean trajectories with arbitrary barriers. Renormalization analysis reveals the presence of a chaotic invariant set and thus that, for a typical barrier, there are chaotic correlations. The chaotic renormalization set is the analogue of the so-called orchid that arises in a generalized Harper equation. (paper)

  7. Numerical assessment of conventional regulation effectiveness for ...

    African Journals Online (AJOL)

    ... depends on fire safety engineering that is provided, and which is generally established using smoke spread field and temperature distribution predictions. ... conventional regulation; ventilation strategies; smoke temperature; smoke barriers ...

  8. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes

    OpenAIRE

    DeSalvo, Michael K.; Hindle, Samantha J.; Rusan, Zeid M.; Orng, Souvinh; Eddison, Mark; Halliwill, Kyle; Bainton, Roland J.

    2014-01-01

    Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; ...

  9. Overexpression of Hypoxia-Inducible Factor-1α Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia

    Directory of Open Access Journals (Sweden)

    Pei Wang

    2013-09-01

    Full Text Available Background/Aims: The mechanisms involved in endothelial barrier dysfunction induced by hypoxia are incompletely understood. There is debate about the role of hypoxia-inducible factor-1α (HIF-1α in endothelial barrier disruption. The aim of this study was to investigate the effect of genetic overexpression of HIF-1α on barrier function and the underlying mechanisms in hypoxic endothelial cells. Methods: The plasmid pcDNA3.1/V5-His-HIF-1α was stably transfected into human endothelial cells. The cells were exposed to normoxia or hypoxia. The mRNA and protein expressions of HIF-1α were detected by RT-PCR and Western blot respectively. The barrier function was assessed by measuring the transendothelial electrical resistance (TER. The Western blot analysis was used to determine the protein expression of glucose transporter-1 (GLUT-1, zonular occludens-1 (ZO-1, occludin, and myosin light chain kinase (MLCK in endothelial cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR. Results: Genetic overexpression of HIF-1α significantly increased the mRNA and protein expression of HIF-1α in endothelial cells. The overexpression of HIF-1α enhanced the hypoxia-induced increase of HIF-1α and GLUT-1 protein expression. HIF-1α overexpression not only exacerbated hypoxia-induced endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation of MLCK protein expression. HIF-1α overexpression also enhanced IL-1β, IL-6 and TNF-α mRNA expression. Conclusion: We provide evidence that genetic overexpression of HIF-1α aggravates the hypoxia-induced endothelial barrier dysfunction via enhancing the up-regulation of MLCK protein expression caused by hypoxia, suggesting a potential role for HIF-1α in the pathogenesis of endothelial barrier dysfunction in hypoxia.

  10. Krüppel-like factor 5 is essential for maintenance of barrier function in mouse colon.

    Science.gov (United States)

    Liu, Yang; Chidgey, Martyn; Yang, Vincent W; Bialkowska, Agnieszka B

    2017-11-01

    Krüppel-like factor 5 (KLF5) is a member of the zinc finger family of transcription factors that regulates homeostasis of the intestinal epithelium. Previous studies suggested an indispensable role of KLF5 in maintaining intestinal barrier function. In the current study, we investigated the mechanisms by which KLF5 regulates colonic barrier function in vivo and in vitro. We used an inducible and a constitutive intestine-specific Klf5 knockout mouse models ( Villin-CreER T2 ;Klf5 fl/fl designated as Klf5 ΔIND and Villin-Cre;Klf5 fl/fl as Klf5 ΔIS ) and studied an inducible KLF5 knockdown in Caco-2 BBe cells using a lentiviral Tet-on system (Caco-2 BBe KLF5ΔIND ). Specific knockout of Klf5 in colonic tissues, either inducible or constitutive, resulted in increased intestinal permeability. The phenotype was accompanied by a significant reduction in Dsg2 , which encodes desmoglein-2, a desmosomal cadherin, at both mRNA and protein levels. Transmission electron microscopy showed alterations of desmosomal morphology in both KLF5 knockdown Caco-2 BBe cells and Klf5 knockout mouse colonic tissues. Inducible knockdown of KLF5 in Caco-2BBe cells grown on Transwell plates led to impaired barrier function as evidenced by decreased transepithelial electrical resistance and increased paracellular permeability to fluorescein isothiocyanate-4 kDa dextran. Furthermore, DSG2 was significantly decreased in KLF5 knockdown cells, and DSG2 overexpression partially rescued the impaired barrier function caused by KLF5 knockdown. Electron microscopy studies demonstrated altered desmosomal morphology after KLF5 knockdown. In combination with chromatin immunoprecipitation analysis and promoter study, our data show that KLF5 regulates intestinal barrier function by mediating the transcription of DSG2 , a gene encoding a major component of desmosome structures. NEW & NOTEWORTHY The study is original research on the direct function of a Krüppel-like factor on intestinal barrier function

  11. External and Internal Barriers to Studying Can Affect Student Success and Retention in a Diverse Classroom

    Directory of Open Access Journals (Sweden)

    Laurence Clement

    2016-12-01

    Full Text Available Although a majority of under-represented minority (URM students begin their postsecondary education at community colleges, little is known about barriers to success and retention for transfer-bound science students. This study focuses on some of the barriers that affect these students’ ability to study adequately for a community college “gateway” course. It tests whether instructors’ expectations of study time were realistic for community college students and whether students reported facing external barriers, such as job and family responsibilities, or internal barriers to studying, such as lack of motivational, cognitive, and metacognitive abilities, all of which have been shown to impact academic success and retention. It also tests whether students who faced such barriers were less likely to succeed in and complete the course, as well as whether time spent studying was related to course success. The findings reported here show that community college students do not have enough available time to study and that external and internal barriers are both prevalent among these students. In addition, students who faced such barriers are more likely to fail or drop the class. Results also show that study time is positively correlated with retention, but not performance, as well as with some motivational, cognitive, and metacognitive dimensions of self-regulated learning. These findings lead to new questions, including whether student success in a community college class is associated with the use of cognitive and metacognitive learning strategies for students with no prior degrees, and whether increased course structure may improve success for college students with lower self-regulated abilities.

  12. Identifying and overcoming barriers to technology implementation

    International Nuclear Information System (INIS)

    Bailey, M.; Warren, S.; McCune, M.

    1996-01-01

    In a recent General Accounting Office report, the Department of Energy's (DOE) Office of Environmental Management was found to be ineffective in integrating their environmental technology development efforts with the cleanup actions. As a result of these findings, a study of remediation documents was performed by the Technology Applications Team within DOE's Office of Environmental Restoration (EM-40) to validate this finding and to understand why it was occurring. A second initiative built on the foundation of the remediation document study and evaluated solutions to the ineffective implementation of improved technologies. The Technology Applications Team examined over 50 remediation documents (17 projects) which included nearly 600 proposed remediation technologies. It was determined that very few technologies are reaching the Records of Decision documents. In fact, most are eliminated in the early stages of consideration. These observations stem from regulators' and stakeholders' uncertainties in cost and performance of the technology and the inability of the technology to meet site specific conditions. The Technology Applications Team also set out to identify and evaluate solutions to barriers to implementing innovative technology into the DOE's environmental management activities. Through the combined efforts of DOE and the Hazardous Waste Action Coalition (HWAC), a full day workshop was conducted at the annual HWAC meeting in June 1995 to solve barriers to innovative technology implementation. Three barriers were identified as widespread throughout the DOE complex and industry. Identified barriers included a lack of verified or certified cost and performance data for innovative technologies; risk of failure to reach cleanup goals using innovative technologies; and communication barriers that are present at virtually every stage of the characterization/remediation process from development through implementation

  13. Barriers to clinical adoption of next generation sequencing: Perspectives of a policy Delphi panel

    Directory of Open Access Journals (Sweden)

    Donna A. Messner

    2016-09-01

    Full Text Available This research aims to inform policymakers by engaging expert stakeholders to identify, prioritize, and deliberate the most important and tractable policy barriers to the clinical adoption of next generation sequencing (NGS. A 4-round Delphi policy study was done with a multi-stakeholder panel of 48 experts. The first 2 rounds of online questionnaires (reported here assessed the importance and tractability of 28 potential barriers to clinical adoption of NGS across 3 major policy domains: intellectual property, coverage and reimbursement, and FDA regulation. We found that: 1 proprietary variant databases are seen as a key challenge, and a potentially intractable one; 2 payer policies were seen as a frequent barrier, especially a perceived inconsistency in standards for coverage; 3 relative to other challenges considered, FDA regulation was not strongly perceived as a barrier to clinical use of NGS. Overall the results indicate a perceived need for policies to promote data-sharing, and a desire for consistent payer coverage policies that maintain reasonably high standards of evidence for clinical utility, limit testing to that needed for clinical care decisions, and yet also flexibly allow for clinician discretion to use genomic testing in uncertain circumstances of high medical need.

  14. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-01-01

    positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking

  15. On the influence of the European trade barrier on the chinese pv industry: Is the solution to the solar-dispute “successful”?

    International Nuclear Information System (INIS)

    McCarthy, Killian J.

    2016-01-01

    In July 2013 the European Union (EU) imposed restrictions on Chinese solar photovoltaic (PV) manufacturers, looking to exporting to the EU. In this paper, we consider the impact of this trade barrier, using a sample of 454 stock-listed PV producing firms. We find that the trade barrier erased US$ 8,19 million off the value of the average European PV manufacturers and US$ 247.03 million off the value of the average Chinese PV manufacturers. We also find that while the trade barrier reduced the willingness of the industry to reorganise, it stimulates Chinese manufacturers to reorganise both their domestic and their international operations. The latter, we warn, is likely an attempt by Chinese manufacturers to ‘tariff jump’. We conclude, therefore, that the trade barrier was both inefficient, in that it both hurt the companies it aimed to protect, and ineffective, as those it sought to punish may have circumvented it. - Highlights: • Consider the impact of EU trade restrictions on 454 PV producing firms. • Show that the regulation wiped $8 m off the average European PV manufacturer. • Show that the regulation wiped US$247 m off the value of the average Chinese PV manufacturers. • Show that the regulation stimulated Chinese firms to circumvent the barrier. • Conclude that the trade barrier was inefficient and ineffective.

  16. Stability of barrier buckets with zero RF-barrier separations

    Energy Technology Data Exchange (ETDEWEB)

    Ng, K.Y.; /Fermilab

    2005-03-01

    A barrier bucket with very small separation between the rf barriers (relative to the barrier widths) or even zero separation has its synchrotron tune decreasing rather slowly from a large value towards the boundary of the bucket. As a result, large area at the bucket edges can become unstable under the modulation of rf voltage and/or rf phase. In addition, chaotic regions may form near the bucket center and extend outward under increasing modulation. Application is made to those barrier buckets used in the process of momentum mining at the Fermilab Recycler Ring.

  17. Extending the frontiers of employment regulation:

    African Journals Online (AJOL)

    UWC

    role, as it were, by the coincidence of their class, race and gender. In this sense ..... especially women) to be employed in the formal economy, domestic work remains ..... greatest barrier to more effective regulation in a sector such as this.

  18. Market and Policy Barriers for Demand Response Providing Ancillary Services in U.S. Markets

    Energy Technology Data Exchange (ETDEWEB)

    Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); MacDonald, Jason [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Goldman, Charles [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2013-03-01

    In this study, we attempt to provide a comprehensive examination of various market and policy barriers to demand response providing ancillary services in both ISO/RTO and non-ISO/RTO regions, especially at the program provider level. It is useful to classify barriers in order to create a holistic understanding and identify parties that could be responsible for their removal. This study develops a typology of barriers focusing on smaller customers that must rely on a program provider (i.e., electric investor owned utility or IOU, ARC) to create an aggregated DR resource in order to bring ancillary services to the balancing authority.ii The barriers were identified through examinations of regulatory structures, market environments, and product offerings; and discussions with industry stakeholders and regulators. In order to help illustrate the differences in barriers among various wholesale market designs and their constituent retail environments, four regions were chosen to use as case studies: Colorado, Texas, Wisconsin, and New Jersey. We highlight the experience in each area as it relates to the identified barriers.

  19. Mesenchymal Stem Cells Regulate Blood Brain Barrier Integrity in Traumatic Brain Injury Through Production of the Soluble Factor TIMP3

    Science.gov (United States)

    Menge, Tyler; Zhao, Yuhai; Zhao, Jing; Wataha, Kathryn; Geber, Michael; Zhang, Jianhu; Letourneau, Phillip; Redell, John; Shen, Li; Wang, Jing; Peng, Zhalong; Xue, Hasen; Kozar, Rosemary; Cox, Charles S.; Khakoo, Aarif Y.; Holcomb, John B.; Dash, Pramod K.; Pati, Shibani

    2013-01-01

    Mesenchymal stem cells (MCSs) have been shown to have therapeutic potential in multiple disease states associated with vascular instability including traumatic brain injury (TBI). In the present study, Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) is identified as the soluble factor produced by MSCs that can recapitulate the beneficial effects of MSCs on endothelial function and blood brain barrier (BBB) compromise in TBI. Attenuation of TIMP3 expression in MSCs completely abrogates the effect of MSCs on BBB permeability and stability, while intravenous administration of rTIMP3 alone can inhibit BBB permeability in TBI. Our results demonstrate that MSCs increase circulating levels of soluble TIMP3, which inhibits VEGF-A induced breakdown of endothelial AJs in vitro and in vivo. These findings elucidate a clear molecular mechanism for the effects of MSCs on the BBB in TBI, and directly demonstrate a role for TIMP3 in regulation of BBB integrity. PMID:23175708

  20. Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.

    Science.gov (United States)

    Benedicto, Ignacio; Lehmann, Guillermo L; Ginsberg, Michael; Nolan, Daniel J; Bareja, Rohan; Elemento, Olivier; Salfati, Zelda; Alam, Nazia M; Prusky, Glen T; Llanos, Pierre; Rabbany, Sina Y; Maminishkis, Arvydas; Miller, Sheldon S; Rafii, Shahin; Rodriguez-Boulan, Enrique

    2017-05-19

    The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch's membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Transcriptome analyses show that expression of extracellular matrix-related genes changes dramatically over this period. Co-culture experiments support the existence of a novel regulatory pathway: ECs secrete factors that remodel RPE basement membrane, and integrin receptors sense these changes triggering Rho GTPase signals that modulate RPE tight junctions and enhance RPE barrier function. We anticipate our results will spawn a search for additional roles of choroid ECs in RPE physiology and disease.

  1. Market and policy barriers for demand response providing ancillary services in U.S. markets

    Energy Technology Data Exchange (ETDEWEB)

    Cappers, Peter [Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); MacDonald, Jason [Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States); Goldman, Charles [Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

    2013-03-01

    This study provides an examination of various market and policy barriers to demand response providing ancillary services in both ISO/RTO and non-ISO/RTO regions, especially at the program provider level. It is useful to classify barriers in order to create a holistic understanding and identify parties that could be responsible for their removal. This study develops a typology of barriers focusing on smaller customers that must rely on a program provider (i.e., electric investor owned utility or IOU, ARC) to create an aggregated DR resource in order to bring ancillary services to the balancing authority. The barriers were identified through examinations of regulatory structures, market environments, and product offerings; and discussions with industry stakeholders and regulators. In order to help illustrate the differences in barriers among various wholesale market designs and their constituent retail environments, four regions were chosen to use as case studies: Colorado, Texas, Wisconsin, and New Jersey.

  2. Lactobacillus frumenti Facilitates Intestinal Epithelial Barrier Function Maintenance in Early-Weaned Piglets

    Science.gov (United States)

    Hu, Jun; Chen, Lingli; Zheng, Wenyong; Shi, Min; Liu, Liu; Xie, Chunlin; Wang, Xinkai; Niu, Yaorong; Hou, Qiliang; Xu, Xiaofan; Xu, Baoyang; Tang, Yimei; Zhou, Shuyi; Yan, Yiqin; Yang, Tao; Ma, Libao; Yan, Xianghua

    2018-01-01

    Increased intestinal epithelial barrier function damages caused by early weaning stress have adverse effects on swine health and feed utilization efficiency. Probiotics have emerged as the promising antibiotic alternatives used for intestinal barrier function damage prevention. Our previous data showed that Lactobacillus frumenti was identified as a predominant Lactobacillus in the intestinal microbiota of weaned piglets. However, whether the intestinal epithelial barrier function in piglets was regulated by L. frumenti is still unclear. Here, piglets received a PBS vehicle or PBS suspension (2 ml, 108 CFU/ml) containing the L. frumenti by oral gavage once a day during the period of 6–20 days of age prior to early weaning. Our data demonstrated that oral administration of L. frumenti significantly improved the intestinal mucosal integrity and decreased the serum endotoxin and D-lactic acid levels in early-weaned piglets (26 days of age). The intestinal tight junction proteins (including ZO-1, Occludin, and Claudin-1) were significantly up-regulated by L. frumenti administration. The serum immunoglobulin G (IgG) levels, intestinal secretory immunoglobulin A (sIgA) levels, and interferon-γ (IFN-γ) levels were significantly increased by L. frumenti administration. Furthermore, our data revealed that oral administration of L. frumenti significantly increased the relative abundances of health-promoting microbes (including L. frumenti, Lactobacillus gasseri LA39, Parabacteroides distasonis, and Kazachstania telluris) and decreased the relative abundances of opportunistic pathogens (including Desulfovibrio desulfuricans and Candida humilis). Functional alteration of the intestinal bacterial community by L. frumenti administration was characterized by the significantly increased fatty acids and protein metabolism and decreased diseases-associated metabolic pathways. These findings suggest that L. frumenti facilitates intestinal epithelial barrier function maintenance

  3. SH2 domain-containing protein tyrosine phosphatase 2 and focal adhesion kinase protein interactions regulate pulmonary endothelium barrier function.

    Science.gov (United States)

    Chichger, Havovi; Braza, Julie; Duong, Huetran; Harrington, Elizabeth O

    2015-06-01

    Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized. To assess whether SHP2 activity mediates protection against edema in the endothelium, we assessed the effect of molecular activation of SHP2 on lung endothelial barrier function in response to the edemagenic agents LPS and thrombin. Both LPS and thrombin reduced SHP2 activity, correlated with decreased focal adhesion kinase (FAK) phosphorylation (Y(397) and Y(925)) and diminished SHP2 protein-protein associations with FAK. Overexpression of constitutively active SHP2 (SHP2(D61A)) enhanced baseline endothelial monolayer resistance and completely blocked LPS- and thrombin-induced permeability in vitro and significantly blunted pulmonary edema formation induced by either endotoxin (LPS) or Pseudomonas aeruginosa exposure in vivo. Chemical inhibition of FAK decreased SHP2 protein-protein interactions with FAK concomitant with increased permeability; however, overexpression of SHP2(D61A) rescued the endothelium and maintained FAK activity and FAK-SHP2 protein interactions. Our data suggest that SHP2 activation offers the pulmonary endothelium protection against barrier permeability mediators downstream of the FAK signaling pathway. We postulate that further studies into the promotion of SHP2 activation in the pulmonary endothelium may offer a therapeutic approach for patients

  4. Barriers to Self-Management Behaviors in College Students with Food Allergies

    Science.gov (United States)

    Duncan, Sarah E.; Annunziato, Rachel A.

    2018-01-01

    Objective: This study examined barriers to engagement in self-management behaviors among food-allergic college students (1) within the frameworks of the health belief model (HBM) and common sense self-regulation model (CS-SRM) and (2) in the context of overall risky behaviors. Participants: Undergraduate college students who reported having a…

  5. Safety- barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2008-01-01

    Safety-barrier diagrams and the related so-called 'bow-tie' diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation of safety-barrier diagrams to other methods such as fault...... trees and Bayesian networks is discussed. A simple method for quantification of safety-barrier diagrams is proposed. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk analysis with operational safety management....

  6. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2007-01-01

    Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk...... analysis with operational safety management....

  7. Sex-specific signaling in the blood-brain barrier is required for male courtship in Drosophila.

    Directory of Open Access Journals (Sweden)

    Valbona Hoxha

    Full Text Available Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood-brain barrier (bbb to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood-brain barrier is necessary and that male-specific factors in the bbb are physiologically required for normal male courtship behavior. Feminization of the bbb of adult males significantly reduces male courtship. We show that the bbb-specific G-protein coupled receptor moody and bbb-specific Go signaling in adult males are necessary for normal courtship. These data identify sex-specific factors and signaling processes in the bbb as important regulators of male mating behavior.

  8. Vehicle barrier systems

    International Nuclear Information System (INIS)

    Sena, P.A.

    1986-01-01

    The ground vehicle is one of the most effective tools available to an adversary force. Vehicles can be used to penetrate many types of perimeter barriers, transport equipment and personnel rapidly over long distances, and deliver large amounts of explosives directly to facilities in suicide missions. The function of a vehicle barrier system is to detain or disable a defined threat vehicle at a selected distance from a protected facility. Numerous facilities are installing, or planning to install, vehicle barrier systems and many of these facilities are requesting guidance to do so adequately. Therefore, vehicle barriers are being evaluated to determine their stopping capabilities so that systems can be designed that are both balanced and capable of providing a desired degree of protection. Equally important, many of the considerations that should be taken into account when establishing a vehicle barrier system have been identified. These considerations which pertain to site preparation, barrier selection, system integration and operation, and vehicle/barrier interaction, are discussed in this paper

  9. Assessment of institutional barriers to the use of natural gas fuel in automotive vehicle fleets

    Science.gov (United States)

    Jablonski, J.; Lent, L.; Lawrence, M.; White, L.

    1983-01-01

    Institutional barriers to the use of natural gas as a fuel for motor vehicle fleets were identified. Recommendations for barrier removal were developed. Eight types of institutional barriers were assessed: (1) lack of a national standard for the safe design and certification of natural gas vehicles and refueling stations; (2) excessively conservative or misapplied state and local regulations, including bridge and tunnel restrictions, restrictions on types of vehicles that may be fueled by natural gas, zoning regulations that prohibit operation of refueling stations, parking restrictions, application of LPG standards to LNG vehicles, and unintentionally unsafe vehicle or refueling station requirements; (3) need for clarification of EPA's tampering enforcement policy; (4) the U.S. hydrocarbon standard; (5) uncertainty concerning state utility commission jurisdiction; (6) sale for resale prohibitions imposed by natural gas utility companies or state utility commissions; (7) uncertainty of the effects of conversions to natural gas on vehicle manufactures warranties; and (8) need for a natural gas to gasoline equivalent units conversion factor for use in calculation of state road use taxes.

  10. Load management for refrigeration systems: Potentials and barriers

    Energy Technology Data Exchange (ETDEWEB)

    Grein, Arne, E-mail: a.grein@tu-berlin.de [University of Technology Berlin, Institute for Energy Technology, Department of Energy Systems, Einsteinufer 25 (TA8), 10587 Berlin (Germany); Pehnt, Martin [Institute for Energy and Environmental Research Heidelberg (ifeu), Wilckensstr. 3, 69120 Heidelberg (Germany)

    2011-09-15

    As a strategy to deal with the increasing intermittent input of renewable energy sources in Germany, the adaptation of power consumption is complementary to power-plant regulation, grid expansion and physical energy storage. One demand sector that promises strong returns for load management efforts is cooling and refrigeration. In these processes, thermal inertia provides a temporal buffer for shifting and adjusting the power consumption of cooling systems. We have conducted an empirical investigation to obtain a detailed and time-resolved bottom-up analysis of load management for refrigeration systems in the city of Mannheim, Germany. We have extrapolated our results to general conditions in Germany. Several barriers inhibit the rapid adoption of load management strategies for cooling systems, including informational barriers, strict compliance with legal cooling requirements, liability issues, lack of technical experience, an inadequate rate of return and organizational barriers. Small commercial applications of refrigeration in the food-retailing and cold storage in hotels and restaurants are particularly promising starting points for intelligent load management. When our results are applied to Germany, suitable sectors for load management have theoretical and achievable potential values of 4.2 and 2.8 GW, respectively, amounting to about 4-6% of the maximum power demand in Germany. - Highlights: > Potential and barriers for implementation of load shifting for refrigeration. > Empirical investigation for time-resolved bottom-up analysis in Mannheim, Germany. > Suitable sectors and further recommendations for introducing load management.> Extrapolation of results from local to national level.

  11. Load management for refrigeration systems: Potentials and barriers

    International Nuclear Information System (INIS)

    Grein, Arne; Pehnt, Martin

    2011-01-01

    As a strategy to deal with the increasing intermittent input of renewable energy sources in Germany, the adaptation of power consumption is complementary to power-plant regulation, grid expansion and physical energy storage. One demand sector that promises strong returns for load management efforts is cooling and refrigeration. In these processes, thermal inertia provides a temporal buffer for shifting and adjusting the power consumption of cooling systems. We have conducted an empirical investigation to obtain a detailed and time-resolved bottom-up analysis of load management for refrigeration systems in the city of Mannheim, Germany. We have extrapolated our results to general conditions in Germany. Several barriers inhibit the rapid adoption of load management strategies for cooling systems, including informational barriers, strict compliance with legal cooling requirements, liability issues, lack of technical experience, an inadequate rate of return and organizational barriers. Small commercial applications of refrigeration in the food-retailing and cold storage in hotels and restaurants are particularly promising starting points for intelligent load management. When our results are applied to Germany, suitable sectors for load management have theoretical and achievable potential values of 4.2 and 2.8 GW, respectively, amounting to about 4-6% of the maximum power demand in Germany. - Highlights: → Potential and barriers for implementation of load shifting for refrigeration. → Empirical investigation for time-resolved bottom-up analysis in Mannheim, Germany. → Suitable sectors and further recommendations for introducing load management.→ Extrapolation of results from local to national level.

  12. Barriers to fusion

    International Nuclear Information System (INIS)

    Berriman, A.C.; Butt, R.D.; Dasgupta, M.; Hinde, D.J.; Morton, C.R.; Newton, J.O.

    1999-01-01

    The fusion barrier is formed by the combination of the repulsive Coulomb and attractive nuclear forces. Recent research at the Australian National University has shown that when heavy nuclei collide, instead of a single fusion barrier, there is a set of fusion barriers. These arise due to intrinsic properties of the interacting nuclei such deformation, rotations and vibrations. Thus the range of barrier energies depends on the properties of both nuclei. The transfer of matter between nuclei, forming a neck, can also affect the fusion process. High precision data have been used to determine fusion barrier distributions for many nuclear reactions, leading to new insights into the fusion process

  13. Extremal surface barriers

    International Nuclear Information System (INIS)

    Engelhardt, Netta; Wall, Aron C.

    2014-01-01

    We present a generic condition for Lorentzian manifolds to have a barrier that limits the reach of boundary-anchored extremal surfaces of arbitrary dimension. We show that any surface with nonpositive extrinsic curvature is a barrier, in the sense that extremal surfaces cannot be continuously deformed past it. Furthermore, the outermost barrier surface has nonnegative extrinsic curvature. Under certain conditions, we show that the existence of trapped surfaces implies a barrier, and conversely. In the context of AdS/CFT, these barriers imply that it is impossible to reconstruct the entire bulk using extremal surfaces. We comment on the implications for the firewall controversy

  14. Regulatory analysis for the use of underground barriers at the Hanford Site tank farms

    International Nuclear Information System (INIS)

    Hampsten, K.L.

    1994-01-01

    Sixty-seven of the single-shell tanks at the Hanford Site, Richland, Washington, are assumed to have leaked in the past. Some of the waste retrieval options being considered, such as past-practice sluicing (a process that uses hot water to dislodge waste for subsequent removal by pumping), have the potential for increasing releases of dangerous waste from these tanks. Underground barrier systems are being evaluated as a method to mitigate releases of tank waste to the soil and groundwater that may occur during retrieval activities. The following underground barrier system options are among those being evaluated to determine whether their construction at the Single-Shell Tank Farms is viable. (1) A desiccant barrier would be created by circulating air through the subsurface soil to lower and then maintain the water saturation below the levels required for liquids to flow. (2) An injected materials barrier would be created by injecting materials such as grout or silica into the subsurface soils to form a barrier around and under a given tank or tank farm. (3) A cryogenic barrier would be created by freezing subsurface soils in the vicinity of a tank or tank farm. An analysis is provided of the major regulatory requirements that may impact full scale construction and operation of an underground barrier system and a discussion of factors that should be considered throughout the barrier selection process, irrespective of the type of underground barrier system being considered. However, specific barrier systems will be identified when a given regulation will have significant impact on a particular type of barrier technology. Appendix A provides a matrix of requirements applicable to construction and operation of an underground barrier system

  15. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall.

    Science.gov (United States)

    Fasano, Alessio

    2008-11-01

    The anatomical and functional arrangement of the gastrointestinal tract suggests that this organ, beside its digestive and absorptive functions, regulates the trafficking of macromolecules between the environment and the host through a barrier mechanism. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions, structures whose physiological modulation is mediated by, among others, the recently described protein zonulin. To prevent harm and minimize inflammation, the same paracellular pathway, in concert with the gut-associated lymphoid tissue and the neuroendocrine network, controls the equilibrium between tolerance and immunity to nonself antigens. The zonulin pathway has been exploited to deliver drugs, macromolecules, or vaccines that normally would not be absorbed through the gastrointestinal mucosal barrier. However, if the tightly regulated trafficking of macromolecules is jeopardized secondary to prolonged zonulin up-regulation, the excessive flow of nonself antigens in the intestinal submucosa can cause both intestinal and extraintestinal autoimmune disorders in genetically susceptible individuals. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier competency. Understanding the role of zonulin-dependent intestinal barrier dysfunction in the pathogenesis of autoimmune diseases is an area of translational research that encompasses many fields.

  16. Protein kinase C-dependent signaling controls the midgut epithelial barrier to malaria parasite infection in anopheline mosquitoes.

    Directory of Open Access Journals (Sweden)

    Nazzy Pakpour

    Full Text Available Anopheline mosquitoes are the primary vectors of parasites in the genus Plasmodium, the causative agents of malaria. Malaria parasites undergo a series of complex transformations upon ingestion by the mosquito host. During this process, the physical barrier of the midgut epithelium, along with innate immune defenses, functionally restrict parasite development. Although these defenses have been studied for some time, the regulatory factors that control them are poorly understood. The protein kinase C (PKC gene family consists of serine/threonine kinases that serve as central signaling molecules and regulators of a broad spectrum of cellular processes including epithelial barrier function and immunity. Indeed, PKCs are highly conserved, ranging from 7 isoforms in Drosophila to 16 isoforms in mammals, yet none have been identified in mosquitoes. Despite conservation of the PKC gene family and their potential as targets for transmission-blocking strategies for malaria, no direct connections between PKCs, the mosquito immune response or epithelial barrier integrity are known. Here, we identify and characterize six PKC gene family members--PKCδ, PKCε, PKCζ, PKD, PKN, and an indeterminate conventional PKC--in Anopheles gambiae and Anopheles stephensi. Sequence and phylogenetic analyses of the anopheline PKCs support most subfamily assignments. All six PKCs are expressed in the midgut epithelia of A. gambiae and A. stephensi post-blood feeding, indicating availability for signaling in a tissue that is critical for malaria parasite development. Although inhibition of PKC enzymatic activity decreased NF-κB-regulated anti-microbial peptide expression in mosquito cells in vitro, PKC inhibition had no effect on expression of a panel of immune genes in the midgut epithelium in vivo. PKC inhibition did, however, significantly increase midgut barrier integrity and decrease development of P. falciparum oocysts in A. stephensi, suggesting that PKC

  17. Optimal design of wind barriers using 3D computational fluid dynamics simulations

    Science.gov (United States)

    Fang, H.; Wu, X.; Yang, X.

    2017-12-01

    Desertification is a significant global environmental and ecological problem that requires human-regulated control and management. Wind barriers are commonly used to reduce wind velocity or trap drifting sand in arid or semi-arid areas. Therefore, optimal design of wind barriers becomes critical in Aeolian engineering. In the current study, we perform 3D computational fluid dynamics (CFD) simulations for flow passing through wind barriers with different structural parameters. To validate the simulation results, we first inter-compare the simulated flow field results with those from both wind-tunnel experiments and field measurements. Quantitative analyses of the shelter effect are then conducted based on a series of simulations with different structural parameters (such as wind barrier porosity, row numbers, inter-row spacing and belt schemes). The results show that wind barriers with porosity of 0.35 could provide the longest shelter distance (i.e., where the wind velocity reduction is more than 50%) thus are recommended in engineering designs. To determine the optimal row number and belt scheme, we introduce a cost function that takes both wind-velocity reduction effects and economical expense into account. The calculated cost function show that a 3-row-belt scheme with inter-row spacing of 6h (h as the height of wind barriers) and inter-belt spacing of 12h is the most effective.

  18. Barriers and Enablers to the Implementation of School Wellness Policies: An Economic Perspective.

    Science.gov (United States)

    Schuler, Brittany R; Saksvig, Brit I; Nduka, Joy; Beckerman, Susannah; Jaspers, Lea; Black, Maureen M; Hager, Erin R

    2018-01-01

    Local wellness policies (LWPs) are mandated among school systems to enhance nutrition/physical activity opportunities in schools. Prior research notes disparities in LWP implementation. This study uses mixed methods to examine barriers/enablers to LWP implementation, comparing responses by student body income. Schools ( n = 744, 24 systems) completed an LWP implementation barriers/enablers survey. Semistructured interviews ( n = 20 random subsample) described barriers/enablers. Responses were compared by majority of lower (≥50% free/reduced-price meals; lower income [LI]) versus higher income (HI) student body. In surveys, LI and HI schools identified common barriers (parents/families, federal/state regulations, students, time, funding) and enablers (school system, teachers, food service, physical education curriculum/resources, and staff). Interviews further elucidated how staffing and funding served as enablers for all schools, and provide context for how and why barriers differed by income: time, food service (HI schools), and parents/families (LI schools). Findings support commonalities in barriers and enablers among all schools, suggesting that regardless of economic context, schools would benefit from additional supports, such as physical education and nutrition education resources integrated into existing curricula, additional funding, and personnel time dedicated to wellness programming. LI schools may benefit from additional funding to support parent and community involvement.

  19. Multilayer moisture barrier

    Science.gov (United States)

    Pankow, Joel W; Jorgensen, Gary J; Terwilliger, Kent M; Glick, Stephen H; Isomaki, Nora; Harkonen, Kari; Turkulainen, Tommy

    2015-04-21

    A moisture barrier, device or product having a moisture barrier or a method of fabricating a moisture barrier having at least a polymer layer, and interfacial layer, and a barrier layer. The polymer layer may be fabricated from any suitable polymer including, but not limited to, fluoropolymers such as polyethylene terephthalate (PET) or polyethylene naphthalate (PEN), or ethylene-tetrafluoroethylene (ETFE). The interfacial layer may be formed by atomic layer deposition (ALD). In embodiments featuring an ALD interfacial layer, the deposited interfacial substance may be, but is not limited to, Al.sub.2O.sub.3, AlSiO.sub.x, TiO.sub.2, and an Al.sub.2O.sub.3/TiO.sub.2 laminate. The barrier layer associated with the interfacial layer may be deposited by plasma enhanced chemical vapor deposition (PECVD). The barrier layer may be a SiO.sub.xN.sub.y film.

  20. An ISM approach for the barrier analysis in implementing green supply chain management

    DEFF Research Database (Denmark)

    Mathiyazhagan, K.; Govindan, Kannan; NoorulHaq, A.

    2013-01-01

    As customers are becoming more environmental conscious and governments are making stricter environmental regulations, the industries need to reduce the environmental impact of their supply chain. Indian auto component manufacturing industries especially SMEs (Small and Medium Enterprises......) are focused to cleaner production by implementing Green Supply Chain Management (GSCM) in their industries. But they are struggling to implement GSCM concept. The present research analyzes the barriers for the implementation of GSCM concept which has been divided into two phases such as identification...... dominant one for the adoption of green supply chain management and this result is helpful for industries to make easier the adoption of green concept in their supply chain by removing the dominant barrier. It indicates that different Indian auto component manufacturing industries have differing barriers...

  1. Astrocytic modulation of Blood Brain Barrier: Perspectives on Parkinson´s Disease

    Directory of Open Access Journals (Sweden)

    Ricardo eCabezas

    2014-08-01

    Full Text Available TThe blood–brain barrier (BBB is a tightly regulated interface in the Central Nervous System that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells, pericytes and astrocytes that create a neurovascular unit with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson´s Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the endothelial cells and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson´s disease and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

  2. The barrier within: endothelial transport of hormones.

    Science.gov (United States)

    Kolka, Cathryn M; Bergman, Richard N

    2012-08-01

    Hormones are involved in a plethora of processes including development and growth, metabolism, mood, and immune responses. These essential functions are dependent on the ability of the hormone to access its target tissue. In the case of endocrine hormones that are transported through the blood, this often means that the endothelium must be crossed. Many studies have shown that the concentrations of hormones and nutrients in blood can be very different from those surrounding the cells on the tissue side of the blood vessel endothelium, suggesting that transport across this barrier can be rate limiting for hormone action. This transport can be regulated by altering the surface area of the blood vessel available for diffusion through to the underlying tissue or by the permeability of the endothelium. Many hormones are known to directly or indirectly affect the endothelial barrier, thus affecting their own distribution to their target tissues. Dysfunction of the endothelial barrier is found in many diseases, particularly those associated with the metabolic syndrome. The interrelatedness of hormones may help to explain why the cluster of diseases in the metabolic syndrome occur together so frequently and suggests that treating the endothelium may ameliorate defects in more than one disease. Here, we review the structure and function of the endothelium, its contribution to the function of hormones, and its involvement in disease.

  3. Environmental Regulation and Food Safety: Studies of Protection ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2006-01-01

    Jan 1, 2006 ... Book cover Environmental Regulation and Food Safety: Studies of ... are sometimes perceived in developing countries as nontariff barriers to trade. ... In some cases, products that had initially been refused access to a ...

  4. Phenomena and characteristics of barrier river reaches in the middle and lower Yangtze River, China

    Science.gov (United States)

    You, Xingying; Tang, Jinwu

    2017-06-01

    Alluvial river self-adjustment describes the mechanism whereby a river that was originally in an equilibrium state of sediment transport encounters some disturbance that destroys the balance and results in responses such as riverbed deformation. A systematic study of historical and recent aerial photographs and topographic maps in the Middle and Lower Reaches of the Yangtze River (MLYR) shows that river self-adjustment has the distinguishing feature of transferring from upstream to downstream, which may affect flood safety, waterway morphology, bank stability, and aquatic environmental safety over relatively long reaches downstream. As a result, it is necessary to take measures to control or block this transfer. Using the relationship of the occurrence time of channel adjustments between the upstream and downstream, 34 single-thread river reaches in the MLYR were classified into four types: corresponding, basically corresponding, basically not corresponding, not corresponding. The latter two types, because of their ability to prevent upstream channel adjustment from transferring downstream, are called barrier river reaches in this study. Statistics indicate that barrier river reaches are generally single thread and slightly curved, with a narrow and deep cross-sectional morphology, and without flow deflecting nodes in the upper and middle parts of reaches. Moreover, in the MLYR, barrier river reaches have a hydrogeometric coefficient of {}1.2‱, a silty clay content of the concave bank {>}{9.5}%, and a median diameter of the bed sediment {>}{0.158} mm. The barrier river reach mechanism lies in that can effectively centralise the planimetric position of the main stream from different upstream directions, meaning that no matter how the upper channel adjusts, the main stream shows little change, providing relatively stable inflow conditions for the lower reaches. Regarding river regulation, it is necessary to optimise the benefits of barrier river reaches; long river

  5. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    Science.gov (United States)

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Implementation of hybrid pollution control techniques to regulate the ...

    African Journals Online (AJOL)

    driniev

    1999-05-13

    May 13, 1999 ... regulate the metal finishing industries in the Ethekwini. Municipality ... ment processes, process control methodology and engineering design. ..... standards. There were many barriers that had to be overcome, the most.

  7. Regulation of Endothelial Adherens Junctions by Tyrosine Phosphorylation

    Science.gov (United States)

    Adam, Alejandro Pablo

    2015-01-01

    Endothelial cells form a semipermeable, regulated barrier that limits the passage of fluid, small molecules, and leukocytes between the bloodstream and the surrounding tissues. The adherens junction, a major mechanism of intercellular adhesion, is comprised of transmembrane cadherins forming homotypic interactions between adjacent cells and associated cytoplasmic catenins linking the cadherins to the cytoskeleton. Inflammatory conditions promote the disassembly of the adherens junction and a loss of intercellular adhesion, creating openings or gaps in the endothelium through which small molecules diffuse and leukocytes transmigrate. Tyrosine kinase signaling has emerged as a central regulator of the inflammatory response, partly through direct phosphorylation and dephosphorylation of the adherens junction components. This review discusses the findings that support and those that argue against a direct effect of cadherin and catenin phosphorylation in the disassembly of the adherens junction. Recent findings indicate a complex interaction between kinases, phosphatases, and the adherens junction components that allow a fine regulation of the endothelial permeability to small molecules, leukocyte migration, and barrier resealing. PMID:26556953

  8. Thames barrier (flood protection barriers on the Thames)

    International Nuclear Information System (INIS)

    Ilkovic, J.

    2005-01-01

    In this paper the flood protection barriers on the Thames are presented. The flood protection system on the Thames in 1984 was commissioned. During two decades this barrier was used 54 times against to the high water and 34 times against storm-sewage. There is installed buttress type hydroelectric power plant

  9. Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

    Directory of Open Access Journals (Sweden)

    Lianghua Bin

    Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

  10. Review of the current state of UAV regulations

    NARCIS (Netherlands)

    Stöcker, Elvira Claudia; Bennett, Rohan; Nex, Francesco; Gerke, Markus; Zevenbergen, Jaap

    2017-01-01

    UAVs-unmanned aerial vehicles-facilitate data acquisition at temporal and spatial scales that still remain unachievable for traditional remote sensing platforms. However, current legal frameworks that regulate UAVs present significant barriers to research and development. To highlight the

  11. Two Ancient Gene Families Are Critical for Maintenance of the Mammalian Skin Barrier in Postnatal Life.

    Science.gov (United States)

    Cangkrama, Michael; Darido, Charbel; Georgy, Smitha R; Partridge, Darren; Auden, Alana; Srivastava, Seema; Wilanowski, Tomasz; Jane, Stephen M

    2016-07-01

    The skin barrier is critical for mammalian survival in the terrestrial environment, affording protection against fluid loss, microbes, toxins, and UV exposure. Many genes indispensable for barrier formation in the embryo have been identified, but loss of these genes in adult mice does not induce barrier regression. We describe a complex regulatory network centered on two ancient gene families, the grainyhead-like (Grhl) transcription factors and the protein cross-linking enzymes (tissue transglutaminases [Tgms]), which are essential for skin permeability barrier maintenance in adult mice. Embryonic deletion of Grhl3 induces loss of Tgm1 expression, which disrupts the cornified envelope, thus preventing permeability barrier formation leading to neonatal death. However, gene deletion of Grhl3 in adult mice does not disrupt the preformed barrier, with cornified envelope integrity maintained by Grhl1 and Tgm5, which are up-regulated in response to postnatal loss of Grhl3. Concomitant deletion of both Grhl factors in adult mice induced loss of Tgm1 and Tgm5 expression, perturbation of the cornified envelope, and complete permeability barrier regression that was incompatible with life. These findings define the molecular safeguards for barrier function that accompany the transition from intrauterine to terrestrial life. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Evolutionarily Conserved Roles for Blood-Brain Barrier Xenobiotic Transporters in Endogenous Steroid Partitioning and Behavior

    Directory of Open Access Journals (Sweden)

    Samantha J. Hindle

    2017-10-01

    Full Text Available Summary: Central nervous system (CNS chemical protection depends upon discrete control of small-molecule access by the blood-brain barrier (BBB. Curiously, some drugs cause CNS side-effects despite negligible transit past the BBB. To investigate this phenomenon, we asked whether the highly BBB-enriched drug efflux transporter MDR1 has dual functions in controlling drug and endogenous molecule CNS homeostasis. If this is true, then brain-impermeable drugs could induce behavioral changes by affecting brain levels of endogenous molecules. Using computational, genetic, and pharmacologic approaches across diverse organisms, we demonstrate that BBB-localized efflux transporters are critical for regulating brain levels of endogenous steroids and steroid-regulated behaviors (sleep in Drosophila and anxiety in mice. Furthermore, we show that MDR1-interacting drugs are associated with anxiety-related behaviors in humans. We propose a general mechanism for common behavioral side effects of prescription drugs: pharmacologically challenging BBB efflux transporters disrupts brain levels of endogenous substrates and implicates the BBB in behavioral regulation. : Hindle et al. shed light on the curious finding that some drugs cause behavioral side-effects despite negligible access into the brain. These authors propose a unifying hypothesis that links blood-brain barrier drug transporter function and brain access of circulating steroids to common CNS adverse drug responses. Keywords: drug side effect mechanisms, central nervous system, blood brain barrier, behavior, toxicology, drug transporters, endobiotics, steroid hormones

  13. Testing of isolation barrier sealing surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Graves, C.E.

    1994-12-15

    Isolation barrier doors are to be installed in the 105KE and 105KW basins as part of the 1994 unreviewed safety question (USQ) resolution plan to isolate the fuel storage basin from the fuel discharge chute. Included in this installation is the placement of new sealing surfaces for the barriers by affixing stainless steel plates to existing carbon steel angle bars with a specially formulated epoxy adhesive/sealant material. The sealant is a two-part component consisting of an epoxy resin (the condensation product of bisphenol A and epichlorohydrin) and a curing agent (a proprietary cycloaliphatic polyamine). The sealant is solvent free (complying with air pollution regulations) and capable of withstanding the surrounding radiation fields over an estimated 15-year service life. The epoxy sealant experiences negligible water damage partly because of its hydrophobic (water-repelling) nature. With bond tensile strengths measured at greater than 862 kPa (125 lbf/in{sup 2}), the epoxy sealant is judged acceptable for its intended application. The four-hour pot life of the epoxy sealant provides sufficient time to apply the epoxy, examine the epoxy bead for continuity, and position the stainless steel sealing plates.

  14. Testing of isolation barrier sealing surfaces

    International Nuclear Information System (INIS)

    Graves, C.E.

    1994-01-01

    Isolation barrier doors are to be installed in the 105KE and 105KW basins as part of the 1994 unreviewed safety question (USQ) resolution plan to isolate the fuel storage basin from the fuel discharge chute. Included in this installation is the placement of new sealing surfaces for the barriers by affixing stainless steel plates to existing carbon steel angle bars with a specially formulated epoxy adhesive/sealant material. The sealant is a two-part component consisting of an epoxy resin (the condensation product of bisphenol A and epichlorohydrin) and a curing agent (a proprietary cycloaliphatic polyamine). The sealant is solvent free (complying with air pollution regulations) and capable of withstanding the surrounding radiation fields over an estimated 15-year service life. The epoxy sealant experiences negligible water damage partly because of its hydrophobic (water-repelling) nature. With bond tensile strengths measured at greater than 862 kPa (125 lbf/in 2 ), the epoxy sealant is judged acceptable for its intended application. The four-hour pot life of the epoxy sealant provides sufficient time to apply the epoxy, examine the epoxy bead for continuity, and position the stainless steel sealing plates

  15. Skin barrier function

    DEFF Research Database (Denmark)

    2016-01-01

    Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

  16. Opportunities and barriers to on-farm composting and compost application: A case study from northwestern Europe.

    Science.gov (United States)

    Viaene, J; Van Lancker, J; Vandecasteele, B; Willekens, K; Bijttebier, J; Ruysschaert, G; De Neve, S; Reubens, B

    2016-02-01

    Maintaining and increasing soil quality and fertility in a sustainable way is an important challenge for modern agriculture. The burgeoning bioeconomy is likely to put further pressure on soil resources unless they are managed carefully. Compost has the potential to be an effective soil improver because of its multiple beneficial effects on soil quality. Additionally, it fits within the bioeconomy vision because it can valorize biomass from prior biomass processing or valorize biomass unsuitable for other processes. However, compost is rarely used in intensive agriculture, especially in regions with high manure surpluses. The aim of this research is to identify the barriers to on-farm composting and the application of compost in agriculture, using a mixed method approach for the case of Flanders. The significance of the 28 identified barriers is analyzed and they are categorized as market and financial, policy and institutional, scientific and technological and informational and behavioral barriers. More specifically, the shortage of woody biomass, strict regulation, considerable financial and time investment, and lack of experience and knowledge are hindering on-farm composting. The complex regulation, manure surplus, variable availability and transport of compost, and variable compost quality and composition are barriers to apply compost. In conclusion, five recommendations are suggested that could alleviate certain hindering factors and thus increase attractiveness of compost use in agriculture. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Geophysical characterization of subsurface barriers

    International Nuclear Information System (INIS)

    Borns, D.J.

    1995-08-01

    An option for controlling contaminant migration from plumes and buried waste sites is to construct a subsurface barrier of a low-permeability material. The successful application of subsurface barriers requires processes to verify the emplacement and effectiveness of barrier and to monitor the performance of a barrier after emplacement. Non destructive and remote sensing techniques, such as geophysical methods, are possible technologies to address these needs. The changes in mechanical, hydrologic and chemical properties associated with the emplacement of an engineered barrier will affect geophysical properties such a seismic velocity, electrical conductivity, and dielectric constant. Also, the barrier, once emplaced and interacting with the in situ geologic system, may affect the paths along which electrical current flows in the subsurface. These changes in properties and processes facilitate the detection and monitoring of the barrier. The approaches to characterizing and monitoring engineered barriers can be divided between (1) methods that directly image the barrier using the contrasts in physical properties between the barrier and the host soil or rock and (2) methods that reflect flow processes around or through the barrier. For example, seismic methods that delineate the changes in density and stiffness associated with the barrier represents a direct imaging method. Electrical self potential methods and flow probes based on heat flow methods represent techniques that can delineate the flow path or flow processes around and through a barrier

  18. Effective Teaching Methods in Higher Education: Requirements and Barriers.

    Science.gov (United States)

    Shirani Bidabadi, Nahid; Nasr Isfahani, Ahmmadreza; Rouhollahi, Amir; Khalili, Roya

    2016-10-01

    Teaching is one of the main components in educational planning which is a key factor in conducting educational plans. Despite the importance of good teaching, the outcomes are far from ideal. The present qualitative study aimed to investigate effective teaching in higher education in Iran based on the experiences of best professors in the country and the best local professors of Isfahan University of Technology. This qualitative content analysis study was conducted through purposeful sampling. Semi-structured interviews were conducted with ten faculty members (3 of them from the best professors in the country and 7 from the best local professors). Content analysis was performed by MAXQDA software. The codes, categories and themes were explored through an inductive process that began from semantic units or direct quotations to general themes. According to the results of this study, the best teaching approach is the mixed method (student-centered together with teacher-centered) plus educational planning and previous readiness. But whenever the teachers can teach using this method confront with some barriers and requirements; some of these requirements are prerequisite in professors' behavior and some of these are prerequisite in professors' outlook. Also, there are some major barriers, some of which are associated with the professors' operation and others are related to laws and regulations. Implications of these findings for teachers' preparation in education are discussed. In the present study, it was illustrated that a good teaching method helps the students to question their preconceptions, and motivates them to learn, by putting them in a situation in which they come to see themselves as the authors of answers, as the agents of responsibility for change. But training through this method has some barriers and requirements. To have an effective teaching; the faculty members of the universities should be awarded of these barriers and requirements as a way to

  19. Effective teaching methods in higher education: requirements and barriers

    Directory of Open Access Journals (Sweden)

    NAHID SHIRANI BIDABADI

    2016-10-01

    Full Text Available Introduction: Teaching is one of the main components in educational planning which is a key factor in conducting educational plans. Despite the importance of good teaching, the outcomes are far from ideal. The present qualitative study aimed to investigate effective teaching in higher education in Iran based on the experiences of best professors in the country and the best local professors of Isfahan University of Technology. Methods: This qualitative content analysis study was conducted through purposeful sampling. Semi-structured interviews were conducted with ten faculty members (3 of them from the best professors in the country and 7 from the best local professors. Content analysis was performed by MAXQDA software. The codes, categories and themes were explored through an inductive process that began from semantic units or direct quotations to general themes. Results: According to the results of this study, the best teaching approach is the mixed method (student-centered together with teacher-centered plus educational planning and previous readiness. But whenever the teachers can teach using this method confront with some barriers and requirements; some of these requirements are prerequisite in professors’ behavior and some of these are prerequisite in professors’ outlook. Also, there are some major barriers, some of which are associated with the professors’ operation and others are related to laws and regulations. Implications of these findings for teachers’ preparation in education are discussed. Conclusion: In the present study, it was illustrated that a good teaching method helps the students to question their preconceptions, and motivates them to learn, by putting them in a situation in which they come to see themselves as the authors of answers, as the agents of responsibility for change. But training through this method has some barriers and requirements. To have an effective teaching; the faculty members of the universities

  20. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.

    Science.gov (United States)

    Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham

    2017-12-22

    Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. Drivers and Barriers for Going Green: Perceptions from the Business Practitioners in Malaysia

    Directory of Open Access Journals (Sweden)

    S-P Loke

    2014-12-01

    found to significantly affect the company’s green initiatives. The results indicated that the main internal barriers were: it lacked of financial resources (66.2% and skilled staff (63.9%; whereas the main external barriers were: the penalty imposed were not severe enough for making any extra efforts (64.8% and the penalty was light for violation of environmental regulations (63.2%. This research had implications for the academics, practitioners and policy makers. It provided greater insights into the green practices in Malaysian firms. The research findings also urged the local governments to greatly enhance regulatory scrutiny on the production and manufacturing industries.

  2. Clinical trial regulation in Argentina: overview and analysis of regulatory framework, use of existing tools, and researchers' perspectives to identify potential barriers.

    Science.gov (United States)

    White, Lauren; Ortiz, Zulma; Cuervo, Luis G; Reveiz, Ludovic

    2011-11-01

    To review and analyze the regulatory framework of clinical trial registration, use of existing tools (publicly accessible national/international registration databases), and users' perspectives to identify possible barriers to registration compliance by sponsors and researchers in Argentina. Internationally registered trials recruiting patients in Argentina were found through clincialtrials.gov and the International Clinical Trial Registration Platform (ICTRP) and compared with publically available clinical trials registered through the National Administration of Drugs, Foods, and Medical Devices (ANMAT). A questionnaire addressing hypothesized attitudinal, knowledge-related, idiomatic, technical, economic, and regulatory barriers that could discourage or impede registration of clinical trials was developed, and semi-structured, in-depth interviews were conducted with a purposively selected sample of researchers (investigators, sponsors, and monitors) in Argentina. A response rate of 74.3% (n = 29) was achieved, and 27 interviews were ultimately used for analysis. Results suggested that the high proportion of foreign-sponsored or multinational trials (64.8% of all protocols approved by ANMAT from 1994-2006) may contribute to a communication gap between locally based investigators and foreign-based administrative officials. A lack of knowledge about available international registration tools and limited awareness of the importance of registration were also identified as limiting factors for local investigators and sponsors. To increase compliance and promote clinical trial registration in Argentina, national health authorities, sponsors, and local investigators could take the following steps: implement a grassroots educational campaign to improve clinical trial regulation, support local investigator-sponsor-initiated clinical trials, and/or encourage local and regional scientific journal compliance with standards from the International Committee of Medical Journal

  3. Information barriers

    International Nuclear Information System (INIS)

    Fuller, J.L.; Wolford, J.

    2001-01-01

    Full text: An information barrier (IB) consists of procedures and technology that prevent the release of sensitive information during a joint inspection of a sensitive nuclear item, and provides confidence that the measurement system into which it has been integrated functions exactly as designed and constructed. Work in the U.S. on radiation detection system information barriers dates back at least to 1990, even though the terminology is more recent. In January 1999 the Joint DoD-DOE Information Barrier Working Group was formed in the United States to help coordinate technical efforts related to information barrier R and D. This paper presents an overview of the efforts of this group, by its Chairs, as well as recommendations for further information barrier R and D. Progress on the demonstration of monitoring systems containing IBs is also provided. From the U.S. perspective, the basic, top-level functional requirements for the information barrier portion of an integrated radiation signature-information barrier inspection system are twofold: The host must be assured that his classified information is protected from disclosure to the inspecting party; and The inspecting party must be confident that the integrated inspection system measures, processes, and presents the radiation-signature-based measurement conclusion in an accurate and reproducible manner. It is the position of the United States that in the absence of any agreement to share classified nuclear weapons design information in the conduct of an inspection regime, the requirement to protect host country classified warhead design information is paramount and admits no tradeoff versus the confidence provided to the inspecting party in the accuracy and reproducibility of the measurements. The U.S. has reached an internal consensus on several critical design elements that define a general standard for radiation signature information barrier design. These criteria have stood the test of time under intense

  4. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  5. Tritium/hydrogen barrier development

    International Nuclear Information System (INIS)

    Hollenberg, G.W.; Simonen, E.P.; Kalinen, G.; Terlain, A.

    1994-06-01

    A review of hydrogen permeation barriers that can be applied to structural metals used in fusion power plants is presented. Both implanted and chemically available hydrogen isotopes must be controlled in fusion plants. The need for permeation barriers appears strongest in Li17-Pb blanket designs, although barriers also appear necessary for other blanket and coolant systems. Barriers that provide greater than a 1000 fold reduction in the permeation of structural metals are desired. In laboratory experiments, aluminide and titanium ceramic coatings provide permeation reduction factors, PRFS, from 1000 to over 100,000 with a wide range of scatter. The rate-controlling mechanism for hydrogen permeation through these barriers may be related to the number and type of defects in the barriers. Although these barriers appear robust and resistant to liquid metal corrosion, irradiation tests which simulate blanket environments result in very low PRFs in comparison to laboratory experiments, i.e., <150. It is anticipated from fundamental research activities that the REID enhancement of hydrogen diffusion in oxides may contribute to the lower permeation reduction factors during in-reactor experiments

  6. Barriers for realisation of energy savings in buildings; Barrierer for realisering af energibesparelser i bygninger

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, O.M.

    2004-07-01

    Many years' efforts within the energy labelling area have shown large saving potentials in heating and use of electricity in buildings. At the same time it has been proved that these saving potentials, even when economically advantageous, only are cashed to a limited extent. The reason to this is ascribed to barriers that meet the individual building owner who wants to start saving energy. Most barriers are known and a lot of these have been sought overcome for some time. The questions are how many barriers still exist, have new barriers arisen and the character of these barriers. On this background the objective of this survey has been to concretize and study the barriers, which are blocking reasonable energy savings. Focus has especially been on barriers for realisation of heating savings, but through a general evaluation of energy savings of barriers other forms of energy saving methods have been taken into consideration. Special interest has been directed towards houses, typically one family houses, which are affected by the Energy Labelling Scheme. The concept barriers include all kinds of barriers, also barriers that not are acknowledged as barriers by the individual house owner, or that on closer inspection turn out to be something else than actual barriers. This note suggests an alternative inertia model, in order to create an idea of the inertness characteristic of the many house owners who understand the message but fail to act on it. (BA)

  7. Regulation of defensive function on gingival epithelial cells can prevent periodontal disease.

    Science.gov (United States)

    Fujita, Tsuyoshi; Yoshimoto, Tetsuya; Kajiya, Mikihito; Ouhara, Kazuhisa; Matsuda, Shinji; Takemura, Tasuku; Akutagawa, Keiichi; Takeda, Katsuhiro; Mizuno, Noriyoshi; Kurihara, Hidemi

    2018-05-01

    Periodontal disease is a bacterial biofilm-associated inflammatory disease that has been implicated in many systemic diseases. A new preventive method for periodontal disease needs to be developed in order to promote the health of the elderly in a super-aged society. The gingival epithelium plays an important role as a mechanical barrier against bacterial invasion and a part of the innate immune response to infectious inflammation in periodontal tissue. The disorganization of cell-cell interactions and subsequent inflammation contribute to the initiation of periodontal disease. These make us consider that regulation of host defensive functions, epithelial barrier and neutrophil activity, may become novel preventive methods for periodontal inflammation. Based on this concept, we have found that several agents regulate the barrier function of gingival epithelial cells and suppress the accumulation of neutrophils in the gingival epithelium. We herein introduce the actions of irsogladine maleate, azithromycin, amphotericin B, and Houttuynia cordata (dokudami in Japanese), which is commonly used in traditional medicine, on the epithelial barrier and neutrophil migration in gingival epithelial cells in vivo and in vitro , in order to provide support for the clinical application of these agents to the prevention of periodontal inflammation.

  8. Systems study on engineered barriers: barrier performance analysis

    International Nuclear Information System (INIS)

    Stula, R.T.; Albert, T.E.; Kirstein, B.E.; Lester, D.H.

    1980-09-01

    A performance assessment model for multiple barrier packages containing unreprocessed spent fuel has been modified and applied to several package designs. The objective of the study was to develop information to be used in programmatic decision making concerning engineered barrier package design and development. The assessment model, BARIER, was developed in previous tasks of the System Study on Engineered Barriers (SSEB). The new version discussed in this report contains a refined and expanded corrosion rate data base which includes pitting, crack growth, and graphitization as well as bulk corrosion. Corrosion rates for oxic and anoxic conditions at each of the two temperature ranges are supplied. Other improvements include a rigorous treatment of radionuclide release after package failure which includes resistance of damaged barriers and backfill, refined temperature calculations that account for convection and radiation, a subroutine to calculate nuclear gamma radiation field at each barrier surface, refined stress calculations with reduced conservatism and various coding improvements to improve running time and core usage. This report also contains discussion of alternative scenarios to the assumed flooded repository as well as the impact of water exclusion backfills. The model was used to assess post repository closure performance for several designs which were all variation of basic designs from the Spent Unreprocessed Fuel (SURF) program. Many designs were found to delay the onset of leaching by at least a few hundreds of years in all geologic media. Long delay times for radionuclide release were found for packages with a few inches of sorption backfill. Release of uranium, plutonium, and americium was assessed

  9. Systems study on engineered barriers: barrier performance analysis

    Energy Technology Data Exchange (ETDEWEB)

    Stula, R.T.; Albert, T.E.; Kirstein, B.E.; Lester, D.H.

    1980-09-01

    A performance assessment model for multiple barrier packages containing unreprocessed spent fuel has been modified and applied to several package designs. The objective of the study was to develop information to be used in programmatic decision making concerning engineered barrier package design and development. The assessment model, BARIER, was developed in previous tasks of the System Study on Engineered Barriers (SSEB). The new version discussed in this report contains a refined and expanded corrosion rate data base which includes pitting, crack growth, and graphitization as well as bulk corrosion. Corrosion rates for oxic and anoxic conditions at each of the two temperature ranges are supplied. Other improvements include a rigorous treatment of radionuclide release after package failure which includes resistance of damaged barriers and backfill, refined temperature calculations that account for convection and radiation, a subroutine to calculate nuclear gamma radiation field at each barrier surface, refined stress calculations with reduced conservatism and various coding improvements to improve running time and core usage. This report also contains discussion of alternative scenarios to the assumed flooded repository as well as the impact of water exclusion backfills. The model was used to assess post repository closure performance for several designs which were all variation of basic designs from the Spent Unreprocessed Fuel (SURF) program. Many designs were found to delay the onset of leaching by at least a few hundreds of years in all geologic media. Long delay times for radionuclide release were found for packages with a few inches of sorption backfill. Release of uranium, plutonium, and americium was assessed.

  10. Barrier penetration database

    International Nuclear Information System (INIS)

    Fainberg, A.; Bieber, A.M. Jr.

    1978-11-01

    This document is intended to supply the NRC and nuclear power plant licensees with basic data on the times required to penetrate forcibly the types of barriers commonly found in nuclear plants. These times are necessary for design and evaluation of the physical protection system required under 10CFR73.55. Each barrier listed is described in detail. Minor variations in basic barrier construction that result in the same penetration time, are also described

  11. Design of engineered sorbent barriers

    International Nuclear Information System (INIS)

    Jones, E.O.; Freeman, H.D.

    1988-01-01

    A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper covers the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier

  12. Barrier Data Base user's guide

    International Nuclear Information System (INIS)

    Worrell, R.B.; Gould, D.J.; Wall, D.W.

    1977-06-01

    A special purpose data base for physical security barriers has been developed. In addition to barriers, the entities accommodated by the Barrier Data Base (BDB) include threats and references. A threat is established as a configuration of people and equipment which has been employed to penetrate (or attempt to penetrate) a barrier. References are used to cite publications pertinent to the barriers and threats in the data base. Utilization and maintenance of the Barrier Data Base is achieved with LIST, QUERY, ENTER, DELETE, and CHANGE commands which are used to manipulate the data base entities

  13. Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

    Directory of Open Access Journals (Sweden)

    Alexis Dumortier

    2010-02-01

    Full Text Available The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth.To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD, characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP, a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia.Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system.

  14. Design of engineered sorbent barriers

    International Nuclear Information System (INIS)

    Jones, E.O.; Freeman, H.D.

    1988-08-01

    A sorbent barrier uses sorbent material such as activated carbon or natural zeolites to prevent the migration of radionuclides from a low-level waste site to the aquifer. The sorbent barrier retards the movement of radioactive contaminants, thereby providing time for the radionuclides to decay. Sorbent barriers can be a simple, effective, and inexpensive method for reducing the migration of radionuclides to the environment. Designing a sorbent barrier consists of using soil and sorbent material properties and site conditions as input to a model which will determine the necessary sorbent barrier thickness to meet contaminant limits. The paper will cover the following areas: techniques for measuring sorption properties of barrier materials and underlying soils, use of a radionuclide transport model to determine the required barrier thickness and performance under a variety of site conditions, and cost estimates for applying the barrier. 8 refs., 6 figs., 1 tab

  15. Hanford protective barriers program: Status of asphalt barrier studies - FY 1989

    International Nuclear Information System (INIS)

    Freeman, H.D.; Gee, G.W.

    1989-11-01

    The Hanford Protective Barrier Program is evaluating alternate barriers to provide a means of meeting stringent water infiltration requirements. One type of alternate barrier being considered is an asphalt-based layer, 1.3 to 15 cm thick. Evaluations of these barriers were initiated in FY 1988, and, based on laboratory studies, two asphalt formulations were selected for further testing in small-tube lysimeters: a hot rubberized asphalt and an admixture of cationic asphalt emulsion and concrete sand containing 24 wt% residual asphalt. Eight lysimeters containing asphalt seals were installed as part of the Small Tube Lysimeter Test Facility on the Hanford Site. Two control lysimeters containing Hanford sand with a surface gravel treatment were also installed for comparison. 5 refs., 13 figs., 1 tab

  16. Barriers of Developing Medical Tourism in a Destination: A Case of South Korea.

    Science.gov (United States)

    Rokni, Ladan; Avci, Turgay; Park, Sam Hun

    2017-07-01

    This study aimed to determine the efficient factors that potentially lead to the barriers of developing medical tourism in South Korea. To explore the current medical tourism trend, a qualitative procedure was adopted. Besides analyzing the current situation of medical tourism in Korea through a systematic searching on the available information and publications, in-depth-interviews were conducted to collect data from relevant authorities and representatives of medical tourism associations in this country. The result revealed, although government have supported this industry, that lack of specialty and expertise among the health care practitioners in the scope of cross cultural communication, seems to be the core barrier to development of medical tourism in Korea. Demands for convenient promotional activities, policy making and action regulation are the other effective factors. Several strategies are required in order to address and combat these barriers, such as governmental support for cultural training, cooperative efforts to encourage health practitioners involved to enhance their cultural and linguistic competence in international scale.

  17. Barriers and solutions for expansion of electricity grids—the German experience

    International Nuclear Information System (INIS)

    Steinbach, Armin

    2013-01-01

    There is a lack of synchronization in the expansion of renewable energies and the modernization of the electricity grid infrastructure. Main barriers to grid development are the insufficient regulatory framework, an inefficient allocation of planning and authorization competences and a lack of public acceptance of new grids. As response to these barriers, Germany has implemented a fundamental reform of the planning and authorization of high voltage power lines. We analyze the new regime as to what extent it is able to eliminate existing barriers to grid expansion and thus can serve as model for other countries. We find that the establishment of a single authority competent for planning, authorization and regulation may abolish existing lack of coordination. Also, the implementation of early participation on basis of various consultations phases has been proved to be very successful in the establishment of the first grid development plan. Stricter administrative time-limits and sanctions are likely to have an accelerating effect. And an increased openness to new technologies on basis of pilot project gives grid operators more flexibility in grid development. Recently, the European Commission adopted the German approach in its policy guidelines for other EU members. - Highlights: • Assessment of barriers to electricity grid infrastructure. • Needs for better, simplified and uniform regulatory framework. • German reform of planning and authorization procedure

  18. Barriers to healthcare: Instrument development and comparison between autistic adults and adults with and without other disabilities.

    Science.gov (United States)

    Raymaker, Dora M; McDonald, Katherine E; Ashkenazy, Elesia; Gerrity, Martha; Baggs, Amelia M; Kripke, Clarissa; Hourston, Sarah; Nicolaidis, Christina

    2017-11-01

    Our objective was to use a community-based participatory research approach to identify and compare barriers to healthcare experienced by autistic adults and adults with and without other disabilities. To do so, we developed a Long- and Short-Form instrument to assess barriers in clinical and research settings. Using the Barriers to Healthcare Checklist-Long Form, we surveyed 437 participants (209 autistic, 55 non-autistic with disabilities, and 173 non-autistic without disabilities). Autistic participants selected different and greater barriers to healthcare, particularly in areas related to emotional regulation, patient-provider communication, sensory sensitivity, and healthcare navigation. Top barriers were fear or anxiety (35% (n = 74)), not being able to process information fast enough to participate in real-time discussions about healthcare (32% (n = 67)), concern about cost (30% (n = 62)), facilities causing sensory issues 30% ((n = 62)), and difficulty communicating with providers (29% (n = 61)). The Long Form instrument exhibited good content and construct validity. The items combined to create the Short Form had predominantly high levels of correlation (range 0.2-0.8, p barriers, and urge more intervention research to explore means for removing them.

  19. Embryonic Blood-Cerebrospinal Fluid Barrier Formation and Function

    Directory of Open Access Journals (Sweden)

    David eBueno

    2014-10-01

    Full Text Available During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF. CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS. The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF.

  20. Barrier cell sheath formation

    International Nuclear Information System (INIS)

    Kesner, J.

    1980-04-01

    The solution for electrostatic potential within a simply modeled tandem mirror thermal barrier is seen to exhibit a sheath at each edge of the cell. The formation of the sheath requires ion collisionality and the analysis assmes that the collisional trapping rate into the barrier is considerably slower than the barrier pump rate

  1. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation

    Directory of Open Access Journals (Sweden)

    Luissint Anny-Claude

    2012-11-01

    Full Text Available Abstract The Blood–brain barrier (BBB, present at the level of the endothelium of cerebral blood vessels, selectively restricts the blood-to-brain paracellular diffusion of compounds; it is mandatory for cerebral homeostasis and proper neuronal function. The barrier properties of these specialized endothelial cells notably depend on tight junctions (TJs between adjacent cells: TJs are dynamic structures consisting of a number of transmembrane and membrane-associated cytoplasmic proteins, which are assembled in a multimolecular complex and acting as a platform for intracellular signaling. Although the structural composition of these complexes has been well described in the recent years, our knowledge about their functional regulation still remains fragmentary. Importantly, pericytes, embedded in the vascular basement membrane, and perivascular microglial cells, astrocytes and neurons contribute to the regulation of endothelial TJs and BBB function, altogether constituting the so-called neurovascular unit. The present review summarizes our current understanding of the structure and functional regulation of endothelial TJs at the BBB. Accumulating evidence points to a correlation between BBB dysfunction, alteration of TJ complexes and progression of a variety of CNS diseases, such as stroke, multiple sclerosis and brain tumors, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s diseases. Understanding how TJ integrity is controlled may thus help improve drug delivery across the BBB and the design of therapeutic strategies for neurological disorders.

  2. Biosensor Technology Reveals the Disruption of the Endothelial Barrier Function and the Subsequent Death of Blood Brain Barrier Endothelial Cells to Sodium Azide and Its Gaseous Products.

    Science.gov (United States)

    Kho, Dan T; Johnson, Rebecca H; O'Carroll, Simon J; Angel, Catherine E; Graham, E Scott

    2017-09-21

    Herein we demonstrate the sensitive nature of human blood-brain barrier (BBB) endothelial cells to sodium azide and its gaseous product. Sodium azide is known to be acutely cytotoxic at low millimolar concentrations, hence its use as a biological preservative (e.g., in antibodies). Loss of barrier integrity was noticed in experiments using Electric Cell-substrate Impedance Sensing (ECIS) biosensor technology, to measure endothelial barrier integrity continuously in real-time. Initially the effect of sodium azide was observed as an artefact where it was present in antibodies being employed in neutralisation experiments. This was confirmed where antibody clones that were azide-free did not mediate loss of barrier function. A delayed loss of barrier function in neighbouring wells implied the influence of a liberated gaseous product. ECIS technology demonstrated that the BBB endothelial cells had a lower level of direct sensitivity to sodium azide of ~3 µM. Evidence of gaseous toxicity was consistently observed at 30 µM and above, with disrupted barrier function and cell death in neighbouring wells. We highlight the ability of this cellular biosensor technology to reveal both the direct and gaseous toxicity mediated by sodium azide. The sensitivity and temporal dimension of ECIS technology was instrumental in these observations. These findings have substantial implications for the wide use of sodium azide in biological reagents, raising issues of their application in live-cell assays and with regard to the protection of the user. This research also has wider relevance highlighting the sensitivity of brain endothelial cells to a known mitochondrial disruptor. It is logical to hypothesise that BBB endothelial dysfunction due to mitochondrial dys-regulation could have an important but underappreciated role in a range of neurological diseases.

  3. Barriers to the future

    Energy Technology Data Exchange (ETDEWEB)

    Massey, C T

    1986-09-01

    Opportunities for the British coal industry seem vast yet there are still barriers to progress. Seven areas are identified and discussed: mining mobility (for example, longwall mining systems are rigid and inflexible compared with American stall and pillar working); mine structure (many mines are more suitable to pit ponies than to large pieces of equipment); financial barriers (Government requires the industry to break even in 1987/88); personnel barriers (less specialization, better use of skills); safety barriers (increased use of remote control, ergonomics and robotics to protect workers); microelectronic management (nationalization has cushioned management from the market place; there is a need for a more multidisciplinary approach to the industry); and legal barriers (most legislation in the past has been in response to accidents; legislation external to the industry but affecting it is more fundamental).

  4. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury

    Directory of Open Access Journals (Sweden)

    Huiying Liu

    2016-12-01

    Full Text Available Background Acute lung injury and acute respiratory distress syndrome (ALI/ARDS is a severe clinical syndrome with mortality rate as high as 30–40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs exhibit make it possible to regulate the homeostatic control of S1P. Methods By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. Results It was found that the down-regulation of TNF-α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. Discussions The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1

  5. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury.

    Science.gov (United States)

    Liu, Huiying; Zhang, Zili; Li, Puyuan; Yuan, Xin; Zheng, Jing; Liu, Jinwen; Bai, Changqing; Niu, Wenkai

    2016-01-01

    Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30-40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P. By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. It was found that the down-regulation of TNF- α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their possible synergistic mechanism.

  6. Modeling and Simulation of Long-Term Performance of Near-Surface Barriers

    International Nuclear Information System (INIS)

    Piet, S. J.; Jacobson, J. J.; Martian, P.; Martineau, R.; Soto, R.

    2003-01-01

    Society has and will continue to generate hazardous wastes whose risks must be managed. For exceptionally toxic, long-lived, and feared waste, the solution is deep burial, e.g., deep geological disposal at Yucca Mtn. For some waste, recycle or destruction/treatment is possible. The alternative for other wastes is storage at or near the ground level (in someone's back yard); most of these storage sites include a surface barrier (cap) to prevent migration of the waste due to infiltration of surface water. The design lifespan for such barriers ranges from 30 to 1000 years, depending on hazard and regulations. In light of historical performance, society needs a better basis for predicting barrier performance over long time periods and tools for optimizing maintenance of barriers while in service. We believe that, as in other industries, better understanding of the dynamics of barrier system degradation will enable improved barriers (cheaper, longer-lived, simpler, easier to maintain) and improved maintenance. We are focusing our research on earthen caps, especially those with evapo-transpiration and capillary breaks. Typical cap assessments treat the barrier's structure as static prior to some defined lifetime. Environmental boundary conditions such as precipitation and temperature are treated as time dependent. However, other key elements of the barrier system are regarded as constant, including engineered inputs (e.g., fire management strategy, irrigation, vegetation control), surface ecology (critical to assessment of plant transpiration), capillary break interface, material properties, surface erosion rate, etc. Further, to be conservative, only harmful processes are typically considered. A more holistic examination of both harmful and beneficial processes will provide more realistic pre-service prediction and in-service assessment of performance as well as provide designers a tool to encourage beneficial processes while discouraging harmful processes. Thus, the

  7. Chemical barriers for controlling groundwater contamination

    International Nuclear Information System (INIS)

    Morrison, S.J.; Spangler, R.R.

    1993-01-01

    Chemical barriers are being explored as a low-cost means of controlling groundwater contamination. The barrier can intercept a contaminant plume and prevent migration by transferring contaminants from the groundwater to immobile solids. A chemical barrier can be emplaced in a landfill liner or in an aquifer cutoff wall or can be injected into a contaminant plume. Chemical barriers can be classified as either precipitation barriers or sorption barriers depending upon the dominant mode of contaminant extraction. In a precipitation barrier, contaminants are bound in the structures of newly formed phases; whereas, in a sorption barrier, contaminants attach to the surfaces of preexisting solids by adsorption or some other surface mechanism. Sorption of contaminants is pH dependent. A precipitation barrier can control the pH of the system, but alkaline groundwater may dominate the pH in a sorption barrier. A comparison is made of the characteristics of precipitation and sorption barriers. Experimental data on the extraction of uranium and molybdenum from simulated groundwater are used to demonstrate these concepts. 10 refs., 9 figs., 1 tab

  8. Barrier mechanisms in the Drosophila blood-brain barrier.

    Science.gov (United States)

    Hindle, Samantha J; Bainton, Roland J

    2014-01-01

    The invertebrate blood-brain barrier (BBB) field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through G-protein coupled receptor signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate BBB has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many BBB mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the BBB can govern whole animal physiologies. This includes novel functions of BBB gap junctions in orchestrating synchronized neuroblast proliferation, and of BBB secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate BBB anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  9. Barriers against psychosocial communication: oncologists' perceptions.

    Science.gov (United States)

    Fagerlind, Hanna; Kettis, Åsa; Glimelius, Bengt; Ring, Lena

    2013-10-20

    To explore oncologists' psychosocial attitudes and beliefs and their perceptions regarding barriers against psychosocial communication. A questionnaire was distributed to oncologists in Sweden (n = 537). Questions covered demography, the Physician Psychosocial Beliefs Scale (PPBS), and barriers against psychosocial communication. Stepwise multiple regression was used to determine what factors contribute the most to the PPBS score and the total number of barriers and barriers affecting clinical practice, respectively. Spearman rank-order correlation was used to determine correlation between PPBS score and number of barriers. Questionnaire response rate was 64%. Mean PPBS value was 85.5 (range, 49 to 123; SD, 13.0). Most oncologists (93%) perceived one or more barriers in communicating psychosocial aspects with patients. On average, five different communication barriers were perceived, of which most were perceived to affect clinical practice. These barriers included insufficient consultation time, lack of resources for taking care of problems discovered, and lack of methods to evaluate patients' psychosocial health in clinical practice. There was a positive correlation (rs = 0.490; P barriers (ie, less psychosocially oriented oncologists perceived more barriers). Oncologists with supplementary education with a psychosocial focus perceived fewer barriers/barriers affecting clinical practice (P barriers affecting psychosocial communication in clinical practice. Interventions aiming to improve psychosocial communication must therefore be multifaceted and individualized to clinics and individual oncologists. It is important to minimize barriers to facilitate optimal care and treatment of patients with cancer.

  10. Barriers to improvements in energy efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the barriers'' literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  11. Barriers to improvements in energy efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, A.K.N.

    1991-10-01

    To promote energy-efficiency improvements, actions may be required at one or more levels -- from the lowest level of the consumer (residential, commercial, industrial, etc.) through the highest level of the global agencies. But barriers to the implementation of energy-efficiency improvements exist or can arise at all these levels. Taking up each one of these barriers in turn, the paper discusses specific measures that can contribute to overcoming the barriers. However, a one-barrier-one-measure approach must be avoided. Single barriers may in fact involve several sub-barriers. Also, combinations of measures are much more effective in overcoming barriers. In particular, combinations of measures that simultaneously overcome several barriers are most successful. The paper discusses the typology of barriers, explores their origin and suggests measures that by themselves or in combination with other measures, will overcome these barriers. Since most of the barriers dealt with can be found in the ``barriers`` literature, any originality in the paper lies in its systematic organization, synoptic view and holistic treatment of this issue. This paper is intended to initiate a comprehensive treatment of barriers, their origins and the measures that contribute to overcoming them. Hopefully, such a treatment will facilitate the implementation of energy-efficiency improvements involving a wide diversity of ever-changing energy end uses and consumer preferences.

  12. Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier.

    Science.gov (United States)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim

    2016-11-01

    The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.

  13. The blood-tendon barrier: identification and characterisation of a novel tissue barrier in tendon blood vessels

    Directory of Open Access Journals (Sweden)

    C Lehner

    2016-05-01

    Full Text Available Tissue barriers function as “gate keepers” between different compartments (usually blood and tissue and are formed by specialised membrane-associated proteins, localising to the apicolateral plasma membrane domain of epithelial and endothelial cells. By sealing the paracellular space, the free diffusion of solutes and molecules across epithelia and endothelia is impeded. Thereby, tissue barriers contribute to the establishment and maintenance of a distinct internal and external environment, which is crucial during organ development and allows maintenance of an organ-specific homeostatic milieu. So far, various epithelial and endothelial tissue barriers have been described, including the blood-brain barrier, the blood-retina barrier, the blood-testis barrier, the blood-placenta barrier, and the cerebrospinal fluid (CSF-brain barrier, which are vital for physiological function and any disturbance of these barriers can result in severe organ damage or even death. Here, we describe the identification of a novel barrier, located in the vascular bed of tendons, which we term the blood-tendon barrier (BTB. By using immunohistochemistry, transmission electron microscopy, and tracer studies we demonstrate the presence of a functional endothelial barrier within tendons restricting the passage of large blood-borne molecules into the surrounding tendon tissue. We further provide in vitro evidence that the BTB potentially contributes to the creation of a distinct internal tissue environment impacting upon the proliferation and differentiation of tendon-resident cells, effects which might be fundamental for the onset of tendon pathologies.

  14. Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

    Science.gov (United States)

    Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

    2017-12-01

    Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Rudolf eLucas

    2013-08-01

    Full Text Available The integrity of epithelial and endothelial barriers in the lower airspaces of the lungs has to be tightly regulated, in order to prevent leakage and to assure efficient gas exchange between the alveoli and capillaries. Both G- and G+ bacterial toxins, such as LPS and pneumolysin, respectively, can be released in high concentrations within the pulmonary compartments upon antibiotic treatment of patients suffering from acute respiratory distress syndrome (ARDS or severe pneumonia. These toxins are able to impair endothelial barrier function, either directly, or indirectly, by induction of pro-inflammatory mediators and neutrophil sequestration. Toxin-induced endothelial hyperpermeability can involve myosin light chain phosphorylation and/or microtubule rearrangement. Endothelial nitric oxide synthase (eNOS was proposed to be a guardian of basal barrier function, since eNOS knock-out mice display an impaired expression of inter-endothelial junction proteins and as such an increased vascular permeability, as compared to wild type mice. The enzyme arginase, the activity of which can be regulated by the redox status of the cell, exists in two isoforms - arginase 1 (cytosolic and arginase 2 (mitochondrial - both of which can be expressed in lung microvascular endothelial cells. Upon activation, arginase competes with eNOS for the substrate L-arginine, as such impairing eNOS-dependent NO generation and promoting ROS generation by the enzyme. This mini-review will discuss recent findings regarding the interaction between bacterial toxins and arginase during acute lung injury and will as such address the role of arginase in bacterial toxin-induced pulmonary endothelial barrier dysfunction.

  16. Effect of the barrier properties on the surface part of the barrier discharge

    International Nuclear Information System (INIS)

    Sokolova, M.V.; Zhukov, S.V.

    1998-01-01

    The effect of barrier characteristics on the discharge processes in a barrier discharge was investigated, main attention being paid to the amount and distribution of the charge left on the barrier surface by the volume discharge in the main air gap. The measurements show that the main part of the gap charge is due to the volume part of the discharge. The measured values of the surface charge significantly increase with the voltage applied and with the length of the gas gap, while the dimensions of the charge spot and the distribution of charge density are determined by the barrier properties. (J.U.)

  17. Perceived barriers to communication between hospital and nursing home at time of patient transfer.

    Science.gov (United States)

    Shah, Faraaz; Burack, Orah; Boockvar, Kenneth S

    2010-05-01

    To identify perceived barriers to communication between hospital and nursing home at the time of patient transfer and examine associations between perceived barriers and hospital and nursing home characteristics. Mailed survey. Medicare- or Medicaid-certified nursing homes in New York State. Nursing home administrators, with input from other nursing home staff. Respondents rated the importance as a barrier to hospital-nursing home communication of (1) hospital providers' attitude, time, effort, training, payment, and familiarity with nursing home patients; (2) unplanned and off-hours transfers; (3) HIPAA privacy regulations; and (4) lost or failed information transmission. Associations were determined between barriers and the following organizational characteristics: (1) hospital-nursing home affiliations, pharmacy or laboratory agreements, cross-site staff visits, and cross-site physician care; (2) hospital size, teaching status, and frequency of geriatrics specialty care; (3) nursing home size, location, type, staffing, and Medicare quality indicators; and (4) hospital-to-nursing home communication, consistency of hospital care with health care goals, and communication quality improvement efforts. Of 647 questionnaires sent, 229 were returned (35.4%). The most frequently reported perceived barriers to communication were sudden or unplanned transfers (44.4%), transfers that occur at night or on the weekend (41.4%), and hospital providers' lack of effort (51.0%), lack of familiarity with patients (45.0%), and lack of time (43.5%). Increased hospital size, teaching hospitals, and urban nursing home location were associated with greater perceived importance of these barriers, and cross-site staff visits and hospital provision of laboratory and pharmacy services to the nursing home were associated with lower perceived importance of these barriers. Hospital and nursing home characteristics and interorganizational relationships were associated with nursing home

  18. Transport barriers in plasmas

    International Nuclear Information System (INIS)

    Caldas, I L; Szezech, J D Jr; Kroetz, T; Marcus, F A; Roberto, M; Viana, R L; Lopes, S R

    2012-01-01

    We discuss the creation of transport barriers in magnetically confined plasmas with non monotonic equilibrium radial profiles. These barriers reduce the transport in the shearless region (i.e., where the twist condition does not hold). For the chaotic motion of particles in an equilibrium electric field with a nonmonotonic radial profile, perturbed by electrostatic waves, we show that a nontwist transport barrier can be created in the plasma by modifying the electric field radial profile. We also show non twist barriers in chaotic magnetic field line transport in the plasma near to the tokamak wall with resonant modes due to electric currents in external coils.

  19. Barriers and drivers for energy efficiency: Different perspectives from an exploratory study in the Netherlands

    International Nuclear Information System (INIS)

    Cagno, Enrico; Trianni, Andrea; Abeelen, Christiaan; Worrell, Ernst; Miggiano, Federica

    2015-01-01

    Highlights: • We investigated the perception of barriers and drivers and mechanisms regulating them. • Firms agree on the most important barriers and drivers. • Firms agree on the most critical decision-making steps and actors promoting drivers. • Major external actors perceive barriers, drivers and mechanisms differently. • Success of voluntary agreements depends on the link to other policy instruments. - Abstract: Increased energy efficiency represents a crucial opportunity for European industrial sustainability, but several barriers still need to be tackled. Thus, it is crucial to understand the existing mismatches between the perception of enterprises and what the major actors promoting energy efficiency believe enterprises suffer from and need within the decision-making process. To do so, we have performed an exploratory investigation analysing a set of manufacturing enterprises participating in the Dutch voluntary agreements. The study involved the major external actors, i.e. the national energy agency, governmental and industrial organisations, to map their views on the decision-making process. Results show that enterprises agree not only on the most important barriers and drivers, but also on the mechanisms underlying them. However, even a general common understanding of the barriers is disputed when major external actors are considered, as they only agree on the primary role of economic barriers. Mismatches appear when considering how single barriers affect the decision-making process and which drivers – and actors promoting them – need to be addressed. Although voluntary agreements represent the most popular instrument on energy efficiency in the Netherlands, they do not seem to be considered by small and medium-sized enterprises as a stimulus for improving energy efficiency. Crucial for future success are the link with other policy instruments, and the degree to which the instruments trigger the right drivers and barriers at the right

  20. The Mechanisms and Quantification of the Selective Permeability in Transport Across Biological Barriers : the Example of Kyotorphin

    NARCIS (Netherlands)

    Serrano, Isa D.; Freire, Joao M.; Carvalho, Miguel V.; Neves, Mafalda; Melo, Manuel N.; Castanho, Miguel A. R. B.

    2014-01-01

    This paper addresses the mechanisms behind selective endothelial permeability and their regulations. The singular properties of each of the seven blood-tissues barriers. Then, it further revisits the physical, quantitative meaning of permeability, and the way it should be measured based on sound

  1. Devices for overcoming biological barriers: the use of physical forces to disrupt the barriers.

    Science.gov (United States)

    Mitragotri, Samir

    2013-01-01

    Overcoming biological barriers including skin, mucosal membranes, blood brain barrier as well as cell and nuclear membrane constitutes a key hurdle in the field of drug delivery. While these barriers serve the natural protective function in the body, they limit delivery of drugs into the body. A variety of methods have been developed to overcome these barriers including formulations, targeting peptides and device-based technologies. This review focuses on the use of physical methods including acoustic devices, electric devices, high-pressure devices, microneedles and optical devices for disrupting various barriers in the body including skin and other membranes. A summary of the working principles of these devices and their ability to enhance drug delivery is presented. Copyright © 2012. Published by Elsevier B.V.

  2. Cosmetic Regulations: A Comparative Study.

    Science.gov (United States)

    Suhag, Jyoti; Dureja, Harish

    2015-01-01

    The regulatory framework, compliance requirement, efficacy, safety, and marketing of cosmetic products are considered the most important factors for growth of the cosmetic industry. There are different regulatory bodies across the globe that have their own insights for regulation; moreover, governments such as the United States, European Union, and Japan follow a stringent regulatory framework, whereas cosmetics are not so much strictly regulated in countries such as India, Brazil, and China. The alignment of a regulatory framework will play a significant role in the removal of barriers to trade, growth of market at an international level, innovation in the development and presentation of new products, and most importantly safety and efficacy of the marketed products. The present contribution gives insight into the important cosmetic regulations in areas of premarket approval, ingredient control, and labeling and warnings, with a special focus on the cosmetic regulatory environments in the United States, European Union, Japan, and India. Most importantly, the authors highlight the dark side of cosmetics associated with allergic reactions and even skin cancer. The importance of cosmetic regulations has been highlighted by dint of which the society can be healthier, accomplished by more stringent and harmonized regulations.

  3. Falling short: how state laws can address health information exchange barriers and enablers.

    Science.gov (United States)

    Schmit, Cason D; Wetter, Sarah A; Kash, Bita A

    2018-06-01

    Research on the implementation of health information exchange (HIE) organizations has identified both positive and negative effects of laws relating to governance, incentives, mandates, sustainability, stakeholder participation, patient engagement, privacy, confidentiality, and security. We fill a substantial research gap by describing whether comprehensive state and territorial HIE legal frameworks address identified legal facilitators and barriers. We used the Westlaw database to identify state and territorial laws relating to HIEs in effect on June 7, 2016 (53 jurisdictions). We blind-coded all laws and addressed coding discrepancies in peer-review meetings. We recorded a consensus code for each law in a master database. We compared 20 HIE legal attributes with identified barriers to and enablers of HIE activity in the literature. Forty-two states, the District of Columbia, and 2 territories have laws relating to HIEs. On average, jurisdictions address 8.32 of the 20 criteria selected in statutes and regulations. Twenty jurisdictions unambiguously address ≤5 criteria in statutes and regulations. None of the significant legal criteria are unambiguously addressed in >60% of the 53 jurisdictions. Laws can be barriers to or enablers of HIEs. However, jurisdictions are not addressing many significant issues identified by researchers. Consequently, there is a substantial risk that existing legal frameworks are not adequately supporting HIEs. The current evidence base is insufficient for comparative assessments or impact rankings of the various factors. However, the detailed Centers for Disease Control and Prevention dataset of HIE laws could enable investigations into the types of laws that promote or impede HIEs.

  4. Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function.

    Science.gov (United States)

    Sayedyahossein, Samar; Rudkouskaya, Alena; Leclerc, Valerie; Dagnino, Lina

    2016-02-01

    A functional permeability barrier is essential to prevent the passage of water and electrolytes, macromolecules, and pathogens through the epidermis. This is accomplished in terminally differentiated keratinocytes through formation of a cornified envelope and the assembly of tight intercellular junctions. Integrin-linked kinase (ILK) is a scaffold protein essential for hair follicle morphogenesis and epidermal attachment to the basement membrane. However, the biological functions of ILK in differentiated keratinocytes remain poorly understood. Furthermore, whether ILK is implicated in keratinocyte differentiation and intercellular junction formation has remained an unresolved issue. Here we describe a pivotal role for ILK in keratinocyte differentiation responses to increased extracellular Ca(2+), regulation of adherens and tight junction assembly, and the formation of an outside-in permeability barrier toward macromolecules. In the absence of ILK, the calcium sensing receptor, E-cadherin, and ZO-1 fail to translocate to the cell membrane, through mechanisms that involve abnormalities in microtubules and in RhoA activation. In situ, ILK-deficient epidermis exhibits reduced tight junction formation and increased outside-in permeability to a dextran tracer, indicating reduced barrier properties toward macromolecules. Therefore, ILK is an essential component of keratinocyte differentiation programs that contribute to epidermal integrity and the establishment of its barrier properties. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Non-Saccharomyces yeasts protect against epithelial cell barrier disruption induced by Salmonella enterica subsp. enterica serovar Typhimurium.

    Science.gov (United States)

    Smith, I M; Baker, A; Arneborg, N; Jespersen, L

    2015-11-01

    The human gastrointestinal epithelium makes up the largest barrier separating the body from the external environment. Whereas invasive pathogens cause epithelial barrier disruption, probiotic micro-organisms modulate tight junction regulation and improve epithelial barrier function. In addition, probiotic strains may be able to reduce epithelial barrier disruption caused by pathogenic species. The aim of this study was to explore non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Benchmarking against established probiotic strains, we evaluated the ability of four nonpathogenic yeast species to modulate transepithelial electrical resistance (TER) across a monolayer of differentiated human colonocytes (Caco-2 cells). Further, we assessed yeast modulation of a Salmonella Typhimurium-induced epithelial cell barrier function insult. Our findings demonstrate distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function. While the established probiotic yeast Saccharomyces boulardii increased TER across a Caco-2 monolayer by 30%, Kluyveromyces marxianus exhibited significantly stronger properties of TER enhancement (50% TER increase). In addition, our data demonstrate significant yeast-mediated modulation of Salmonella-induced epithelial cell barrier disruption and identify K. marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study demonstrates distinct patterns of non-Saccharomyces yeast modulation of epithelial cell barrier function in vitro. Further, our data demonstrate significant yeast-mediated modulation of Salmonella Typhimurium-induced epithelial cell barrier disruption and identify Kluyveromyces marxianus and Metschnikowia gruessii as two non-Saccharomyces yeasts capable of protecting human epithelial cells from pathogen invasion. This study is the first to demonstrate significant non-Saccharomyces yeast

  6. Performing a local barrier operation

    Science.gov (United States)

    Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

    2014-03-04

    Performing a local barrier operation with parallel tasks executing on a compute node including, for each task: retrieving a present value of a counter; calculating, in dependence upon the present value of the counter and a total number of tasks performing the local barrier operation, a base value, the base value representing the counter's value prior to any task joining the local barrier; calculating, in dependence upon the base value and the total number of tasks performing the local barrier operation, a target value of the counter, the target value representing the counter's value when all tasks have joined the local barrier; joining the local barrier, including atomically incrementing the value of the counter; and repetitively, until the present value of the counter is no less than the target value of the counter: retrieving the present value of the counter and determining whether the present value equals the target value.

  7. How hormones influence composition and physiological function of the brain-blood barrier.

    Science.gov (United States)

    Hampl, R; Bičíková, M; Sosvorová, L

    2015-01-01

    Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves.

  8. Barriers of Developing Medical Tourism in a Destination: A Case of South Korea

    Science.gov (United States)

    ROKNI, Ladan; AVCI, Turgay; PARK, Sam Hun

    2017-01-01

    Background: This study aimed to determine the efficient factors that potentially lead to the barriers of developing medical tourism in South Korea. Methods: To explore the current medical tourism trend, a qualitative procedure was adopted. Besides analyzing the current situation of medical tourism in Korea through a systematic searching on the available information and publications, in-depth-interviews were conducted to collect data from relevant authorities and representatives of medical tourism associations in this country. Results: The result revealed, although government have supported this industry, that lack of specialty and expertise among the health care practitioners in the scope of cross cultural communication, seems to be the core barrier to development of medical tourism in Korea. Demands for convenient promotional activities, policy making and action regulation are the other effective factors. Discussion: Several strategies are required in order to address and combat these barriers, such as governmental support for cultural training, cooperative efforts to encourage health practitioners involved to enhance their cultural and linguistic competence in international scale. PMID:28845404

  9. Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier dysfunction in acute lung injury.

    Science.gov (United States)

    Slavin, Spencer A; Leonard, Antony; Grose, Valerie; Fazal, Fabeha; Rahman, Arshad

    2018-03-01

    Autophagy is an evolutionarily conserved cellular process that facilitates the continuous recycling of intracellular components (organelles and proteins) and provides an alternative source of energy when nutrients are scarce. Recent studies have implicated autophagy in many disorders, including pulmonary diseases. However, the role of autophagy in endothelial cell (EC) barrier dysfunction and its relevance in the context of acute lung injury (ALI) remain uncertain. Here, we provide evidence that autophagy is a critical component of EC barrier disruption in ALI. Using an aerosolized bacterial lipopolysaccharide (LPS) inhalation mouse model of ALI, we found that administration of the autophagy inhibitor 3-methyladenine (3-MA), either prophylactically or therapeutically, markedly reduced lung vascular leakage and tissue edema. 3-MA was also effective in reducing the levels of proinflammatory mediators and lung neutrophil sequestration induced by LPS. To test the possibility that autophagy in EC could contribute to lung vascular injury, we addressed its role in the mechanism of EC barrier disruption. Knockdown of ATG5, an essential regulator of autophagy, attenuated thrombin-induced EC barrier disruption, confirming the involvement of autophagy in the response. Similarly, exposure of cells to 3-MA, either before or after thrombin, protected against EC barrier dysfunction by inhibiting the cleavage and loss of vascular endothelial cadherin at adherens junctions, as well as formation of actin stress fibers. 3-MA also reversed LPS-induced EC barrier disruption. Together, these data imply a role of autophagy in lung vascular injury and reveal the protective and therapeutic utility of 3-MA against ALI.

  10. Barrier island facies models and recognition criteria

    Science.gov (United States)

    Mulhern, J.; Johnson, C. L.

    2017-12-01

    Barrier island outcrops record transgressive shoreline motion at geologic timescales, providing integral clues to understanding how coastlines respond to rising sea levels. However, barrier island deposits are difficult to recognize. While significant progress has been made in understanding the modern coastal morphodynamics, this insight is not fully leveraged in existing barrier island facies models. Excellent outcrop exposures of the paralic Upper Cretaceous Straight Cliffs Formation of southern Utah provide an opportunity to revise facies models and recognition criteria for barrier island deposits. Preserved barrier islands are composed of three main architectural elements (shorefaces, tidal inlets, and tidal channels) which occur independently or in combination to create larger-scale barrier island deposits. Barrier island shorefaces record progradation, while barrier island tidal inlets record lateral migration, and barrier island tidal channels record aggradation within the tidal inlet. Four facies associations are used to describe and characterize these barrier island architectural elements. Barrier islands occur in association with backarrier fill and internally contain lower and upper shoreface, high-energy upper shoreface, and tidal channel facies. Barrier islands bound lagoons or estuaries, and are distinguished from other shoreface deposits by their internal facies and geometry, association with backbarrier facies, and position within transgressive successions. Tidal processes, in particular tidal inlet migration and reworking of the upper shoreface, also distinguish barrier island deposits. Existing barrier island models highlight the short term heterogeneous and dynamic nature of barrier island systems, yet overlook processes tied to geologic time scales, such as multi-directional motion, erosion, and reworking, and their expressions in preserved barrier island strata. This study uses characteristic outcrop expressions of barrier island successions to

  11. Enershield : energy saving air barriers

    Energy Technology Data Exchange (ETDEWEB)

    Hallihan, D. [Enershield Industries Ltd., Edmonton, AB (Canada)

    2008-07-01

    Enershield Industries is a leader in air barrier technology and provides solution for the Canadian climate. This presentation described the advantages of air barriers and the impact of rising energy costs. An air barrier is used to separate areas of differing environments and makes existing building systems more efficient. This presentation discussed how an air barrier works. It also identified how Enershield Industries calculates energy savings. It described air barrier applications and those who use barrier technology. These include the commercial and industrial sector as well as the personnel and retail sector. Barrier technology can be used for cold storage; vehicle and equipment washes; food processing; and environmental separation. Features and benefits such as the ability to create seal, acoustic insulation, and long term durability were also discussed. Last, the presentation addressed model selection and design criteria issues. Design criteria that were presented included a discussion of acoustic installation, articulating nozzles, scroll cased fans, and structural frame. Other design criteria presented were galvanized frames, telescopic sliders, and off the shelf parts. It was concluded that the ability to reduce energy consumption and enhance employee/client comfort is beneficial to the employer as well as to the employee. figs.

  12. Engineered barriers: current status

    International Nuclear Information System (INIS)

    Atkinson, A.; Marsh, G.P.

    1988-01-01

    This report summarises the current state of research relevant to assessing the performance of engineered barriers made of steel and concrete in radioactive waste repositories. The objective of these barriers is to contain the radionuclides within them by providing both physical and chemical impediment to their release. The physical barriers are of most value for highly soluble isotopes with relatively short half-lives (eg 137 Cs), since they can provide containment until a large fraction of the activity has decayed. In addition they can facilitate retrievability for some period after disposal. The chemical barriers operate by beneficial conditioning of the near field groundwater and providing sites for sorption of radionuclides. Both of these reduce the aqueous concentration of radionuclides in the near field. (author)

  13. ROBO4-Mediated Vascular Integrity Regulates the Directionality of Hematopoietic Stem Cell Trafficking

    Directory of Open Access Journals (Sweden)

    Stephanie Smith-Berdan

    2015-02-01

    Full Text Available Despite the use of hematopoietic stem cells (HSCs in clinical therapy for over half a century, the mechanisms that regulate HSC trafficking, engraftment, and life-long persistence after transplantation are unclear. Here, we show that the vascular endothelium regulates HSC trafficking into and out of bone marrow (BM niches. Surprisingly, we found that instead of acting as barriers to cellular entry, vascular endothelial cells, via the guidance molecule ROBO4, actively promote HSC translocation across vessel walls into the BM space. In contrast, we found that the vasculature inhibits the reverse process, as induced vascular permeability led to a rapid increase in HSCs in the blood stream. Thus, the vascular endothelium reinforces HSC localization to BM niches both by promoting HSC extravasation from blood-to-BM and by forming vascular barriers that prevent BM-to-blood escape. Our results uncouple the mechanisms that regulate the directionality of HSC trafficking and show that the vasculature can be targeted to improve hematopoietic transplantation therapies.

  14. Material Barriers to Diffusive Mixing

    Science.gov (United States)

    Haller, George; Karrasch, Daniel

    2017-11-01

    Transport barriers, as zero-flux surfaces, are ill-defined in purely advective mixing in which the flux of any passive scalar is zero through all material surfaces. For this reason, Lagrangian Coherent Structures (LCSs) have been argued to play the role of mixing barriers as most repelling, attracting or shearing material lines. These three kinematic concepts, however, can also be defined in different ways, both within rigorous mathematical treatments and within the realm of heuristic diagnostics. This has lead to a an ever-growing number of different LCS methods, each generally identifying different objects as transport barriers. In this talk, we examine which of these methods have actual relevance for diffusive transport barriers. The latter barriers are arguably the practically relevant inhibitors in the mixing of physically relevant tracers, such as temperature, salinity, vorticity or potential vorticity. We demonstrate the role of the most effective diffusion barriers in analytical examples and observational data. Supported in part by the DFG Priority Program on Turbulent Superstructures.

  15. Diabetes and diet : managing dietary barriers

    NARCIS (Netherlands)

    Friele, R.D.

    1989-01-01

    This thesis reports on the barriers diabetic patients experience with their diet, and the ways they cope with these barriers. A dietary barrier is a hinderance to a person's well-being, induced by being advised a diet. First inventories were made of possible dietary barriers and ways of

  16. Policy and network regulation for the integration of distribution generation and renewables for electricity supply

    International Nuclear Information System (INIS)

    Ten Donkelaar, M.; Van Oostvoorn, F.

    2005-08-01

    This study has analysed the existing policy and regulation aimed at the integration of an increased share of Distributed Generation (DG) in electricity supply systems in the European Union. It illustrates the state of the art and progress in the development of support mechanisms and network regulation for large-scale integration of DG. Through a benchmark study a systematic comparison has been made of different DG support schemes and distribution network regulation in EU Member States to a predefined standard, the level playing field. This level playing field has been defined as the situation where energy markets, policy and regulation provide neutral incentives to central versus distributed generation, which results in an economically more efficient electricity supply to the consumer. In current regulation and policy a certain discrepancy can be noticed between the actual regulation and policy support systems in a number of countries, the medium to long term targets and the ideal situation described according to the level playing field objective. Policies towards DG and RES are now mainly aimed at removing short-term barriers, increasing the production share of DG/RES, but often ignoring the more complex barriers of integrating DG/RES that is created by the economic network regulation in current electricity markets

  17. Barriers to healthcare for transgender individuals.

    Science.gov (United States)

    Safer, Joshua D; Coleman, Eli; Feldman, Jamie; Garofalo, Robert; Hembree, Wylie; Radix, Asa; Sevelius, Jae

    2016-04-01

    Transgender persons suffer significant health disparities and may require medical intervention as part of their care. The purpose of this manuscript is to briefly review the literature characterizing barriers to healthcare for transgender individuals and to propose research priorities to understand mechanisms of those barriers and interventions to overcome them. Current research emphasizes sexual minorities' self-report of barriers, rather than using direct methods. The biggest barrier to healthcare reported by transgender individuals is lack of access because of lack of providers who are sufficiently knowledgeable on the topic. Other barriers include: financial barriers, discrimination, lack of cultural competence by providers, health systems barriers, and socioeconomic barriers. National research priorities should include rigorous determination of the capacity of the US healthcare system to provide adequate care for transgender individuals. Studies should determine knowledge and biases of the medical workforce across the spectrum of medical training with regard to transgender medical care; adequacy of sufficient providers for the care required, larger social structural barriers, and status of a framework to pay for appropriate care. As well, studies should propose and validate potential solutions to address identified gaps.

  18. Trojan Horse Transit Contributes to Blood-Brain Barrier Crossing of a Eukaryotic Pathogen.

    Science.gov (United States)

    Santiago-Tirado, Felipe H; Onken, Michael D; Cooper, John A; Klein, Robyn S; Doering, Tamara L

    2017-01-31

    The blood-brain barrier (BBB) protects the central nervous system (CNS) by restricting the passage of molecules and microorganisms. Despite this barrier, however, the fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that is estimated to kill over 600,000 people annually. Cryptococcal infection begins in the lung, and experimental evidence suggests that host phagocytes play a role in subsequent dissemination, although this role remains ill defined. Additionally, the disparate experimental approaches that have been used to probe various potential routes of BBB transit make it impossible to assess their relative contributions, confounding any integrated understanding of cryptococcal brain entry. Here we used an in vitro model BBB to show that a "Trojan horse" mechanism contributes significantly to fungal barrier crossing and that host factors regulate this process independently of free fungal transit. We also, for the first time, directly imaged C. neoformans-containing phagocytes crossing the BBB, showing that they do so via transendothelial pores. Finally, we found that Trojan horse crossing enables CNS entry of fungal mutants that cannot otherwise traverse the BBB, and we demonstrate additional intercellular interactions that may contribute to brain entry. Our work elucidates the mechanism of cryptococcal brain invasion and offers approaches to study other neuropathogens. The fungal pathogen Cryptococcus neoformans invades the brain, causing a meningoencephalitis that kills hundreds of thousands of people each year. One route that has been proposed for this brain entry is a Trojan horse mechanism, whereby the fungus crosses the blood-brain barrier (BBB) as a passenger inside host phagocytes. Although indirect experimental evidence supports this intriguing mechanism, it has never been directly visualized. Here we directly image Trojan horse transit and show that it is regulated independently of free fungal entry, contributes

  19. 24 CFR 574.645 - Coastal barriers.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Coastal barriers. 574.645 Section....645 Coastal barriers. In accordance with the Coastal Barrier Resources Act, 16 U.S.C. 3501, no financial assistance under this part may be made available within the Coastal Barrier Resources System. ...

  20. Socio-technical inertia: Understanding the barriers to electric vehicles

    International Nuclear Information System (INIS)

    Steinhilber, Simone; Wells, Peter; Thankappan, Samarthia

    2013-01-01

    It is widely accepted that electrification of the transport sector is one of several technological trajectories that could redress some of the environmental issues associated with the growth in travel demand including climate change and oil demand at a global scale, and air quality and noise pollution at the urban scale. Electric vehicles have been considered a promising technology at repeated intervals over the last century, but this promise has not been realised. This paper is a contribution to understanding the key tools and strategies that might enable the successful introduction of new technologies and innovations by exploring the key barriers to electric vehicles encountered in two countries (UK and Germany) where the automobile industry has been historically significant. The study evaluates stakeholders' opinions on relevant regulation, infrastructure investment, R and D incentives, and consumer incentives. The key findings of the research are that the introduction and penetration of EVs is confronted by several barriers that inhibit a larger market penetration under current conditions, which in turn casts doubt on the assumptions of strategic niche management and transitions theory. - Highlights: • Immature developing technology reason behind non-commercialisation of EVs. • EVs currently do not present a significant benefit to the electricity sector. • EVs rely on a mix of regulatory and government measures for their development. • EVs face lock-in problem of unsustainable technologies and related barriers. • Positive milieu for innovation in vehicle technology and business models are required

  1. A comparison of freeway median crash frequency, severity, and barrier strike outcomes by median barrier type.

    Science.gov (United States)

    Russo, Brendan J; Savolainen, Peter T

    2018-08-01

    Median-crossover crashes are among the most hazardous events that can occur on freeways, often resulting in severe or fatal injuries. The primary countermeasure to reduce the occurrence of such crashes is the installation of a median barrier. When installation of a median barrier is warranted, transportation agencies are faced with the decision among various alternatives including concrete barriers, beam guardrail, or high-tension cable barriers. Each barrier type differs in terms of its deflection characteristics upon impact, the required installation and maintenance costs, and the roadway characteristics (e.g., median width) where installation would be feasible. This study involved an investigation of barrier performance through an in-depth analysis of crash frequency and severity data from freeway segments where high-tension cable, thrie-beam, and concrete median barriers were installed. A comprehensive manual review of crash reports was conducted to identify crashes in which a vehicle left the roadway and encroached into the median. This review also involved an examination of crash outcomes when a barrier strike occurred, which included vehicle containment, penetration, or re-direction onto the travel lanes. The manual review of crash reports provided critical supplementary information through narratives and diagrams not normally available through standard fields on police crash report forms. Statistical models were estimated to identify factors that affect the frequency, severity, and outcomes of median-related crashes, with particular emphases on differences between segments with varying median barrier types. Several roadway-, traffic-, and environmental-related characteristics were found to affect these metrics, with results varying across the different barrier types. The results of this study provide transportation agencies with important guidance as to the in-service performance of various types of median barrier. Copyright © 2018 Elsevier Ltd. All rights

  2. Protective barrier development: Overview

    International Nuclear Information System (INIS)

    Wing, N.R.; Gee, G.W.

    1990-01-01

    Protective barrier and warning marker systems are being developed to isolate wastes disposed of near the earth's surface at the Hanford Site. The barrier is designed to function in an arid to semiarid climate, to limit infiltration and percolation of water through the waste zone to near-zero, to be maintenance free, and to last up to 10,000 yr. Natural materials (e.g., fine soil, sand, gravel, riprap, clay, asphalt) have been selected to optimize barrier performance and longevity and to create an integrated structure with redundant features. These materials isolate wastes by limiting water drainage; reducing the likelihood of plant, animal, and human intrusion; controlling emission of noxious gases; and minimizing erosion. Westinghouse Hanford Company and Pacific Northwest Laboratory efforts to assess the performance of various barrier and marker designs will be discussed

  3. [Barriers to Digitalisation of Healthcare in Germany: A Survey of Experts].

    Science.gov (United States)

    Nohl-Deryk, Pascal; Brinkmann, Jesaja Kenneth; Gerlach, Ferdinand Michael; Schreyögg, Jonas; Achelrod, Dmitrij

    2018-01-04

    Digital health is a growing area in healthcare with a huge potential. Nevertheless, the degree of digitalization in German healthcare is low when compared internationally and with other German industries. Despite political efforts, certain barriers seem to strongly impede the process of digitalization process in healthcare. We surveyed 18 representative healthcare experts from various sectors with semi-structured interviews on barriers and solutions for digital health. Thematic analysis by Braun and Clarke was used for interpretation. The interviewees identified barriers that were stakeholder-specific and across stakeholders. Self-regulatory bodies and the medical profession were found to lack willingness and organizational structure for digitalization. Lack of evidence and missing interoperability represented primary obstacles, while current legislation and financial regulations were rarely mentioned. In particular, infrastructure expansion and interoperability would require a coordinated, state intervention. Positive communication on possibilities and benefits of digital solutions was also considered important. A strong political will, an overarching strategy accompanied by a communication concept seems to be necessary in order for digital health to succeed. Regarding legislation, binding specifications, deadlines and sanctions may be needed for self-regulatory bodies, while also involving users in the development process at an early stage and creating positive incentives for using digital solutions. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Addressing barriers to low carbon energy

    International Nuclear Information System (INIS)

    Berry, Fiona; Dunstan, Chris

    2012-01-01

    Full text: Two energy solutions gaining attention are cogeneration and trigeneration, mostly fuelled by natural gas, although other renewable sources can be used, such as sewage, agricultural waste and municipal waste. Trigeneration has become increasingly popular in Australia's urban centres as a relatively cost-effective means to cut the carbon-intensity of energy supply by more than half compared to traditional coal- fired electricity. Some examples of trigeneration projects include the City of Sydney's planned 360 megawatt trigeneration networks by 2030, the University of Technology Sydney's campus master plan and the six star Green Star Commonwealth Bank Place building in Sydney. Trigeneration and cogeneration can present opportunities such as addressing the issue of rising peak demand, which is a major driver for the current $9 billion per annum of network infrastructure spending. They can also face barriers. For example, depending on the current state of the network, additional network costs can be required to accommodate trigeneration. Furthermore, under the current National Electricity Market regulations and conventions, challenges do exist to timely and financially viable connection to the grid. Here we present two examples of barriers to trigeneration and cogeneration and solutions being considered and implemented. The University of Technology Sydney campus master plan is underway, with approximately 100,000sq.m of floor area being built by 2019 and includes plans for trigeneration. During the master planning phase of development, the university considered small trigeneration units in individual buildings in order to reduce the carbon intensity of electricity supply and deliver high ratings under Green Star ratings. When considering connecting trigeneration with the grid at multiple buildings on an individual basis, a number of barriers were encountered by UTS. The largest barrier was appropriate charging for connecting to and using the grid. However

  5. Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balance.

    Science.gov (United States)

    Choi, Eun-Ju; Debnath, Trishna; Tang, Yujiao; Ryu, Young-Bae; Moon, Sang-Ho; Kim, Eun-Kyung

    2016-12-01

    Moringa oleifera (M. oleifera) is widely cultivated in tropical and subtropical regions and has been used as a vegetable and in traditional medicine. In this study, the anti-atopic dermatitis activity of the ethanol extract of M. oleifera leaf was investigated in vitro and in vivo. For the in vitro study, HaCaT human keratinocytes were used for cytokines and MAPKinase assay. In the in vivo study, M. oleifera leaf ethanolic extract (MO) was topically applied to BALB/c mice with Dermatophagoides farinae extract (DFE; house dust mite extract)- and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). The expression of TNF-α, CCL17, IL-1β, IL-6 pro-inflammatory cytokine-related mRNA, and mitogen-activated protein kinases (MAPKs) in TNF-α/IFN-γ-induced HaCaT keratinocytes were reduced by MO. Epidermal and dermal ear thickness, mast cell infiltration, serum immunoglobulin levels, as well as gene expression of various cytokines in the ear tissue, lymph nodes, and splenocytes were improved by treatment with MO. In addition, MO reduced the expression of retinoic acid-related orphan receptor γT (RORγT), thymic stromal lymphopoietin (TSLP), and mannose receptor (CD206) mRNA in the ear tissue and improved cervical lymph node size. The results of this study strongly suggest the beneficial effects of MO on AD via the regulation of inflammatory responses. Copyright © 2016. Published by Elsevier Masson SAS.

  6. Fusion barriers in heavy ion collisions

    International Nuclear Information System (INIS)

    Zhu Long; Su Jun; Xie Wenjie; Guo Chenchen; Zhang Donghong; Zhang Fengshou

    2014-01-01

    Study of fusion barrier is very important for people to better understand fusion reactions. In this paper the Improved Isospin-dependent Quantum Molecular Dynamics (ImIQMD) model is introduced firstly. Then the shell correction effects, energy dependence, isospin effects and orientation effects of fusion barrier are studied. The fusion barriers for the fusion reactions "4"0Ca + "4"0Ca, "4"8Ca + "2"0"8Pb, "4"8Ca + "2"0"4Pb and "1"6O + "1"5"4Sm are extracted. The negative shell correction energies lower potential barriers of a certain reaction. A complex phenomenon of energy dependence is observed. It is also found that incident energy dependence of the barrier radius and barrier height shows opposite behaviors. The Coulomb potential shows weak energy dependence when distance of two colliding nuclei is lower than the touching distance. The isospin effects of the potential barrier are investigated. The orientation effects of the potential barrier are also discussed for the system "1"6O + "1"5"4Sm. (authors)

  7. Effect of joint mechanism on vehicle redirectional capability of water-filled road safety barrier systems.

    Science.gov (United States)

    Thiyahuddin, M I; Thambiratnam, D P; Gu, Y T

    2014-10-01

    Portable water-filled barriers (PWFBs) are roadside appurtenances that prevent vehicles from penetrating into temporary construction zones on roadways. PWFBs are required to satisfy the strict regulations for vehicle re-direction in tests. However, many of the current PWFBs fail to re-direct the vehicle at high speeds due to the inability of the joints to provide appropriate stiffness. The joint mechanism hence plays a crucial role in the performance of a PWFB system at high speed impacts. This paper investigates the desired features of the joint mechanism in a PWFB system that can re-direct vehicles at high speeds, while limiting the lateral displacement to acceptable limits. A rectangular "wall" representative of a 30m long barrier system was modeled and a novel method of joining adjacent road barriers was introduced through appropriate pin-joint connections. The impact response of the barrier "wall" and the vehicle was obtained and the results show that a rotational stiffness of 3000kNm/rad at the joints seems to provide the desired features of the PWFB system to re-direct impacting vehicles and restrict the lateral deflection. These research findings will be useful to safety engineers and road barrier designers in developing a new generation of PWFBs for increased road safety. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Transcriptome analysis of the ependymal barrier during murine neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Mishra Pramod

    2012-06-01

    Full Text Available Abstract Background Central nervous system (CNS barriers play a pivotal role in the protection and homeostasis of the CNS by enabling the exchange of metabolites while restricting the entry of xenobiotics, blood cells and blood-borne macromolecules. While the blood–brain barrier and blood-cerebrospinal fluid barrier (CSF control the interface between the blood and CNS, the ependyma acts as a barrier between the CSF and parenchyma, and regulates hydrocephalic pressure and metabolic toxicity. Neurocysticercosis (NCC is an infection of the CNS caused by the metacestode (larva of Taenia solium and a major cause of acquired epilepsy worldwide. The common clinical manifestations of NCC are seizures, hydrocephalus and symptoms due to increased intracranial pressure. The majority of the associated pathogenesis is attributed to the immune response against the parasite. The properties of the CNS barriers, including the ependyma, are affected during infection, resulting in disrupted homeostasis and infiltration of leukocytes, which correlates with the pathology and disease symptoms of NCC patients. Results In order to characterize the role of the ependymal barrier in the immunopathogenesis of NCC, we isolated ependymal cells using laser capture microdissection from mice infected or mock-infected with the closely related parasite Mesocestoides corti, and analyzed the genes that were differentially expressed using microarray analysis. The expression of 382 genes was altered. Immune response-related genes were verified by real-time RT-PCR. Ingenuity Pathway Analysis (IPA software was used to analyze the biological significance of the differentially expressed genes, and revealed that genes known to participate in innate immune responses, antigen presentation and leukocyte infiltration were affected along with the genes involved in carbohydrate, lipid and small molecule biochemistry. Further, MHC class II molecules and chemokines, including CCL12, were found

  9. A novel transgenic zebrafish model for blood-brain and blood-retinal barrier development

    Directory of Open Access Journals (Sweden)

    Sugimoto Masahiko

    2010-07-01

    Full Text Available Abstract Background Development and maintenance of the blood-brain and blood-retinal barrier is critical for the homeostasis of brain and retinal tissue. Despite decades of research our knowledge of the formation and maintenance of the blood-brain (BBB and blood-retinal (BRB barrier is very limited. We have established an in vivo model to study the development and maintenance of these barriers by generating a transgenic zebrafish line that expresses a vitamin D-binding protein fused with enhanced green fluorescent protein (DBP-EGFP in blood plasma, as an endogenous tracer. Results The temporal establishment of the BBB and BRB was examined using this transgenic line and the results were compared with that obtained by injection of fluorescent dyes into the sinus venosus of embryos at various stages of development. We also examined the expression of claudin-5, a component of tight junctions during the first 4 days of development. We observed that the BBB of zebrafish starts to develop by 3 dpf, with expression of claudin-5 in the central arteries preceding it at 2 dpf. The hyaloid vasculature in the zebrafish retina develops a barrier function at 3 dpf, which endows the zebrafish with unique advantages for studying the BRB. Conclusion Zebrafish embryos develop BBB and BRB function simultaneously by 3 dpf, which is regulated by tight junction proteins. The Tg(l-fabp:DBP-EGFP zebrafish will have great advantages in studying development and maintenance of the blood-neural barrier, which is a new application for the widely used vertebrate model.

  10. Economic alternatives for containment barriers

    International Nuclear Information System (INIS)

    Nicholson, P.J.; Jasperse, B.H.; Fisher, M.J.

    1997-01-01

    Fixation, barriers, and containment of existing landfills and other disposal areas are often performed by insitu auger type soil mixing and jet grouting. Cement or other chemical reagents are mixed with soil to form both vertical and horizontal barriers. Immobilization of contaminants can be economically achieved by mixing soil and the contaminants with reagents that solidify or stabilize the contaminated area. Developed in Japan, and relatively new to the United States, the first large scale application was for a vertical barrier at the Jackson Lake Dam project in 1986. This technology has grown in both the civil and environmental field since. The paper describes current United States practice for Deep Soil Mixing (over 12 meters in depth), and Shallow Soil Mixing for vertical barriers and stabilization/solidification, and Jet Grouting for horizontal and vertical barriers. Creating very low permeability barriers at depth with minimal surface return often makes these techniques economical when compared to slurry trenches. The paper will discuss equipment, materials, soil and strength parameters, and quality control

  11. A Call for Barriers in Implementation of Education Regulation: The Latest English Textbook as Main Instructional Media in Schools in Indonesia

    Directory of Open Access Journals (Sweden)

    Fadel Muslaini

    2018-05-01

    Full Text Available Education in Indonesia is much influenced by the implementation of the latest curriculum namely 2013 curriculum with integrated skills approach. The implementation condition must be overseen through time to measure how effective the progress and the result are. To find out the condition, this study involved the teacher and students in the implementation of this issue to find out their perspective and their experience in the real condition of learning process. This paper explores the significant impact of implementation policy in the textbook in Indonesia as the main instructional media applied in the entire country. This study on the other hand tried to reveal the authentic condition in the process of learning and teaching by focusing on English materials. Both quantitative and qualitative methods were used in the process of data collection. This research found many barriers faced by the teacher and students in the policy implementation of textbook in the school as the national sample. The special purposes and the local situation influenced a lot the impact of this country-scale regulation. This study result is expected to provide additional information and evidence to fulfill the aim of the learning process effectively in the future that will be beneficial for authority of education policy, teachers, students, organization, and etc.

  12. Loss of guanylyl cyclase C (GCC signaling leads to dysfunctional intestinal barrier.

    Directory of Open Access Journals (Sweden)

    Xiaonan Han

    2011-01-01

    Full Text Available Guanylyl Cyclase C (GCC signaling via uroguanylin (UGN and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function.Paracellular permeability of intestinal segments was assessed in wild type (WT and GCC deficient (GCC-/- mice with and without lipopolysaccharide (LPS challenge, as well as in UGN deficient (UGN-/- mice. IFNγ and myosin light chain kinase (MLCK levels were determined by real time PCR. Expression of tight junction proteins (TJPs, phosphorylation of myosin II regulatory light chain (MLC, and STAT1 activation were examined in intestinal epithelial cells (IECs and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi. We found that intestinal permeability was increased in GCC-/- and UGN-/- mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC-/- mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC-/- and UGN-/- mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability.GCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury.

  13. “Engelsiz Şehir” Kavramı Açısından Malatya (Malatya From The Perspective Of “Barrier-Free City” Concept

    Directory of Open Access Journals (Sweden)

    Gülizar ÇAKIR SÜMER

    2015-06-01

    Full Text Available Demand of barrier-free cities is a part of human rights and meeting of this demand is one of the main responsibility areas of administrations. Even it exists legal regulations on establishing barrier-free cities in Turkey, the problem is mostly about practice of these regulations. This study aims at exerting that the structure providing integration of the disabled to the city is inadequate on the ground of Malatya city center. To this end, it has been tried to be determined whether urban accesories, substructure, public buildings are appropriate or not for access of the disabled, and the present situation has been analysed from the perspective of "barrier-free city" concept. After the survey performed, in context of developing city planning perception, it has been determined that even there have been positive progress on eliminating the obstacles which are faced by the disabled at country life, problems and deficiencies still go on. In this sense, many of the buildings and services are far away from being accessible by the disabled.

  14. Converse Barrier Certificate Theorem

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2013-01-01

    This paper presents a converse barrier certificate theorem for a generic dynamical system.We show that a barrier certificate exists for any safe dynamical system defined on a compact manifold. Other authors have developed a related result, by assuming that the dynamical system has no singular...... points in the considered subset of the state space. In this paper, we redefine the standard notion of safety to comply with generic dynamical systems with multiple singularities. Afterwards, we prove the converse barrier certificate theorem and illustrate the differences between ours and previous work...

  15. Inclusive design drivers and barriers – a manufacturing perspective from Pakistan

    Directory of Open Access Journals (Sweden)

    Amjad Hussain

    2015-01-01

    Full Text Available The demographics of older people and people with disabilities in developing countries are discussed in the context of inclusive design and the drivers and barriers to inclusive design have been identified. Data were collected from 50 individuals from various industrial sectors in Pakistan. Corporate social responsibility (CSR relates to inclusive aspects of products, but most respondents either did not know about CSR or did not have a CSR post in their organizations, but 64% had awareness of inclusive design terminology. The study concluded that motivation through social responsibility; innovation and differentiation; demographics and consumer trends; brand enhancement; customer satisfaction; new market opportunity; and legislation were the perceived drivers for manufacturers in Pakistan. Most respondents felt that lack of resources and guidance, lack of awareness about inclusive design, difficulty in changing the business culture, lack of government regulations, and the perception that inclusive design is expensive were the most significant barriers.

  16. Tunnel superpenetrability of potential barriers

    International Nuclear Information System (INIS)

    Zakhariev, B N.

    1982-01-01

    The transmission of two particles through the same barrier is considered. The limiting cases are compared when the particles are joined together in a single particle with double mass-energy and potential and when they pass the barrier independently. As an intermediate case a pair of particles bound in a quasideuteron of a finite size is considered. It is shown that long-range collective correlations of particles (of the superfluidity type and others) simplify very much for them passing through high potential barriers. This happens due to the transfer of the additional energy from the particles outside the barriers to those inside it

  17. Barrier rf systems in synchrotrons

    International Nuclear Information System (INIS)

    Bhat, Chandra M.

    2004-01-01

    Recently, many interesting applications of the barrier RF system in hadron synchrotrons have been realized. A remarkable example of this is the development of longitudinal momentum mining and implementation at the Fermilab Recycler for extraction of low emittance pbars for the Tevatron shots. At Fermilab, we have barrier RF systems in four different rings. In the case of Recycler Ring, all of the rf manipulations are carried out using a barrier RF system. Here, the author reviews various uses of barrier rf systems in particle accelerators including some new schemes for producing intense proton beam and possible new applications

  18. Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases

    NARCIS (Netherlands)

    Shikhagaie, Medya M.; Germar, Kristine; Bal, Suzanne M.; Ros, Xavier Romero; Spits, Hergen

    2017-01-01

    Innate lymphoid cells (ILCs) are important in the regulation of barrier homeostasis. These cells do not express T cell receptors but share many functional similarities with T helper cells and cytotoxic CD8(+) T lymphocytes. ILCs are divided into three groups, namely group 1 ILCs, group 2 ILCs and

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

    Directory of Open Access Journals (Sweden)

    William J Joiner

    Full Text Available 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.

  20. Subsurface barrier verification technologies, informal report

    International Nuclear Information System (INIS)

    Heiser, J.H.

    1994-06-01

    One of the more promising remediation options available to the DOE waste management community is subsurface barriers. Some of the uses of subsurface barriers include surrounding and/or containing buried waste, as secondary confinement of underground storage tanks, to direct or contain subsurface contaminant plumes and to restrict remediation methods, such as vacuum extraction, to a limited area. To be most effective the barriers should be continuous and depending on use, have few or no breaches. A breach may be formed through numerous pathways including: discontinuous grout application, from joints between panels and from cracking due to grout curing or wet-dry cycling. The ability to verify barrier integrity is valuable to the DOE, EPA, and commercial sector and will be required to gain full public acceptance of subsurface barriers as either primary or secondary confinement at waste sites. It is recognized that no suitable method exists for the verification of an emplaced barrier's integrity. The large size and deep placement of subsurface barriers makes detection of leaks challenging. This becomes magnified if the permissible leakage from the site is low. Detection of small cracks (fractions of an inch) at depths of 100 feet or more has not been possible using existing surface geophysical techniques. Compounding the problem of locating flaws in a barrier is the fact that no placement technology can guarantee the completeness or integrity of the emplaced barrier. This report summarizes several commonly used or promising technologies that have been or may be applied to in-situ barrier continuity verification

  1. Fluctuations in Schottky barrier heights

    International Nuclear Information System (INIS)

    Mahan, G.D.

    1984-01-01

    A double Schottky barrier is often formed at the grain boundary in polycrystalline semiconductors. The barrier height is shown to fluctuate in value due to the random nature of the impurity positions. The magnitude of the fluctuations is 0.1 eV, and the fluctuations cause the barrier height measured by capacitance to differ from the one measured by electrical conductivity

  2. Effect of small-sided team sport training and protein intake on muscle mass, physical function and markers of health in older untrained adults: A randomized trial.

    Science.gov (United States)

    Vorup, Jacob; Pedersen, Mogens Theisen; Brahe, Lena Kirchner; Melcher, Pia Sandfeld; Alstrøm, Joachim Meno; Bangsbo, Jens

    2017-01-01

    The effect of small-sided team sport training and protein intake on muscle mass, physical function, and adaptations important for health in untrained older adults was examined. Forty-eight untrained older (72±6 (±standard deviation, SD) years men and women were divided into either a team sport group ingesting a drink high in protein (18 g) immediately and 3 h after each training session (TS-HP, n = 13), a team sport group ingesting an isocaloric drink with low protein content (3 g; TS-LP, n = 18), or a control group continuing their normal activities (CON, n = 17). The team sport training was performed as ~20 min of small-sided ball games twice a week over 12 weeks. After the intervention period, leg muscle mass was 0.6 kg higher (P = 0.047) in TS-HP, with no effect in TS-LP. In TS-HP, number of sit-to-stand repetitions increased (1.2±0.6, P = 0.054), time to perform 2.45 m up-and-go was lower (0.7±0.3 s, P = 0.03) and number of arm curl repetitions increased (3.5±1.2, P = 0.01), whereas in TS-LP only number of repetitions in sit-to-stand was higher (1.6±0.6, P = 0.01). In TS-LP, reductions were observed in total and abdominal fat mass (1.2±0.5 and 0.4±0.2 kg, P = 0.03 and P = 0.02, respectively), heart rate at rest (9±3 bpm, P = 0.002) and plasma C-reactive protein (1.8±0.8 mmol/L, P = 0.03), with no effects in TS-HP. Thus, team sport training improves functional capacity of untrained older adults and increases leg muscle mass only when ingesting proteins after training. Furthermore, team sport training followed by intake of drink with low protein content does lower fat mass, heart rate at rest and level of systemic inflammation. clinicaltrials.gov NCT03120143.

  3. Converse Barrier Certificate Theorems

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2016-01-01

    This paper shows that a barrier certificate exists for any safe dynamical system. Specifically, we prove converse barrier certificate theorems for a class of structurally stable dynamical systems. Other authors have developed a related result by assuming that the dynamical system has neither...

  4. Barrier inhomogeneities limited current and 1/f noise transport in GaN based nanoscale Schottky barrier diodes

    Science.gov (United States)

    Kumar, Ashutosh; Heilmann, M.; Latzel, Michael; Kapoor, Raman; Sharma, Intu; Göbelt, M.; Christiansen, Silke H.; Kumar, Vikram; Singh, Rajendra

    2016-01-01

    The electrical behaviour of Schottky barrier diodes realized on vertically standing individual GaN nanorods and array of nanorods is investigated. The Schottky diodes on individual nanorod show highest barrier height in comparison with large area diodes on nanorods array and epitaxial film which is in contrast with previously published work. The discrepancy between the electrical behaviour of nanoscale Schottky diodes and large area diodes is explained using cathodoluminescence measurements, surface potential analysis using Kelvin probe force microscopy and 1ow frequency noise measurements. The noise measurements on large area diodes on nanorods array and epitaxial film suggest the presence of barrier inhomogeneities at the metal/semiconductor interface which deviate the noise spectra from Lorentzian to 1/f type. These barrier inhomogeneities in large area diodes resulted in reduced barrier height whereas due to the limited role of barrier inhomogeneities in individual nanorod based Schottky diode, a higher barrier height is obtained. PMID:27282258

  5. E-cadherin Is Critical for Collective Sheet Migration and Is Regulated by the Chemokine CXCL12 Protein During Restitution*

    Science.gov (United States)

    Hwang, Soonyean; Zimmerman, Noah P.; Agle, Kimberle A.; Turner, Jerrold R.; Kumar, Suresh N.; Dwinell, Michael B.

    2012-01-01

    Chemokines and other immune mediators enhance epithelial barrier repair. The intestinal barrier is established by highly regulated cell-cell contacts between epithelial cells. The goal of these studies was to define the role for the chemokine CXCL12 in regulating E-cadherin during collective sheet migration during epithelial restitution. Mechanisms regulating E-cadherin were investigated using Caco2BBE and IEC-6 model epithelia. Genetic knockdown confirmed a critical role for E-cadherin in in vitro restitution and in vivo wound repair. During restitution, both CXCL12 and TGF-β1 tightened the monolayer by decreasing the paracellular space between migrating epithelial cells. However, CXCL12 differed from TGF-β1 by stimulating the significant increase in E-cadherin membrane localization during restitution. Chemokine-stimulated relocalization of E-cadherin was paralleled by an increase in barrier integrity of polarized epithelium during restitution. CXCL12 activation of its cognate receptor CXCR4 stimulated E-cadherin localization and monolayer tightening through Rho-associated protein kinase activation and F-actin reorganization. These data demonstrate a key role for E-cadherin in intestinal epithelial restitution. PMID:22549778

  6. Richards Barrier LA Reference Design Feature Evaluation

    International Nuclear Information System (INIS)

    N.E. Kramer

    1999-01-01

    The Richards Barrier is one of the design features of the repository to be considered for the License Application (LA), Richards was a soil scientist who first described the diversion of moisture between two materials with different hydrologic properties. In this report, a Richards Barrier is a special type of backfill with a fine-grained material (such as sand) overlaying a coarse-grained material (such as gravel). Water that enters an emplacement drift will first encounter the fine-grained material and be transported around the coarse-grained material covering the waste package, thus protecting the waste package from contact with most of the groundwater. The objective of this report is to discuss the benefits and liabilities to the repository by the inclusion of a Richards Barrier type backfill in emplacement drifts. The Richards Barrier can act as a barrier to water flow, can reduce the waste package material dissolution rate, limit mobilization of the radionuclides, and can provide structural protection for the waste package. The scope of this report is to: (1) Analyze the behavior of barrier materials following the intrusion of groundwater for influxes of 1 to 300 mm per year. The report will demonstrate diversion of groundwater intrusions into the barrier over an extended time period when seismic activity and consolidation may cause the potential for liquefaction and settlement of the Richards Barrier. (2) Review the thermal effects of the Richards Barrier on material behavior. (3) Analyze the effect of rockfall on the performance of the Richards Barrier and the depth of the barrier required to protect waste packages under the barrier. (4) Review radiological and heating conditions on placement of multiple layers of the barrier. Subsurface Nuclear Safety personnel will perform calculations to determine the radiation reduction-time relationship and shielding capacity of the barrier. (5) Evaluate the effects of ventilation on cooling of emplacement drifts and

  7. Skin barrier composition

    International Nuclear Information System (INIS)

    Osburn, F.G.

    1985-01-01

    A skin barrier composition comprises a mixture of a copolymer resin of ethylene and vinyl acetate (EVA), and a water-insoluble dry tack-providing elastomer such as polyisobutylene. The composition after mixing and molding, is subjected to ionizing irradiation to form cross-linked polymer networks of the EVA. The compositions have exceptional properties for use as barrier sheets, rings, or strips in ostomy, wound drainage, and incontinence devices. (author)

  8. Skin barrier composition

    Energy Technology Data Exchange (ETDEWEB)

    Osburn, F G

    1985-06-12

    A skin barrier composition comprises a mixture of a copolymer resin of ethylene and vinyl acetate (EVA), and a water-insoluble dry tack-providing elastomer such as polyisobutylene. The composition after mixing and molding, is subjected to ionizing irradiation to form cross-linked polymer networks of the EVA. The compositions have exceptional properties for use as barrier sheets, rings, or strips in ostomy, wound drainage, and incontinence devices.

  9. Modulation of Mrp1 (ABCc1 and Pgp (ABCb1 by bilirubin at the blood-CSF and blood-brain barriers in the Gunn rat.

    Directory of Open Access Journals (Sweden)

    Silvia Gazzin

    2011-01-01

    Full Text Available Accumulation of unconjugated bilirubin (UCB in the brain causes bilirubin encephalopathy. Pgp (ABCb1 and Mrp1 (ABCc1, highly expressed in the blood-brain barrier (BBB and blood-cerebrospinal fluid barrier (BCSFB respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj Gunn rats compared to heterozygous, not jaundiced (Jj littermates at different developmental stages (2, 9, 17 and 60 days after birth. BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16-27% of adult values, despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17-P60, respectively; Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60-70% of the adult values in both jj and Jj at P2, but was markedly (50% down-regulated in jj pups starting at P9, particularly in the 4(th ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity.

  10. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    2014-01-01

    BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...... this study, we recommend promoting recess physical activity through a combination of actions, addressing barriers within the natural, social, physical and organizational environment....

  11. Barriers to teaching ocean science in Greek schools

    Science.gov (United States)

    Papathanassiou, Martha; McHugh, Patricia; Domegan, Christine; Gotensparre, Susan; Fauville, Geraldine; Parr, Jon

    2017-04-01

    total, 13 stakeholders participated in the event, consisting of Incumbents, Challengers and Regulating agencies. The aim of this consultation was to gain a deep insight into stakeholders' barriers, attitudes and perceptions towards teaching 12-19 years olds about the ocean. The Greek education stakeholders identified 41 barriers in seven different categories to teaching 12-19 year olds about the ocean. Lastly, 18 options were proposed in order to overcome these barriers.

  12. Transportation Energy Futures Series: Non-Cost Barriers to Consumer Adoption of New Light-Duty Vehicle Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, T.

    2013-03-01

    Consumer preferences are key to the adoption of new vehicle technologies. Barriers to consumer adoption include price and other obstacles, such as limited driving range and charging infrastructure; unfamiliarity with the technology and uncertainty about direct benefits; limited makes and models with the technology; reputation or perception of the technology; standardization issues; and regulations. For each of these non-cost barriers, this report estimates an effective cost and summarizes underlying influences on consumer preferences, approximate magnitude and relative severity, and assesses potential actions, based on a comprehensive literature review. While the report concludes that non-cost barriers are significant, effective cost and potential market share are very uncertain. Policies and programs including opportunities for drivers to test drive advanced vehicles, general public outreach and information programs, incentives for providing charging and fueling infrastructure, and development of technology standards were examined for their ability to address barriers, but little quantitative data exists on the effectiveness of these measures. This is one in a series of reports produced as a result of the Transportation Energy Futures project, a Department of Energy-sponsored multi-agency effort to pinpoint underexplored strategies for reducing GHGs and petroleum dependence related to transportation.

  13. Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9.

    Science.gov (United States)

    Wu, Jitao; Zhao, Duo; Wu, Shuang; Wang, Dan

    2015-02-05

    Cerebrovascular disease (CVD) ranks as the top three health risks, specially cerebral ischemia characterized with the damage of blood-brain barrier (BBB). The angiotensin Ang-(1-7) was proven to have a protective effect on cerebrovascular diseases. However, its role on blood-brain barrier and the underlying molecular mechanism remains unclear. In this study, Ang-(1-7) significantly relieved damage of ischemia reperfusion injury on blood-brain barrier in cerebral ischemia reperfusion injury (IRI) rats. Furthermore, its treatment attenuated BBB permeability and brain edema. Similarly, Ang-(1-7) also decreased the barrier permeability of brain endothelial cell line RBE4. Further analysis showed that Ang-(1-7) could effectively restore tight junction protein (claudin-5 and zonula occludens ZO-1) expression levels both in IRI-rats and hypoxia-induced RBE4 cells. Furthermore, Ang-(1-7) stimulation down-regulated hypoxia-induced matrix metalloproteinase-9 (MMP-9) levels, whose silencing with (matrix metalloproteinase-9 hemopexin domain) MMP9-PEX inhibitor significantly increased the expression of claudin-5 and ZO-1. Further mechanism analysis demonstrated that Ang-(1-7) might junction protein levels by tissue inhibitor of metalloproteinase 1 (TIMP1)-MMP9 pathway, because Ang-(1-7) enhanced TIMP1 expression, whose silencing obviously attenuated the inhibitor effect of Ang-(1-7) on MMP-9 levels and decreased Ang-(1-7)-triggered increase in claudin-5 and ZO-1. Together, this study demonstrated a protective role of Ang-(1-7) in IRI-induced blood-brain barrier damage by TIMP1-MMP9-regulated tight junction protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic agent against IRI and its complications. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Sub-barrier fusion and near-barrier quasi-elastic scattering

    International Nuclear Information System (INIS)

    Kolata, J.J.; Tighe, R.J.

    1990-01-01

    Elastic scattering of 32 S on 58,64 Ni and fusion of 32 S+ 58,64 Ni and 34 S+ 64 Ni have been measured at energies near the Coulomb barrier. Our results differ in several important respects from previous measurements on these systems. Coupled-channels calculations which explicitly allow for inelastic excitation and single-nucleon transfer reproduce the main features of the new data. Near-barrier elastic scattering of 48 Ca on 40 Ca has also been measured. These data provide evidence for the effect of strong coupling to positive Q-value channels other than single-nucleon transfer. 18 refs., 3 figs

  15. Identifying barriers to emergency care services.

    Science.gov (United States)

    Cannoodt, Luk; Mock, Charles; Bucagu, Maurice

    2012-01-01

    This paper aims to present a review of published evidence of barriers to emergency care, with attention towards both financial and other barriers. With the keywords (financial) accessibility, barriers and emergency care services, citations in PubMed were searched and further selected in the context of the objective of this article. Forty articles, published over a period of 15 years, showed evidence of significant barriers to emergency care. These barriers often tend to persist, despite the fact that the evidence was published many years ago. Several publications stressed the importance of the financial barriers in foregoing or delaying potentially life-saving emergency services, both in poor and rich countries. Other publications report non-financial barriers that prevent patients in need of emergency care (pre-hospital and in-patient care) from seeking care, from arriving in the proper emergency department without undue delay or from receiving proper treatment when they do arrive in these departments. It is clear that timely access to life-saving and disability-preventing emergency care is problematic in many settings. Yet, low-cost measures can likely be taken to significantly reduce these barriers. It is time to make an inventory of these measures and to implement the most cost-effective ones worldwide. Copyright © 2011 John Wiley & Sons, Ltd.

  16. Cryogenic Barrier Demonstration Project. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, L.A.; Yarmak, E.; Long, E.L.

    2000-03-01

    A long-term frozen soil barrier was implemented at the HRE (Homogeneous Reactor Experiment) Pond facility at the Oak Ridge National Laboratory in 1997. This was performed to verify the technical feasibility and costs of deploying a frozen barrier at a radiologically contaminated site. Work began in September 1996 and progressed through to December 1999. The frozen barrier has been operational since November 1997. Verification of the barrier integrity was performed independently by the EPA's SITE Program. This project showed frozen barriers offer a proven technology to retain below grade hazardous substances at relatively low costs with minimal effect on the environment.

  17. One and done: Reasons principal investigators conduct only one FDA-regulated drug trial

    Directory of Open Access Journals (Sweden)

    Amy Corneli, PhD, MPH

    2017-06-01

    Full Text Available Concerns have been raised over the high turnover rate for clinical investigators. Using the U.S. Food and Drug Administration's (FDA Bioresearch Monitoring Information System database, we conducted an online survey to identify factors that affect principal investigators' (PIs decisions to conduct only a single FDA-regulated drug trial. Of the 201 PIs who responded, 54.2% were classified as “one-and-done.” Among these investigators, 28.9% decided for personal reasons to not conduct another trial, and 44.4% were interested in conducting another trial, but no opportunities were available. Three categories of broad barriers were identified as generally burdensome or challenging by the majority of investigators: 1 workload balance (balancing trial implementation with other work obligations and opportunities (63.8%; 2 time requirements (time to initiate and implement trial; investigator and staff time (63.4%; and 3 data and safety reporting (56.5%. Additionally, 46.0% of investigators reported being generally unsatisfied with finance-related issues. These same top three barriers also affected investigators' decisions to no longer conduct FDA-regulated trials. Our findings illuminate three key aspects of investigator turnover. First, they confirm that investigator turnover occurs, as more than half of respondents were truly “one-and-done.” Second, because a large proportion of respondents wanted to conduct more FDA-regulated trials but lacked opportunities to do so, mechanisms that match interested investigators with research sponsors are needed. Third, by focusing on the barriers we identified that affected investigators' decisions to no longer conduct FDA-regulated trials, future efforts to reduce investigator turnover can target issues that matter the most to investigators.

  18. Fuzzy barrier distributions

    International Nuclear Information System (INIS)

    Piasecki, E.

    2009-01-01

    Heavy-ion collisions often produce a fusion barrier distribution with structures displaying a fingerprint of couplings to highly collective excitations [1]. Basically the same distribution can be obtained from large-angle quasi-elastic scattering, though here the role of the many weak direct-reaction channels is unclear. For 2 0N e + 9 0Z r we have observed the barrier structures expected for the highly deformed neon projectile, but for 2 0N e + 9 2Z r we find completely smooth distribution (see Fig.1). We find that transfer channels in these systems are of similar strength but single particle excitations are significantly stronger in the latter case. They apparently reduce the 'resolving power' of the quasi-elastic channel, what leads to smeared out, or 'fuzzy' barrier distribution. This is the first case when such a phenomenon has been observed.(author)

  19. Barriers to evidence-based medicine: a systematic review.

    Science.gov (United States)

    Sadeghi-Bazargani, Homayoun; Tabrizi, Jafar Sadegh; Azami-Aghdash, Saber

    2014-12-01

    Evidence-based medicine (EBM) has emerged as an effective strategy to improve health care quality. The aim of this study was to systematically review and carry out an analysis on the barriers to EBM. Different database searching methods and also manual search were employed in this study using the search words ('evidence-based' or 'evidence-based medicine' or 'evidence-based practice' or 'evidence-based guidelines' or 'research utilization') and (barrier* or challenge or hinder) in the following databases: PubMed, Scopus, Web of Knowledge, Cochrane library, Pro Quest, Magiran, SID. Out of 2592 articles, 106 articles were finally identified for study. Research barriers, lack of resources, lack of time, inadequate skills, and inadequate access, lack of knowledge and financial barriers were found to be the most common barriers to EBM. Examples of these barriers were found in primary care, hospital/specialist care, rehabilitation care, medical education, management and decision making. The most common barriers to research utilization were research barriers, cooperation barriers and changing barriers. Lack of resources was the most common barrier to implementation of guidelines. The result of this study shows that there are many barriers to the implementation and use of EBM. Identifying barriers is just the first step to removing barriers to the use of EBM. Extra resources will be needed if these barriers are to be tackled. © 2014 John Wiley & Sons, Ltd.

  20. Market and Policy Barriers to Energy Storage Deployment

    Energy Technology Data Exchange (ETDEWEB)

    Bhatnagar, Dhruv [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Currier, Aileen [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hernandez, Jacquelynne [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ma, Ookie [Dept. of Energy (DOE), Washington DC (United States) Office of Energy Efficiency and Renewable Energy; Kirby, Brendan [Consultant

    2013-09-01

    Electric energy storage technologies can provide numerous grid services; there are a number of factors that restrict their current deployment. The most significant barrier to deployment is high capital costs, though several recent deployments indicate that capital costs are decreasing and energy storage may be the preferred economic alternative in certain situations. However, a number of other market and regulatory barriers persist, limiting further deployment. These barriers can be categorized into regulatory barriers, market (economic) barriers, utility and developer business model barriers, cross-cutting barriers and technology barriers.

  1. The diffusion of solar energy use in HK: What are the barriers?

    International Nuclear Information System (INIS)

    Zhang Xiaoling; Shen Liyin; Chan, Sum Yee

    2012-01-01

    The world is facing the severe challenges of energy depletion and carbon dioxide (CO 2 ) emissions, and solar energy is considered to be a promising source of renewable energy and effective solution. However, the application of solar energy is limited in practice due to various barriers. Based on data collected from a survey of practice, this paper identifies the key barriers to the deployment of solar photovoltaic (PV) energy systems in Hong Kong. These include “high initial and repair cost”, “long payback period”, “inadequate installation space and service infrastructure”, “lack of participation of stakeholders/community in energy policy” and “lack of incentives by legislation and regulation”. Recommendations for addressing these barriers are proposed. For example, the high cost of solar PV energy systems can be reduced by the development and mass production of low-cost fabrication technologies and high performance PV technologies. Solar thermal applications should be encouraged as they are much more economical than solar PVs. It is also recommended that the Hong Kong Government adopt strategies to encourage a greater use of solar energy systems. The results from this study not only provide useful information for the Government, the private sector and consumers in Hong Kong but are also likely to apply equally to other similar regions around the world. - Highlights: ► The Hong Kong Government needs to adopt various strategies to encourage the solar energy system application. ► This paper identifies the key barriers to the diffusion of solar energy systems from a questionnaire survey and case study in Hong Kong. ► The barriers highlighted from the questionnaire survey include “high initial and repair cost”, “long payback period”, “inadequate installation space and service infrastructure”, “lack of stakeholder/community participation in energy choices” and “legal and regulation constraints”.

  2. Recent advances in understanding/managing eosinophilic esophagitis in adults [v1; ref status: indexed, http://f1000r.es/5rn

    Directory of Open Access Journals (Sweden)

    David A. Katzka

    2015-08-01

    Full Text Available It is an exciting time for research in eosinophilic esophagitis (EoE. As a new and increasingly prevalent disease, it is receiving considerable attention in the medical world, resulting in a flood of new insights. Clearly, a genetic predisposition seems likely with the identification of abnormalities in thymic stromal lymphopoietin (TSLP, calpain14, and eotaxin-3 genes. There are also well-defined abnormalities described in esophageal epithelial barrier function in these patients. The relationship between gastroesophageal reflux disease (GERD and EoE remains unclear, but emerging data suggest that the concept of proton pump inhibitor responsive esophageal eosinophilia (PPIREE may retain less importance, as this subset of patients becomes a likely subset of EoE in general. Finally, we approach the looming issue of long-term maintenance therapy. Although we lack adequate specific data on how to provide long-term pharmacologic treatment, studies clearly show that for most patients, this is a progressive disease that warrants such consideration.

  3. Information barriers and authentication

    International Nuclear Information System (INIS)

    MacArthur, D.W.; Wolford, J.K.

    2001-01-01

    Acceptance of nuclear materials into a monitoring regime is complicated if the materials are in classified shapes or have classified composition. An attribute measurement system with an information barrier can be emplo,yed to generate an unclassified display from classified measurements. This information barrier must meet two criteria: (1) classified information cannot be released to the monitoring party, and (2) the monitoring party must be convinced that the unclassified output accurately represents the classified input. Criterion 1 is critical to the host country to protect the classified information. Criterion 2 is critical to the monitoring party and is often termed the 'authentication problem.' Thus, the necessity for authentication of a measurement system with an information barrier stems directly from the description of a useful information barrier. Authentication issues must be continually addressed during the entire development lifecycle of the measurement system as opposed to being applied only after the system is built.

  4. From a literature review to a multi-perspective framework for reverse logistics barriers and drivers

    DEFF Research Database (Denmark)

    Govindan, Kannan; Bouzon, Marina

    2018-01-01

    The emergence of stricter environmental regulations and the growing environmental consciousness of customers have forced industries to start thinking about environmental operations management with the help of reverse logistics application. In this process, influential factors such as drivers...... and barriers have to be examined, and stakeholders’ different perspectives on RL implementation and development should also be considered. This paper presents a multi-perspective framework for reverse logistics implementation using the lens of stakeholder theory. The multiple stakeholders’ perspective...... framework was developed based upon a structured literature review process. Fifty-four papers concerning these topical areas were thoroughly assessed and classified according to their structural dimensions and analytical categories. Two extensive lists of 37 drivers and 36 barriers, categorized and analyzed...

  5. Effects of Dietary Bacillus licheniformis on Gut Physical Barrier, Immunity, and Reproductive Hormones of Laying Hens.

    Science.gov (United States)

    Wang, Yang; Du, Wei; Lei, Kai; Wang, Baikui; Wang, Yuanyuan; Zhou, Yingshan; Li, Weifen

    2017-09-01

    Previous study showed that dietary Bacillus licheniformis (B. licheniformis) administration contributes to the improvement of laying performance and egg quality in laying hens. In this study, we aimed to further evaluate its underlying mechanisms. Three hundred sixty Hy-Line Variety W-36 hens (28 weeks of age) were randomized into four groups, each group with six replications (n = 15). The control group received the basal diet and the treatment groups received the same basal diets supplemented with 0.01, 0.03, and 0.06% B. licheniformis powder (2 × 10 10  cfu/g) for an 8-week trial. The results demonstrate that B. licheniformis significantly enhance the intestinal barrier functions via decreasing gut permeability, promoting mucin-2 transcription, and regulating inflammatory cytokines. The systemic immunity of layers in B. licheniformis treatment groups is improved through modulating the specific and non-specific immunity. In addition, gene expressions of hormone receptors, including estrogen receptor α, estrogen receptor β, and follicle-stimulating hormone receptor, are also regulated by B. licheniformis. Meanwhile, compared with the control, B. licheniformis significantly increase gonadotropin-releasing hormone level, but markedly reduce ghrelin and inhibin secretions. Overall, our data suggest that dietary inclusion of B. licheniformis can improve the intestinal barrier function and systemic immunity and regulate reproductive hormone secretions, which contribute to better laying performance and egg quality of hens.

  6. Fusion barrier characteristics of actinides

    Science.gov (United States)

    Manjunatha, H. C.; Sridhar, K. N.

    2018-03-01

    We have studied fusion barrier characteristics of actinide compound nuclei with atomic number range 89 ≤ Z ≤ 103 for all projectile target combinations. After the calculation of fusion barrier heights and positions, we have searched for their parameterization. We have achieved the empirical formula for fusion barrier heights (VB), positions (RB), curvature of the inverted parabola (ħω) of actinide compound nuclei with atomic number range 89 ≤ Z ≤ 103 for all projectile target combinations (6 projectile target combinations. The values produced by the present formula are also compared with experiments. The present pocket formula produces fusion barrier characteristics of actinides with the simple inputs of mass number (A) and atomic number (Z) of projectile-targets.

  7. Better Regulation and Public Procurement in Slovenian Municipalities

    Directory of Open Access Journals (Sweden)

    Maja KLUN

    2013-02-01

    Full Text Available The reduction of administrative burdens is a measure to improve regulatory quality. Most measures are directed towards reducing barriers for business while the issue of regulation inside government is not often posed. The research carried out in 2010 was intended to investigate how Slovenian municipalities and others in the public sector perceive measures to reduce administrative burdens and the areas in which they consider regulations to present the greatest burden. Results have shown that public procurement regulations are the greatest burden for municipalities and the public sector as a whole. Further research indicates which public procurement procedures municipalities used most often and what benefits they perceive in the amended legislation. Results indicate that most municipalities use open procedures most often, which procedurally is the most complex.

  8. Building energy efficiency for public hospitals and healthcare facilities in China: Barriers and drivers

    International Nuclear Information System (INIS)

    Wang, Tao; Li, Xiaodong; Liao, Pin-Chao; Fang, Dongping

    2016-01-01

    Maximizing energy efficiency within HHFs (hospitals and healthcare facilities) is a major challenge in the field of energy conservation. This paper studies the key barriers to the implementation of energy-efficient technologies in China's public HHFs. For this purpose, a preliminary survey was conducted at the Beijing Municipal Health Bureau in order to assess the energy conservation efforts being made at 20 public HHFs. In the survey, a list of specific barriers to energy efficiency was created and HHF staffs were asked to rank these barriers in the order of importance. The results show that the economic incentives, appropriate technology, as well as enforceable laws and regulations are insufficiently supported by the government, have become the most significant obstacles to the improvement of energy efficiency. To remedy this, policymakers should take a multipronged approach which addresses the hospitals, projects, and technical and operating procedures in order to encourage the full participation and support of all stakeholders involved. Specifically, the government should offer multilevel economic incentives and reward policies; establish practical mandatory targets for building energy efficiency; provide demonstrable best practices in terms of the project, techniques, and operating procedures; and promote awareness of the importance of property risk management. - Highlights: • We developed a checklist of building energy efficiency barriers of HHFs in China. • We took a survey to prioritize the barriers by the staff from 20 public HHFs. • Policy makers should provide multiple-level solutions to all the stakeholders. • Economic incentives, mandatory target, technique supports are critical drivers.

  9. Programmer's description of the Barrier Data Base

    International Nuclear Information System (INIS)

    Wall, D.W.; Jones, R.E.; Worrell, R.B.

    1976-12-01

    The Barrier Data Base is a body of information concerning different kinds of barriers that are used in safeguarding nuclear materials and installations. The two programs written for creating, updating, and manipulating the Barrier Data Base are discussed. The BARRIER program is used to add, delete, modify, display, or search for specific data in the data base. A utility program named NUMBER is used to compress and renumber the barrier and threat tables

  10. Permanent isolation surface barrier development plan

    International Nuclear Information System (INIS)

    Wing, N.R.

    1994-01-01

    The exhumation and treatment of wastes may not always be the preferred alternative in the remediation of a waste site. In-place disposal alternatives, under certain circumstances, may be the most desirable alternatives to use in the protection of human health and the environment. The implementation of an in-place disposal alternative will likely require some type of protective covering that will provide long-term isolation of the wastes from the accessible environment. Even if the wastes are exhumed and treated, a long-term barrier may still be needed to adequately dispose of the treated wastes or any remaining waste residuals. Currently, no open-quotes provenclose quotes long-term barrier is available. The Hanford Site Permanent Isolation Surface Barrier Development Program (BDP) was organized to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site. The permanent isolation barrier technology also could be used at other sites. Permanent isolation barriers use engineered layers of natural materials to create an integrated structure with redundant protective features. Drawings of conceptual permanent isolation surface barriers are shown. The natural construction materials (e.g., fine soil, sand, gravel, riprap, asphalt) have been selected to optimize barrier performance and longevity. The objective of current designs is to use natural materials to develop a maintenance-free permanent isolation surface barrier that isolates wastes for a minimum of 1,000 years by limiting water drainage to near-zero amounts; reducing the likelihood of plant, animal, and human intrusion; controlling the exhalation of noxious gases; and minimizing erosion-related problems

  11. Permanent isolation surface barrier development plan

    Energy Technology Data Exchange (ETDEWEB)

    Wing, N.R.

    1994-01-01

    The exhumation and treatment of wastes may not always be the preferred alternative in the remediation of a waste site. In-place disposal alternatives, under certain circumstances, may be the most desirable alternatives to use in the protection of human health and the environment. The implementation of an in-place disposal alternative will likely require some type of protective covering that will provide long-term isolation of the wastes from the accessible environment. Even if the wastes are exhumed and treated, a long-term barrier may still be needed to adequately dispose of the treated wastes or any remaining waste residuals. Currently, no {open_quotes}proven{close_quotes} long-term barrier is available. The Hanford Site Permanent Isolation Surface Barrier Development Program (BDP) was organized to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site. The permanent isolation barrier technology also could be used at other sites. Permanent isolation barriers use engineered layers of natural materials to create an integrated structure with redundant protective features. Drawings of conceptual permanent isolation surface barriers are shown. The natural construction materials (e.g., fine soil, sand, gravel, riprap, asphalt) have been selected to optimize barrier performance and longevity. The objective of current designs is to use natural materials to develop a maintenance-free permanent isolation surface barrier that isolates wastes for a minimum of 1,000 years by limiting water drainage to near-zero amounts; reducing the likelihood of plant, animal, and human intrusion; controlling the exhalation of noxious gases; and minimizing erosion-related problems.

  12. Tunnelling through a Gaussian random barrier

    International Nuclear Information System (INIS)

    Bezak, Viktor

    2008-01-01

    A thorough analysis of the tunnelling of electrons through a laterally inhomogeneous rectangular barrier is presented. The barrier height is defined as a statistically homogeneous Gaussian random function. In order to simplify calculations, we assume that the electron energy is low enough in comparison with the mean value of the barrier height. The randomness of the barrier height is defined vertically by a constant variance and horizontally by a finite correlation length. We present detailed calculations of the angular probability density for the tunnelled electrons (i.e. for the scattering forwards). The tunnelling manifests a remarkably diffusive character if the wavelength of the electrons is comparable with the correlation length of the barrier

  13. Prototype Hanford Surface Barrier: Design basis document

    International Nuclear Information System (INIS)

    Myers, D.R.; Duranceau, D.A.

    1994-11-01

    The Hanford Site Surface Barrier Development Program (BDP) was organized in 1985 to develop the technology needed to provide a long-term surface barrier capability for the Hanford Site and other arid sites. This document provides the basis of the prototype barrier. Engineers and scientists have momentarily frozen evolving barrier designs and incorporated the latest findings from BDP tasks. The design and construction of the prototype barrier has required that all of the various components of the barrier be brought together into an integrated system. This integration is particularly important because some of the components of the protective barreir have been developed independently of other barreir components. This document serves as the baseline by which future modifications or other barrier designs can be compared. Also, this document contains the minutes of meeting convened during the definitive design process in which critical decisions affecting the prototype barrier's design were made and the construction drawings

  14. Personal Space Regulation in Williams Syndrome: The Effect of Familiarity

    Science.gov (United States)

    Lough, Emma; Flynn, Emma; Riby, Deborah M.

    2016-01-01

    Personal space refers to a protective barrier that we strive to maintain around our body. We examined personal space regulation in young people with Williams syndrome (WS) and their typically developing, chronological age-matched peers using a parent report questionnaire and a stop-distance paradigm. Individuals with WS were reported by their…

  15. Market barriers to welfare product innovations

    NARCIS (Netherlands)

    Binnekamp, M.H.A.; Ingenbleek, P.T.M.

    2006-01-01

    New products that are based on higher animal welfare standards encounter several barriers on the road to market acceptance. The authors focus on the Dutch poultry sector and distinguish between retailer and consumer barriers. Retailer barriers include the powerful position of retailers, the price

  16. Cancer symptom awareness and barriers to medical help seeking in Scottish adolescents: a cross-sectional study.

    Science.gov (United States)

    Hubbard, Gill; Macmillan, Iona; Canny, Anne; Forbat, Liz; Neal, Richard D; O'Carroll, Ronan E; Haw, Sally; Kyle, Richard G

    2014-10-29

    Initiatives to promote early diagnosis include raising public awareness of signs and symptoms of cancer and addressing barriers to seeking medical help about cancer. Awareness of signs and symptoms of cancer and emotional barriers, such as fear, worry, and embarrassment, strongly influence help seeking behaviour. Whether anxiety influences seeking medical help about cancer is not known. The purpose of this study about adolescents was to examine: 1) the relationship between contextual factors and awareness of signs and symptoms of cancer and barriers (including emotional barriers) to seeking medical help, and 2) associations between anxiety and endorsed barriers to seeking medical help. Interpretation of data is informed by the common sense model of the self-regulation of health and illness. A cross-sectional study of 2,173 Scottish adolescents (age 12/13 years) using the Cancer Awareness Measure. Socio-demographic questions were also included. Descriptive statistics were calculated and two Poisson regression models were built to determine independent predictors of: 1) the number of cancer warning signs recognized, and; 2) number of barriers to help seeking endorsed. Analysis identified that knowing someone with cancer was a significant independent predictor of recognising more cancer warning signs whereas Black and Minority Ethnic status was a significant independent predictor of recognising fewer cancer warning signs. Emotional barriers were the most commonly endorsed, followed by family, service and practical barriers. Over two thirds of adolescents were 'worried about what the doctor would find' and over half were 'scared'. Higher anxiety scores, knowing more cancer warning signs and female gender were significant independent predictors of barriers to help seeking. Improving cancer awareness and help seeking behaviour during adolescence may contribute to early presentation. Contextual factors (for example, ethnicity, gender, knowing someone with cancer), and

  17. Deployment Efficiency and Barrier Effectiveness Testing of a Temporary Anti-Personnel (TAP) Barrier System.

    Energy Technology Data Exchange (ETDEWEB)

    Allen, David James [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hedrick, Charles D. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Martinez, Ruben [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-02-01

    This report documents tests conducted by Sandia National Laboratories (SNL) on behalf of the U.S. Department of State to evaluate a temporary anti-personnel (TAP) barrier system developed by Mitigation Technologies. For this, the SNL Denial and Structural Assessment department developed a test protocol for the evaluation of the TAP barrier system on the basis of deployment efficiency and barrier effectiveness against a riotous/mob attack threat. The test protocol was then executed by SNL personnel and the results of the testing are documented.

  18. Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

    Science.gov (United States)

    Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R

    2015-06-01

    In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an

  19. Effects of barrier composition and electroplating chemistry on adhesion and voiding in copper/dielectric diffusion barrier films

    Energy Technology Data Exchange (ETDEWEB)

    Birringer, Ryan P.; Dauskardt, Reinhold H. [Department of Materials Science and Engineering, Stanford University, Durand Building, Stanford, California 94305-4034 (United States); Shaviv, Roey [Novellus Systems Inc., 4000 North First Street, San Jose, California 95134 (United States); Geiss, Roy H.; Read, David T. [National Institute of Standards and Technology, 325 Broadway, Boulder, Colorado 80305 (United States)

    2011-08-15

    The effects of electroplating chemistry and dielectric diffusion barrier composition on copper voiding and barrier adhesion are reported. Adhesion was quantified using the four-point bend thin film adhesion technique, and voiding in the Cu films was quantified using scanning electron microscopy. A total of 12 different film stacks were investigated, including three different Cu electroplating chemistries and four different barrier materials (SiN, N-doped SiC, O-doped SiC, and dual-layer SiC). Both plating chemistry and barrier composition have a large effect on interface adhesion and voiding in the Cu film. X-ray photoelectron spectroscopy was used to investigate the segregation of Cu electroplating impurities, such as S and Cl, to the Cu/barrier interface. Secondary ion mass spectrometry was used to quantify oxygen content at the Cu/barrier interface in a subset of samples. This interface oxygen content is correlated with measured adhesion values.

  20. Measuring solvent barrier properties of paper

    International Nuclear Information System (INIS)

    Bollström, Roger; Saarinen, Jarkko J; Toivakka, Martti; Räty, Jukka

    2012-01-01

    New methods for measuring barrier properties against solvents, acids and bases on dispersion coated paper were developed and investigated. Usability, reliability and repeatability were compared both between the new methods and with the standardized method for measuring barrier properties against water vapor. Barrier properties could be measured with all methods and the results obtained by the different methods were in correlation with each other. A qualitative method based on a trace color provided an indicative result, whereas further developed methods also took into account the durability. The effective barrier lifetime could be measured by measuring the conductivity through the substrate as a function of time, or by utilizing a glass prism where the change in refractive index caused by penetrated liquid was monitored, also as a function of time. Barrier properties against water and humidity were also measured and were found not to be predictors for barrier properties against either solvents, or acids or bases, which supports the need to develop new methods

  1. Practical and social barriers to switching from lead to non-toxic gunshot

    DEFF Research Database (Denmark)

    Kanstrup, Niels

    2015-01-01

    without jeopardising the hunters’ interests and weakening the hunters’ community. On the contrary, it is believed, though never investigated, that the public image value of hunting not being connected to a pollutant such as lead is of paramount importance for the perception and long-term political...... targeted at sea ducks. In Denmark, the use of lead shot was first regulated in 1985 by setting up a ban on inter alia the use of lead shot for hunting in 26 wetlands designated as Ramsar-sites and for clay pigeon shooting in certain areas. Denmark enforced a total ban on the use of lead shot in 1993 in all...... areas outside forests and with a subsequent enforcement of a lead shot ban in forests in 1996. Since then all use, trade and possession of lead shot has been banned throughout the country (Kanstrup 2006). The phase-out of lead shot raised a number of practical and social barriers. The first barrier...

  2. Barriers to the adoption of energy-saving technologies in the building sector: A survey study of Jing-jin-tang, China

    International Nuclear Information System (INIS)

    Du, Ping; Zheng, Li-Qun; Xie, Bai-Chen; Mahalingam, Arjun

    2014-01-01

    The building sector of China currently consumes 20% of the total energy consumption. Studies on barriers to the adoption of building energy-saving technologies are of great significance on implementing policies related to achieving energy-saving goals. This paper studied 15 barriers with the aid of information collected through questionnaires and semi-structured interviews. The respondents were 135 employees working in the Jing-jin-tang area. Based on the results of the factor analysis, the barriers were categorized into five groups: attitudes of stakeholders, policies and regulations, auxiliary resources, profitability, and adaptability of the technologies. Analysis of the entire sample showed that the stakeholders’ reluctance to use was the largest barrier, followed by high initial investment and low profitability. Further analysis showed that the occupation and designation of the respondents and the size of the enterprises that they served influenced their perspectives on the barriers. It was found that architects attributed more importance to the adoption of energy-saving technologies than contractors; barriers confronted by employees of large enterprises and small enterprises were different; managers perceived weaker barriers than frontline employees and were more optimistic about the prospect of building energy-saving technologies. Finally, policy recommendations were proposed based on these in-depth and targeted analyses. - Highlights: • Fifteen barriers to the adoption of energy-saving technologies are discussed. • Surveys are conducted in one of China's most technologically developed area. • The barriers are divided into 5 groups according to the results of factor analysis. • Barriers related to profitability greatly hamper the adoption of the technologies. • Comparative analyses show the background of respondents influence their viewpoints

  3. Radon barrier: Method of testing airtightness

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn; Buch-Hansen, Thomas Cornelius

    2017-01-01

    The test method NBI 167/02 Radon membrane: Test of airtightness can be used for determining the airtightness of a radon barrier as a system solution. The test determines the air infiltration through the radon barrier for a number of levels of air pressure differences. The airflow through versus...... of the barrier with the low air pressure, through a well-defined opening, as a modification of the test method in general. Results, obtained using the improved test method, are shown for a number of radon barriers tested....

  4. A transgenic zebrafish model for the in vivo study of the blood and choroid plexus brain barriers using claudin 5

    Directory of Open Access Journals (Sweden)

    Lisanne Martine van Leeuwen

    2018-02-01

    Full Text Available The central nervous system (CNS has specific barriers that protect the brain from potential threats and tightly regulate molecular transport. Despite the critical functions of the CNS barriers, the mechanisms underlying their development and function are not well understood, and there are very limited experimental models for their study. Claudin 5 is a tight junction protein required for blood brain barrier (BBB and, probably, choroid plexus (CP structure and function in vertebrates. Here, we show that the gene claudin 5a is the zebrafish orthologue with high fidelity expression, in the BBB and CP barriers, that demonstrates the conservation of the BBB and CP between humans and zebrafish. Expression of claudin 5a correlates with developmental tightening of the BBB and is restricted to a subset of the brain vasculature clearly delineating the BBB. We show that claudin 5a-expressing cells of the CP are ciliated ependymal cells that drive fluid flow in the brain ventricles. Finally, we find that CP development precedes BBB development and that claudin 5a expression occurs simultaneously with angiogenesis. Thus, our novel transgenic zebrafish represents an ideal model to study CNS barrier development and function, critical in understanding the mechanisms underlying CNS barrier function in health and disease.

  5. Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases.

    Science.gov (United States)

    González, Hugo; Elgueta, Daniela; Montoya, Andro; Pacheco, Rodrigo

    2014-09-15

    Neuroinflammation constitutes a fundamental process involved in the progression of several neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis and multiple sclerosis. Microglial cells play a central role in neuroinflammation, promoting neuroprotective or neurotoxic microenvironments, thus controlling neuronal fate. Acquisition of different microglial functions is regulated by intercellular interactions with neurons, astrocytes, the blood-brain barrier, and T-cells infiltrating the central nervous system. In this study, an overview of the regulation of microglial function mediated by different intercellular communications is summarised and discussed. Afterward, we focus in T-cell-mediated regulation of neuroinflammation involved in neurodegenerative disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Hataedock treatment has preventive therapeutic effects for atopic dermatitis through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice.

    Science.gov (United States)

    Cha, Ho-Yeol; Ahn, Sang-Hyun; Cheon, Jin-Hong; Park, Sun-Young; Kim, Kibong

    2017-07-12

    Hataedock treatment is traditionally used for the purpose of preventing the future skin disease by feeding herbal extracts to the newborn in traditional Chinese and Korean medicine. This study investigated the preventive therapeutic effects of Hataedock (HTD) treatment for atopic dermatitis (AD) through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice. To the HTD treatment group, the extract of Coptis japonica Makino and Glycyrrhiza uralensis Fischer, which analyzed with High Performance Liquid Chromatography (HPLC)-fingerprint for quality consistency, was administered orally to the 3-week-old mice before inducing AD. After that, Dermatophagoides farinae was applied except the control group to induce AD-like skin lesions. We confirmed the effects of HTD on morphological changes, protection of skin barrier, regulation of Th2 differentiation, inflammation regulation and induction of apoptosis through histochemistry, immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. HTD effectively reduced edema, angiogenesis and skin lesion. HTD also increased the levels of liver X receptor (LXR) and filaggrin but decreased the level of protein kinase C (PKC) (pprotection of skin barrier. Therefore, HTD may have potential applications for alternative and preventive treatment in the management of AD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Effect of Acer tegmentosum bark on atopic dermatitis-like skin lesions in NC/Nga mice.

    Science.gov (United States)

    Yang, Gabsik; An, Duckgun; Lee, Mi-Hwa; Lee, Kyungjin; Kim, Bumjung; Suman, Chinannai Khanita; Ham, Inhye; Choi, Ho-Young

    2016-01-11

    Atopic dermatitis (AD) is a chronic and relapsing inflammatory condition characterized by pruritic and eczematous skin lesions that requires safe and effective pharmacological therapy. The bark of Acer tegmentosum Maxim trees has been used in Korean folk and traditional medicine to treat abscesses, surgical bleeding, liver diseases, and AD. To investigate the therapeutic effect of A. tegmentosum, on a mouse model of Dermatophagoides farinae (Df)-induced AD. Development of AD-like skin lesions was induced by repetitive skin contact with barrier-disrupted backs of NC/Nga mice with Df body ointment, and the effects of A. tegmentosum were evaluated on the basis of histopathological skin assessment results, ear swelling, and cytokine production in the dorsal skin. The component of A. tegmentosum, salidroside, inhibited the production of TSLP in KCMH-1 cells, which indicated that its production could be pharmacologically regulated. Topical application of A. tegmentosum for 1 week after Df body ointment challenge significantly reduced ear swelling and improved dorsal skin lesions. Suppression of dermatitis by combined therapy was accompanied by a decrease in the skin level of Th2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13, plasma levels of thymus and activation-regulated chemokine, and IgE. Induction of thymic stromal lymphopoietin, which leads to a systemic Th2 response, was also reduced in in vivo and in vitro by A. tegmentosum and salidroside. Our findings suggest that A. tegmentosum treatment has a significant therapeutic effect on Df-induced AD-like skin lesions on NC/Nga mice through inhibition of thymic stromal lymphopoietin and IgE via a mechanism that may inhibit Th2-mediated immune responses. These results suggest that A. tegmentosum and salidroside may be useful tools for the treatment of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Groundwater governance in Asia: present state and barriers to implementation of good governance

    Science.gov (United States)

    Tanaka, T.

    2014-09-01

    The present state of groundwater governance in Asia was reviewed. The main problem regarding groundwater resources in each Asian country is overexploitation, causing water level decline, land subsidence and salt water intrusion. For those groundwater hazards, many countries have established regulations such as laws and regulations as countermeasures. However, those laws and regulations are not the basic laws on groundwater resources, but only for countermeasures to prevent groundwater hazards. Common problems and barriers for implementing groundwater governance in Asian countries are that there is more than one institute with different and sometimes overlapping responsibilities in groundwater management. To overcome those conflicts among institutions and establishment of good governance, it is necessary to establish an agency in the government as one coordinate function reinforcing the direct coordination and facilitation of groundwater policy-making and management. As one such framework, the conceptual law called the Water Cycle Basic Law, which is under planning in Japan, is examined in this paper.

  9. Double barrier system for an in situ conversion process

    Science.gov (United States)

    McKinzie, Billy John [Houston, TX; Vinegar, Harold J [Bellaire, TX; Cowan, Kenneth Michael [Sugar land, TX; Deeg, Wolfgang Friedrich Johann [Houston, TX; Wong, Sau-Wai [Rijswijk, NL

    2009-05-05

    A barrier system for a subsurface treatment area is described. The barrier system includes a first barrier formed around at least a portion of the subsurface treatment area. The first barrier is configured to inhibit fluid from exiting or entering the subsurface treatment area. A second barrier is formed around at least a portion of the first barrier. A separation space exists between the first barrier and the second barrier.

  10. Engineered barriers: current status 1989

    International Nuclear Information System (INIS)

    Atkinson, A.; Marsh, G.B.

    1989-06-01

    This report summarises the current state of research relevant to assessing the performance of engineered barriers made of steel and concrete in radioactive waste repositories. The objective of these barriers is to contain substantially the radionuclides within them by providing both physical and chemical impediment to their release. The physical barriers are of most value for highly soluble isotopes with relatively short half-lives (eg 137 Cs), since they can provide a measure of containment until a large fraction of the activity has decayed. In addition they can facilitate retrievability for some period after disposal. The chemical barriers operate by beneficial conditioning of the near field groundwater and providing sites for sorption of radionuclides. Both of these reduce the aqueous concentration of radionuclides in the near field. (author)

  11. Transport barrier in Helical system

    International Nuclear Information System (INIS)

    Ida, Katsumi

    1998-01-01

    Experiments on the transport barrier in Helical plasmas are reviewed. There are two mechanisms of transport improvement, that results in the formation of the transport barrier. One is the improvement of neoclassical transport by reducing the ripple loss with radial electric field, which exist only in helical plasma. The other is the improvement of anomalous transport due to the suppression of fluctuations associated with a radial electric field shear both in tokamak and helical plasma. The formation of the transport barrier can be triggered by the radial electric field shear associated with the transition of the radial electric field (L/H transition or ion-electron root transition) or the peaked density or the optimization of magnetic field shear. The mechanisms of transport barrier formation are also discussed. (author). 60 refs

  12. Propitious Therapeutic Modulators to Prevent Blood-Spinal Cord Barrier Disruption in Spinal Cord Injury.

    Science.gov (United States)

    Kumar, Hemant; Ropper, Alexander E; Lee, Soo-Hong; Han, Inbo

    2017-07-01

    The blood-spinal cord barrier (BSCB) is a specialized protective barrier that regulates the movement of molecules between blood vessels and the spinal cord parenchyma. Analogous to the blood-brain barrier (BBB), the BSCB plays a crucial role in maintaining the homeostasis and internal environmental stability of the central nervous system (CNS). After spinal cord injury (SCI), BSCB disruption leads to inflammatory cell invasion such as neutrophils and macrophages, contributing to permanent neurological disability. In this review, we focus on the major proteins mediating the BSCB disruption or BSCB repair after SCI. This review is composed of three parts. Section 1. SCI and the BSCB of the review describes critical events involved in the pathophysiology of SCI and their correlation with BSCB integrity/disruption. Section 2. Major proteins involved in BSCB disruption in SCI focuses on the actions of matrix metalloproteinases (MMPs), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), angiopoietins (Angs), bradykinin, nitric oxide (NO), and endothelins (ETs) in BSCB disruption and repair. Section 3. Therapeutic approaches discusses the major therapeutic compounds utilized to date for the prevention of BSCB disruption in animal model of SCI through modulation of several proteins.

  13. Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

    Science.gov (United States)

    Boita, Monica; Heffler, Enrico; Omedè, Paola; Bellocchia, Michela; Bussolino, Claudia; Solidoro, Paolo; Giorgis, Veronica; Guerrera, Francesco; Riva, Giuseppe; Brussino, Luisa; Bucca, Caterina; Rolla, Giovanni

    2018-01-01

    Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity. © 2018 S. Karger AG, Basel.

  14. Activated human nasal epithelial cells modulate specific antibody response against bacterial or viral antigens.

    Directory of Open Access Journals (Sweden)

    Chiou-Yueh Yeh

    Full Text Available Nasal mucosa is an immune responsive organ evidenced by eliciting both specific local secretory IgA and systemic IgG antibody responses with intra-nasal administration of antigens. Nevertheless, the role of nasal epithelial cells in modulating such responses is unclear. Human nasal epithelial cells (hNECs obtained from sinus mucosa of patients with chronic rhinosinusitis were cultured in vitro and firstly were stimulated by Lactococcus lactis bacterium-like particles (BLPs in order to examine their role on antibody production. Secondly, both antigens of immunodominant protein IDG60 from oral Streptococcus mutans and hemagglutinin (HA from influenza virus were tested to evaluate the specific antibody response. Stimulated hNECs by BLPs exhibited a significant increase in the production of interleukin-6 (IL-6, and thymic stromal lymphopoietin (TSLP. Conditioned medium of stimulated hNECs has effects on enhancing the proliferation of CD4+ T cells together with interferon-γ and IL-5 production, increasing the costimulatory molecules on dendritic cells and augmenting the production of IDG60 specific IgA, HA specific IgG, IgA by human peripheral blood lymphocytes. Such production of antigen specific IgG and IgA is significantly counteracted in the presence of IL-6 and TSLP neutralizing antibodies. In conclusion, properly stimulated hNECs may impart immuno-modulatory effects on the antigen-specific antibody response at least through the production of IL-6 and TSLP.

  15. Mediated Intercultural Communication Barrier in No Drama Zone! Group

    OpenAIRE

    Lizal, Valentino

    2015-01-01

    This research study aimed to describe the mediated intercultural communication barriers in the No Drama Zone! group. This study is a qualitative descriptive type of research, with case study method. By doing in depth interview and observation, researcher found two barriers that generates other barriers in the group's mediated intercultural communication. The two big barriers were: language and physical barriers. Language barriers in this group generated two barriers, emotional barrier and pe...

  16. Barriers to the widespread adoption of health data standards: an exploratory qualitative study in tertiary healthcare organizations in Saudi Arabia.

    Science.gov (United States)

    Alkraiji, Abdullah; Jackson, Thomas; Murray, Ian

    2013-04-01

    Although health data standards are perceived to be the essential solution for interoperability barriers within medical IT systems, the level of adoption of those standards still remains frustratingly low. Little is known about the barriers facing their adoption within the healthcare organizations context. In addressing this gap in the literature, based on IT related standards adoption theories such as Diffusion of Innovation Theory and the theories surrounding the Economics of Standards, a qualitative multiple-case study was undertaken in Saudi Arabia to investigate those barriers. The results exposed that few standards were adopted because of four broad reasons, managerial, technical, educational and governmental. While some of the findings can be rooted to those related standards theories, others can be underpinned through the normative literature. Core barriers are the lack of a national regulator and a data exchange plan, and the lack of an adequate policy regarding medical IT systems and information management and national healthcare system; also important are technical barriers and the switching costs to the standards. The outcome of this study can be used in forming effective interventions when planning to use health data standards and, in particular those in developing countries.

  17. A Septin-Dependent Diffusion Barrier at Dendritic Spine Necks.

    Directory of Open Access Journals (Sweden)

    Helge Ewers

    Full Text Available Excitatory glutamatergic synapses at dendritic spines exchange and modulate their receptor content via lateral membrane diffusion. Several studies have shown that the thin spine neck impedes the access of membrane and solute molecules to the spine head. However, it is unclear whether the spine neck geometry alone restricts access to dendritic spines or if a physical barrier to the diffusion of molecules exists. Here, we investigated whether a complex of septin cytoskeletal GTPases localized at the base of the spine neck regulates diffusion across the spine neck. We found that, during development, a marker of the septin complex, Septin7 (Sept7, becomes localized to the spine neck where it forms a stable structure underneath the plasma membrane. We show that diffusion of receptors and bulk membrane, but not cytoplasmic proteins, is slower in spines bearing Sept7 at their neck. Finally, when Sept7 expression was suppressed by RNA interference, membrane molecules explored larger membrane areas. Our findings indicate that Sept7 regulates membrane protein access to spines.

  18. Tax regulating carbon market in Brazil: barriers and perspectives

    International Nuclear Information System (INIS)

    Marques, Fernando; Magalhaes, Gerusa; Parente, Virginia

    2010-01-01

    The world is moving towards a low carbon economy to fight global warming caused by increases in anthropogenic emissions of greenhouse gases (GHGs). The carbon market beckons as a promising opportunity for Brazil through Clean Development Mechanism (CDM) projects, which result in Certified Emission Reductions (CERs). Although Brazil is responsible for about 8% of all CDM projects in the world, there is still no specific tax regulation for CERs, thus hindering the development of carbon market in Brazil. It is essential that Brazil have a consistent internal framework which guarantees to potential investors a minimum security on the legal and fiscal operations of CERs. There are government institutions, considering the current law and that, given the number of bills being processed in Congress, are not definitive. Such bills have different understandings for the legal classification of CERs and the related tax treatment. This article supports an urgent need for a regulatory tax system for CERs, proposing a tax exemption on transactions involving CERs in order to encourage the effective development of carbon markets in Brazil in the context of the currently international legal system in which Kyoto Protocol is based. (author)

  19. Review of the Current State of UAV Regulations

    Directory of Open Access Journals (Sweden)

    Claudia Stöcker

    2017-05-01

    Full Text Available UAVs—unmanned aerial vehicles—facilitate data acquisition at temporal and spatial scales that still remain unachievable for traditional remote sensing platforms. However, current legal frameworks that regulate UAVs present significant barriers to research and development. To highlight the importance, impact, and diversity of UAV regulations, this paper provides an exploratory investigation of UAV regulations on the global scale. For this, the methodological approach consists of a research synthesis of UAV regulations, including a thorough literature review and a comparative analysis of national regulatory frameworks. Similarities and contrasting elements in the various national UAV regulations are explored including their statuses from the perspectives of past, present, and future trends. Since the early 2000s, countries have gradually established national legal frameworks. Although all UAV regulations have one common goal—minimizing the risks to other airspace users and to both people and property on the ground—the results reveal distinct variations in all the compared variables. Furthermore, besides the clear presence of legal frameworks, market forces such as industry design standards and reliable information about UAVs as public goods are expected to shape future developments.

  20. Transportation Energy Futures Series. Non-Cost Barriers to Consumer Adoption of New Light-Duty Vehicle Technologies

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, Thomas [Argonne National Lab. (ANL), Argonne, IL (United States)

    2013-03-01

    Consumer preferences are key to the adoption of new vehicle technologies. Barriers to consumer adoption include price and other obstacles, such as limited driving range and charging infrastructure; unfamiliarity with the technology and uncertainty about direct benefits; limited makes and models with the technology; reputation or perception of the technology; standardization issues; and regulations. For each of these non-cost barriers, this report estimates an effective cost and summarizes underlying influences on consumer preferences, approximate magnitude and relative severity, and assesses potential actions, based on a comprehensive literature review. While the report concludes that non-cost barriers are significant, effective cost and potential market share are very uncertain. Policies and programs including opportunities for drivers to test drive advanced vehicles, general public outreach and information programs, incentives for providing charging and fueling infrastructure, and development of technology standards were examined for their ability to address barriers, but little quantitative data exists on the effectiveness of these measures. This is one in a series of reports produced as a result of the Transportation Energy Futures project, a Department of Energy-sponsored multi-agency effort to pinpoint underexplored strategies for reducing GHGs and petroleum dependence related to transportation. View all reports on the TEF Web page, http://www.eere.energy.gov/analysis/transportationenergyfutures/index.html.

  1. SOR/83-77, Physical Security Regulations

    International Nuclear Information System (INIS)

    1983-01-01

    These Regulations establish and require the maintenance of security systems, equipment and procedures to implement Canada's international obligations regarding security at those nuclear facilities. The Regulations, which determine the different areas in a nuclear facility, provide for the establishment of security barriers around the ''protected areas'' occupied by facilities and prescribe that the licensees (operators) are required to keep the facilities for which they hold a licence under constant surveillance. They must also make arrangements for a response force - a local, provincial or federal police force detachment or similar force - to provide assistance where necessary. No person may enter a protected area without written authorization from the licensee concerned. Inspectors appointed under the Atomic Energy Control Regulations or designated under an agreement between Canada and the IAEA may be granted an authorization to enter such areas to discharge their duties. The Regulations have been amended by SOR/84-81 of 12 January 1988 to add certain requirements concerning documentary evidence and the duties of the board; by SOR/85-1016 of 25 October 1985 to revise the definition of response force and provide other clarifications; by SOR/91-585 of 10 October 1991 to clarify wording in French. (NEA)

  2. Article Including Environmental Barrier Coating System

    Science.gov (United States)

    Lee, Kang N. (Inventor)

    2015-01-01

    An enhanced environmental barrier coating for a silicon containing substrate. The enhanced barrier coating may include a bond coat doped with at least one of an alkali metal oxide and an alkali earth metal oxide. The enhanced barrier coating may include a composite mullite bond coat including BSAS and another distinct second phase oxide applied over said surface.

  3. Psychological Barriers to Behavior Change: How to indentify the barriers that inhibit change

    OpenAIRE

    Olson, James M.

    1992-01-01

    Adopting a healthy lifestyle often requires changing patterns of behavior. This article describes three categories of psychological barriers to behavior change: those that prevent the admission of a problem, those that interfere with initial attempts to change behavior, and those that make long-term change difficult. Strategies are identified that family physicians can use to overcome the barriers.

  4. Rare disease research: Breaking the privacy barrier

    Directory of Open Access Journals (Sweden)

    Deborah Mascalzoni

    2014-06-01

    Full Text Available Due to the few patients affected, rare disease research has to count on international registries to exist in order to produce significant research outputs. Data sharing of registries is therefore a unique resource to allow rare disease research to flourish and any lost data will jeopardize the quality of an already extremely difficult research. The rules usually applied to research such as the right to withdraw or the need for specific consent for every use of data can be detrimental in order to get effective results. Privacy rights regulated through traditional informed consent mechanisms have been regarded as a major barrier in order to effectively share data worldwide. Some authors argue that this barrier hampers results that could be beneficial to the patients so that another right will be overstated: the right to quality healthcare. We argue in this paper that privacy has been often interpreted just one-sided as the right to secrecy but it can entail another meaning: the right to manage one's own private sphere. Managing it pertains, not only to the right to deny access, but also to the right to grant access. At the same time research on patient participation and transparency shows that new forms of IT-based informed consent can provide a good balance between the right of individuals to be in control of their data and the opportunity for science to pursue international research.

  5. Electrical characteristics of schottky barriers on 4H-SiC: The effects of barrier height nonuniformity

    Science.gov (United States)

    Skromme, B. J.; Luckowski, E.; Moore, K.; Bhatnagar, M.; Weitzel, C. E.; Gehoski, T.; Ganser, D.

    2000-03-01

    Electrical properties, including current-voltage (I-V) and capacitance-voltage (C-V) characteristics, have been measured on a large number of Ti, Ni, and Pt-based Schottky barrier diodes on 4H-SiC epilayers. Various nonideal behaviors are frequently observed, including ideality factors greater than one, anomalously low I-V barrier heights, and excess leakage currents at low forward bias and in reverse bias. The nonidealities are highly nonuniform across individual wafers and from wafer to wafer. We find a pronounced linear correlation between I-V barrier height and ideality factor for each metal, while C-V barrier heights remain constant. Electron beam induced current (EBIC) imaging strongly suggests that the nonidealities result from localized low barrier height patches. These patches are related to discrete crystal defects, which become visible as recombination centers in the EBIC images. Alternative explanations involving generation-recombination current, uniform interfacial layers, and effects related to the periphery are ruled out.

  6. E. coli O124 K72 alters the intestinal barrier and the tight junctions proteins of guinea pig intestine.

    Science.gov (United States)

    Ren, Xiaomeng; Zhu, Yanyan; Gamallat, Yaser; Ma, Shenhao; Chiwala, Gift; Meyiah, Abdo; Xin, Yi

    2017-10-01

    Our research group previously isolated and identified a strain of pathogenic Escherichia coli from clinical samples called E. coli O124 K72. The present study was aimed at determining the potential effects of E. coli O124 K72 on intestinal barrier functions and structural proteins integrity in guinea pig. Guinea pigs were grouped into three groups; control (CG); E. coli O124 K72 (E. coli); and probiotics Lactobacillus rhamnosus (LGG). Initially, we create intestinal dysbiosis by giving all animals Levofloxacin for 10days, but the control group (CG) received the same volume of saline. Then, the animals received either E. coli O124 K72 (E. coli) or Lactobacillus rhamnosus (LGG) according to their assigned group. E. coli O124 K72 treatment significantly affected colon morphology and distorted intestinal barrier function by up-regulating Claudin2 and down-regulating Occludin. In addition, E. coli upregulated the mRNA expression of MUC1, MUC2, MUC13 and MUC15. Furthermore, suspected tumor was found in the E. coli treated animals. Our results suggested that E. coli O124 K72 strain has adverse effects on intestinal barrier functions and is capable of altering integrity of structural proteins in guinea pig model while at same time it may have a role in colon carcinogenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Air barrier systems: Construction applications

    Energy Technology Data Exchange (ETDEWEB)

    Perrault, J.C

    1989-01-01

    An examination is presented of how ordinary building materials can be used in an innovative manner to design, detail, and construct effective air barrier systems for common types of walls. For residential construction, the air drywall approach uses the interior gypsum board as the main component of the wall air barrier system. Joints between the gypsum board and adjacent materials or assemblies are sealed by gaskets. In commercial construction, two different techniques are employed for using gypsum board as air barrier material: the accessible drywall and non-accessible drywall approaches. The former is similar to the air drywall approach except that high performance sealants are used instead of gaskets. In the latter approach, exterior drywall sheathing is the main component of the air barrier system; joints between boards are taped and joints between boards and other components are sealed using elastomeric membrane strips. For various types of commercial and institutional buildings, metal air barrier systems are widely used and include pre-engineered curtain walls or sheet metal walls. Masonry wall systems are regarded as still the most durable, fireproof, and soundproof wall type available but an effective air barrier system has typically been difficult to implement. Factory-made elastomeric membranes offer the potential to provide airtightness to masonry walls. These membranes are applied on the entire masonry wall surface and are used to make airtight connections with other building components. Two types of product are available: thermofusible and peel-and-stick membranes. 5 figs.

  8. Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation.

    Science.gov (United States)

    Kim, Ji Eun; Yoo, Hyun Ju; Gu, Ja Yoon; Kim, Hyun Kyung

    2016-01-01

    The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone-induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down-regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment.

  9. Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs.

    Science.gov (United States)

    Zhang, Hai-Tao; Zhang, Ping; Gao, Yi; Li, Chen-Long; Wang, Hong-Jun; Chen, Ling-Chao; Feng, Yan; Li, Rui-Yan; Li, Yong-Li; Jiang, Chuan-Lu

    2017-01-01

    Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB‑222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB‑222 was more effective than a 5 µg dose of the antibody. In addition, RB‑222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB‑222 significantly repressed VEGF expression as well as decreased MMP‑2 and MMP‑9 expression. However, it enhanced occludin and collagen‑IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

  10. Effects of topical application of aqueous solutions of hexoses on epidermal permeability barrier recovery rate after barrier disruption.

    Science.gov (United States)

    Denda, Mitsuhiro

    2011-11-01

    Previous studies have suggested that hexose molecules influence the stability of phospholipid bilayers. Therefore, the effects of topical application of all 12 stereoisomers of dextro-hexose on the epidermal barrier recovery rate after barrier disruption were evaluated. Immediately after tape stripping, 0.1 m aqueous solution of each hexose was applied on hairless mouse skin. Among the eight dextro-aldohexoses, topical application of altose, idose, mannose and talose accelerated the barrier recovery, while allose, galactose, glucose and gulose had no effect. Among the four dextro-ketohexoses, psicose, fructose, sorbose and tagatose all accelerated the barrier recovery. As the effects of hexoses on the barrier recovery rate appeared within 1 h, the mechanism is unlikely to be genomic. Instead, these hexoses may influence phase transition of the lipid bilayers of lamellar bodies and cell membrane, a crucial step in epidermal permeability barrier homeostasis. © 2011 John Wiley & Sons A/S.

  11. Advanced house air-barrier systems

    Energy Technology Data Exchange (ETDEWEB)

    Lee, R.K. [Natural Resources Canada, Ottawa, ON (Canada)

    1996-08-01

    Air barrier systems used in modern Canadian airtight homes were discussed. The Advanced Houses Program sets its airtightness requirements at 1.5 air changes per hour at 50 Pascals pressure difference (ACH{sub 5}0). In recent tests of 10 houses, it was suggested that a better airtightness level was attainable with average airtightness of about 1.0 ACH{sub 5}0. Six of the homes tested did not use the traditional polyethylene approach. Two of the houses used the airtight drywall approach, one used a foam system, and three used exterior air barriers. The advantages and disadvantages of each system was described, including cost effectiveness, cost reduction, performance and installation advantages. The confusion between an air barrier and a vapour diffusion retarder was explained. Exterior air barriers showed the greatest potential for meeting airtightness requirements at reasonable cost. 5 refs., 3 tabs.

  12. Large magnetocurrents in double-barrier tunneling transistors

    International Nuclear Information System (INIS)

    Lee, J.H.; Jun, K.-I.; Shin, K.-H.; Park, S.Y.; Hong, J.K.; Rhie, K.; Lee, B.C.

    2005-01-01

    Magnetic tunneling transistors (MTT) with double tunneling barriers are fabricated. The structure of the transistor is AFM/FM/I/FM/I/FM/AFM, and ferromagnetic layers serve as the emitter, base and collector. This double-barrier tunneling transistor (DBTT) has an advantage of controlling the potential between the base and collector, compared to the Schottky-barrier-based base and collector of MTT. We found that the collector current density of DBTT is at least 10 3 times larger than that of conventional MTT, since tunneling through AlO x barrier provides much larger current density than that through Schottky barrier

  13. Potential barrier classification by short-time measurement

    International Nuclear Information System (INIS)

    Granot, Er'el; Marchewka, Avi

    2006-01-01

    We investigate the short-time dynamics of a delta-function potential barrier on an initially confined wave packet. There are mainly two conclusions: (A) At short times the probability density of the first particles that passed through the barrier is unaffected by it. (B) When the barrier is absorptive (i.e., its potential is imaginary) it affects the transmitted wave function at shorter times than a real potential barrier. Therefore, it is possible to distinguish between an imaginary and a real potential barrier by measuring its effect at short times only on the transmitting wave function

  14. Potential barrier classification by short-time measurement

    Science.gov (United States)

    Granot, Er'El; Marchewka, Avi

    2006-03-01

    We investigate the short-time dynamics of a delta-function potential barrier on an initially confined wave packet. There are mainly two conclusions: (A) At short times the probability density of the first particles that passed through the barrier is unaffected by it. (B) When the barrier is absorptive (i.e., its potential is imaginary) it affects the transmitted wave function at shorter times than a real potential barrier. Therefore, it is possible to distinguish between an imaginary and a real potential barrier by measuring its effect at short times only on the transmitting wave function.

  15. Penetration through the Skin Barrier

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

    2016-01-01

    The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates......-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous...

  16. Big Data as Information Barrier

    Directory of Open Access Journals (Sweden)

    Victor Ya. Tsvetkov

    2014-07-01

    Full Text Available The article covers analysis of ‘Big Data’ which has been discussed over last 10 years. The reasons and factors for the issue are revealed. It has proved that the factors creating ‘Big Data’ issue has existed for quite a long time, and from time to time, would cause the informational barriers. Such barriers were successfully overcome through the science and technologies. The conducted analysis refers the “Big Data” issue to a form of informative barrier. This issue may be solved correctly and encourages development of scientific and calculating methods.

  17. Barriers and Facilitators Affecting Patient Portal Implementation from an Organizational Perspective: Qualitative Study.

    Science.gov (United States)

    Kooij, Laura; Groen, Wim G; van Harten, Wim H

    2018-05-11

    (eg, strict regulations). Both similarities and differences were found between stakeholder groups and hospital types. For example, managers and information technology employees mainly considered guaranteeing privacy and security as a predominant barrier. Financial difficulties were particularly mentioned by medical professionals and managers. Patient portal implementation is a complex process and is not only a technical process but also affects the organization and its staff. Barriers and facilitators occurred at various levels and differed among hospital types (eg, lack of accessibility) and stakeholder groups (eg, sufficient resources) in terms of several factors. Our findings underscore the importance of involving multiple stakeholders in portal implementations. We identified a set of barriers and facilitators that are likely to be useful in making strategic and efficient implementation plans. ©Laura Kooij, Wim G Groen, Wim H van Harten. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.05.2018.

  18. Deficiency of vasodilator-stimulated phosphoprotein (VASP increases blood-brain-barrier damage and edema formation after ischemic stroke in mice.

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2010-12-01

    Full Text Available Stroke-induced brain edema formation is a frequent cause of secondary infarct growth and deterioration of neurological function. The molecular mechanisms underlying edema formation after stroke are largely unknown. Vasodilator-stimulated phosphoprotein (VASP is an important regulator of actin dynamics and stabilizes endothelial barriers through interaction with cell-cell contacts and focal adhesion sites. Hypoxia has been shown to foster vascular leakage by downregulation of VASP in vitro but the significance of VASP for regulating vascular permeability in the hypoxic brain in vivo awaits clarification.Focal cerebral ischemia was induced in Vasp(-/- mice and wild-type (WT littermates by transient middle cerebral artery occlusion (tMCAO. Evan's Blue tracer was applied to visualize the extent of blood-brain-barrier (BBB damage. Brain edema formation and infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC-stained brain slices. Both mouse groups were carefully controlled for anatomical and physiological parameters relevant for edema formation and stroke outcome. BBB damage (p0.05 towards worse neurological outcomes.Our study identifies VASP as critical regulator of BBB maintenance during acute ischemic stroke. Therapeutic modulation of VASP or VASP-dependent signalling pathways could become a novel strategy to combat excessive edema formation in ischemic brain damage.

  19. Physician variation in perceived barriers to personal health

    Directory of Open Access Journals (Sweden)

    Rubenfire M

    2012-01-01

    Full Text Available Adam RB Kosteva1, Brian M Salata1, Sangeetha Mahadevan Krishnan2, Michael Howe3, Alissa Weber3, Melvyn Rubenfire2,3, Elizabeth A Jackson2,31Michigan Cardiovascular Research and Reporting Program, 2Division of Cardiovascular Medicine, 3Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USAObjective: Physicians’ personal health habits are associated with their counseling habits regarding physical activity. We sought to examine physicians’ own barriers to a healthy lifestyle by level of training and gender.Methods: Physicians at a major teaching hospital were surveyed regarding their lifestyle habits and barriers to healthy habits. The frequency of reported barriers was examined by years in practice (trainees vs staff physicians and gender.Results: 183 total responses were received. Over 20% of respondents were overweight. Work schedule was cited as the greatest barrier to regular exercise in 70.5% of respondents. Trainees were more likely to cite time constraints or cost as a barrier to a healthy diet compared to staff physicians. Staff physicians were more likely to report the time to prepare healthy foods as a barrier. For both trainees and staff physicians, time was a barrier to regular exercise. For trainees work schedule was a barrier, while both work schedule and family commitments were top barriers cited by staff physicians. Women were more likely to report family commitments as a barrier than men. Respondents suggested healthier options in vending machines and the hospital cafeteria, healthy recipes, and time and/or facilities for exercise at work as options to help overcome these barriers.Conclusion: Work schedules and family commitments are frequently reported by providers as barriers to healthy lifestyle. Efforts to reduce such barriers may lead to improved health habits among providers.Keywords: diet, exercise, counseling, prevention, gender, barriers, health

  20. Cellular mechanisms of IL-17-induced blood-brain barrier disruption.

    Science.gov (United States)

    Huppert, Jula; Closhen, Dorothea; Croxford, Andrew; White, Robin; Kulig, Paulina; Pietrowski, Eweline; Bechmann, Ingo; Becher, Burkhard; Luhmann, Heiko J; Waisman, Ari; Kuhlmann, Christoph R W

    2010-04-01

    Recently T-helper 17 (Th17) cells were demonstrated to disrupt the blood-brain barrier (BBB) by the action of IL-17A. The aim of the present study was to examine the mechanisms that underlie IL-17A-induced BBB breakdown. Barrier integrity was analyzed in the murine brain endothelial cell line bEnd.3 by measuring the electrical resistance values using electrical call impedance sensing technology. Furthermore, in-cell Western blots, fluorescence imaging, and monocyte adhesion and transendothelial migration assays were performed. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice. IL-17A induced NADPH oxidase- or xanthine oxidase-dependent reactive oxygen species (ROS) production. The resulting oxidative stress activated the endothelial contractile machinery, which was accompanied by a down-regulation of the tight junction molecule occludin. Blocking either ROS formation or myosin light chain phosphorylation or applying IL-17A-neutralizing antibodies prevented IL-17A-induced BBB disruption. Treatment of mice with EAE using ML-7, an inhibitor of the myosin light chain kinase, resulted in less BBB disruption at the spinal cord and less infiltration of lymphocytes via the BBB and subsequently reduced the clinical characteristics of EAE. These observations indicate that IL-17A accounts for a crucial step in the development of EAE by impairing the integrity of the BBB, involving augmented production of ROS.-Huppert, J., Closhen, D., Croxford, A., White, R., Kulig, P., Pietrowski, E., Bechmann, I., Becher, B., Luhmann, H. J., Waisman, A., Kuhlmann, C. R. W. Cellular mechanisms of IL-17-induced blood-brain barrier disruption.

  1. Impact of Market Regulations on the Development of Wind Power - An International Comparison

    International Nuclear Information System (INIS)

    Ackermann, Thomas; Soeder, Lennart

    2000-01-01

    This paper presents and briefly evaluates the most important existing market regulations and market schemes regarding its influence on the development of wind power. The evaluation of the existing market regulations focuses on the incentives provided by the various instruments to reduce production costs. The instruments and schemes are: Feed-in Tariffs, Net Metering, Bidding Process, Fixed Quotas, Green Certificate Trading, Green Power Exchange, Green Pricing. In addition, the impact of market regulations for international electricity markets with a power exchange are investigated. The analysis showed that new wind power generation can faces significant market barriers. (author)

  2. Swedish-Norwegian tradable green certificates: Scheme design flaws and perceived investment barriers

    International Nuclear Information System (INIS)

    Linnerud, Kristin; Simonsen, Morten

    2017-01-01

    The EU Commission recommends using market-based support schemes for renewable-electricity projects. One example is the Swedish-Norwegian tradable green certificate scheme. We examine whether design features in the Norwegian part of this scheme, specifically, the scheme's short duration and the way it is to be abruptly terminated, contribute to investors' perceptions of barriers. We apply econometric techniques on primary data collected in two surveys of Norwegian investors in hydropower, and we use real options theory to predict and interpret investors' responses. We show that: (1) immediately after the scheme was introduced, investors are eager to lock in future subsidies by investing immediately and concerned with factors that may delay the completion of their projects; (2) as the certificate deadline neared, investors have become increasingly pessimistic and concerned with economic and risk barriers. Investors in big hydropower plants with regulation reservoirs are particularly concerned with the risk of not completing their projects in time to gain the right to sell certificates. These findings are consistent with the predicted responses to the scheme design derived from real options theory. In contrast to earlier studies, we find no difference in responses to the scheme design across investor types. - Highlights: • The Swedish-Norwegian tradable green certificate scheme is intended to promote cost-efficiency. • We examine the optimism about and barriers against investing in new hydropower projects in Norway. • We find that scheme design may have contributed to barriers against Norwegian hydropower projects. • Thus, scheme design flaws may have prevented the scheme from working as intended. • These findings are consistent with real options theory predictions.

  3. Apoptosis of Endothelial Cells by 13-HPODE Contributes to Impairment of Endothelial Barrier Integrity

    Directory of Open Access Journals (Sweden)

    Valerie E. Ryman

    2016-01-01

    Full Text Available Inflammation is an essential host response during bacterial infections such as bovine mastitis. Endothelial cells are critical for an appropriate inflammatory response and loss of vascular barrier integrity is implicated in the pathogenesis of Streptococcus uberis-induced mastitis. Previous studies suggested that accumulation of linoleic acid (LA oxygenation products derived from 15-lipoxygenase-1 (15-LOX-1 metabolism could regulate vascular functions. The initial LA derivative from the 15-LOX-1 pathway, 13-hydroperoxyoctadecadienoic acid (HPODE, can induce endothelial death, whereas the reduced hydroxyl product, 13-hydroxyoctadecadienoic acid (HODE, is abundantly produced during vascular activation. However, the relative contribution of specific LA-derived metabolites on impairment of mammary endothelial integrity is unknown. Our hypothesis was that S. uberis-induced LA-derived 15-LOX-1 oxygenation products impair mammary endothelial barrier integrity by apoptosis. Exposure of bovine mammary endothelial cells (BMEC to S. uberis did not increase 15-LOX-1 LA metabolism. However, S. uberis challenge of bovine monocytes demonstrated that monocytes may be a significant source of both 13-HPODE and 13-HODE during mastitis. Exposure of BMEC to 13-HPODE, but not 13-HODE, significantly reduced endothelial barrier integrity and increased apoptosis. Changing oxidant status by coexposure to an antioxidant during 13-HPODE treatment prevented adverse effects of 13-HPODE, including amelioration of apoptosis. A better understanding of how the oxidant status of the vascular microenvironment impacts endothelial barrier properties could lead to more efficacious treatments for S. uberis mastitis.

  4. Structuring unbreakable hydrophobic barriers in paper

    Science.gov (United States)

    Nargang, Tobias M.; Kotz, Frederik; Rapp, Bastian E.

    2018-02-01

    Hydrophobic barriers are one of the key elements of microfluidic paper based analytical devices (μPADs).μPADs are simple and cost efficient and they can be carried out without the need of high standard laboratories. To carry out such a test a method is needed to create stable hydrophobic barriers. Commonly used methods like printing wax or polystyrene have the major drawback that these barriers are stiff and break if bended which means they will no longer be able to retain a liquid sample. Here we present silanes to structure hydrophobic barriers via polycondensation and show a silanization method which combines the advantages of flexible silane/siloxane layers with the short processing times of UV-light based structuring. The barriers are created by using methoxy silanes which are mixed with a photo acid generator (PAG) as photoinitiator. Also a photosensitizer was given to the mixture to increase the effectiveness of the PAG. After the PAG is activated by UV-light the silane is hydrolyzed and coupled to the cellulose via polycondensation. The created hydrophobic barriers are highly stable and do not break if being bended.

  5. The effects of temperature on Schottky diode barrier height and evidence of multiple barrier

    International Nuclear Information System (INIS)

    Rabah, K.V.O.

    1994-07-01

    Experimental study of Capacitance-Voltage-Temperature (C-V-T) plots, Current-Voltage-Temperature (I-V-T) characteristics have been undertaken in order to determine the height of the Schottky barrier. The results of the barrier height obtained by the above two methods were found to differ as well as vary with temperature change. In view of this discrepancy in barrier height values, two further experiments were performed: one on activation energy (I-T) plots and the other on pulsed (I-V-T) characteristics, and the results were found to show a similar trend. The Schottky diode studied was a 30CP040. (author). 23 refs, 9 figs, 3 tabs

  6. Role of lipids in the formation and maintenance of the cutaneous permeability barrier.

    Science.gov (United States)

    Feingold, Kenneth R; Elias, Peter M

    2014-03-01

    The major function of the skin is to form a barrier between the internal milieu and the hostile external environment. A permeability barrier that prevents the loss of water and electrolytes is essential for life on land. The permeability barrier is mediated primarily by lipid enriched lamellar membranes that are localized to the extracellular spaces of the stratum corneum. These lipid enriched membranes have a unique structure and contain approximately 50% ceramides, 25% cholesterol, and 15% free fatty acids with very little phospholipid. Lamellar bodies, which are formed during the differentiation of keratinocytes, play a key role in delivering the lipids from the stratum granulosum cells into the extracellular spaces of the stratum corneum. Lamellar bodies contain predominantly glucosylceramides, phospholipids, and cholesterol and following the exocytosis of lamellar lipids into the extracellular space of the stratum corneum these precursor lipids are converted by beta glucocerebrosidase and phospholipases into the ceramides and fatty acids, which comprise the lamellar membranes. The lipids required for lamellar body formation are derived from de novo synthesis by keratinocytes and from extra-cutaneous sources. The lipid synthetic pathways and the regulation of these pathways are described in this review. In addition, the pathways for the uptake of extra-cutaneous lipids into keratinocytes are discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. Published by Elsevier B.V.

  7. Water and contaminant movement: migration barriers

    International Nuclear Information System (INIS)

    Lane, L.J.; Nyhan, J.W.

    1984-11-01

    Migration barriers are used in shallow land burial facilities to slow or stop the movement of water and contaminants and are discussed here as a single component embedded in a complex environmental system. Analytical solutions to solute transport equations are used to approximate the behavior of migration barriers and to derive design criteria for control of subsurface water and contaminant migration. Various types of migration barriers are compared and design recommendations are made for shallow land burial trench caps and liners. Needed improvements and suggested field experiments for future designs of migration barriers are then discussed relative to the management of low-level radioactive wastes

  8. Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers

    Directory of Open Access Journals (Sweden)

    Jessica L Williams

    2014-05-01

    Full Text Available In the adult central nervous system (CNS, chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

  9. Barriers in the energy of deformed nuclei

    Directory of Open Access Journals (Sweden)

    V. Yu. Denisov

    2014-06-01

    Full Text Available Interaction energy between two nuclei considering to their deformations is studied. Coulomb and nuclear in-teraction energies, as well as the deformation energies of both nuclei, are taken into account at evaluation of the interaction energy. It is shown that the barrier related to the interaction energy of two nuclei depends on the de-formations and the height of the minimal barrier is evaluated. It is obtained that the heavier nucleus-nucleus sys-tems have large deformation values at the lowest barrier. The difference between the barrier between spherical nuclei and the lowest barrier between deformed nuclei increases with the mass and the charge of the interacting nuclei.

  10. Model assessment of protective barrier designs

    International Nuclear Information System (INIS)

    Fayer, M.J.; Conbere, W.; Heller, P.R.; Gee, G.W.

    1985-11-01

    A protective barrier is being considered for use at the Hanford site to enhance the isolation of previously disposed radioactive wastes from infiltrating water, and plant and animal intrusion. This study is part of a research and development effort to design barriers and evaluate their performance in preventing drainage. A fine-textured soil (the Composite) was located on the Hanford site in sufficient quantity for use as the top layer of the protective barrier. A number of simulations were performed by Pacific Northwest Laboratory to analyze different designs of the barrier using the Composite soil as well as the finer-textured Ritzville silt loam and a slightly coarser soil (Coarse). Design variations included two rainfall rates (16.0 and 30.1 cm/y), the presence of plants, gravel mixed into the surface of the topsoil, an impermeable boundary under the topsoil, and moving the waste form from 10 to 20 m from the barrier edge. The final decision to use barriers for enhanced isolation of previously disposed wastes will be subject to decisions resulting from the completion of the Hanford Defense Waste Environmental Impact Statement, which addresses disposal of Hanford defense high-level and transuranic wastes. The one-dimensional simulation results indicate that each of the three soils, when used as the top layer of the protective barrier, can prevent drainage provided plants are present. Gravel amendments to the upper 30 cm of soil (without plants) reduced evaporation and allowed more water to drain

  11. [Blood-brain barrier part III: therapeutic approaches to cross the blood-brain barrier and target the brain].

    Science.gov (United States)

    Weiss, N; Miller, F; Cazaubon, S; Couraud, P-O

    2010-03-01

    Over the last few years, the blood-brain barrier has come to be considered as the main limitation for the treatment of neurological diseases caused by inflammatory, tumor or neurodegenerative disorders. In the blood-brain barrier, the close intercellular contact between cerebral endothelial cells due to tight junctions prevents the passive diffusion of hydrophilic components from the bloodstream into the brain. Several specific transport systems (via transporters expressed on cerebral endothelial cells) are implicated in the delivery of nutriments, ions and vitamins to the brain; other transporters expressed on cerebral endothelial cells extrude endogenous substances or xenobiotics, which have crossed the cerebral endothelium, out of the brain and into the bloodstream. Recently, several strategies have been proposed to target the brain, (i) by by-passing the blood-brain barrier by central drug administration, (ii) by increasing permeability of the blood-brain barrier, (iii) by modulating the expression and/or the activity of efflux transporters, (iv) by using the physiological receptor-dependent blood-brain barrier transport, and (v) by creating new viral or chemical vectors to cross the blood-brain barrier. This review focuses on the illustration of these different approaches. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

  12. Alterations in Factors Involved in Differentiation and Barrier Function in the Epithelium in Oral and Genital Lichen Planus.

    Science.gov (United States)

    Danielsson, Karin; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2017-02-08

    Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

  13. HRE-Pond Cryogenic Barrier Technology Demonstration: Pre- and Post-Barrier Hydrologic Assessment

    International Nuclear Information System (INIS)

    Moline, G.R.

    1999-01-01

    The Homogeneous Reactor Experiment (HRE) Pond is the site of a former impoundment for radioactive wastes on the Oak Ridge Reservation (ORR) in east Tennessee. The pond received radioactive wastes from 1957 to 1962, and was subsequently drained, filled with soil, and covered with an asphalt cap. The site is bordered to the east and south by an unnamed stream that contains significant concentrations of radioactive contaminants, primarily 90 Sr. Because of the proximity of the stream to the HRE disposal site and the probable flow of groundwater from the site to the stream, it was hypothesized that the HRE Pond has been a source of contamination to the creek. The HRE-Pond was chosen as the site of a cryogenic barrier demonstration to evaluate this technology as a means for rapid, temporary isolation of contaminants in the type of subsurface environment that exists on the ORR. The cryogenic barrier is created by the circulation of liquid CO 2 through a system of thermoprobes installed in boreholes which are backfilled with sand. The probes cool the subsurface, creating a vertical ice wall by freezing adjacent groundwater, effectively surrounding the pond on four sides. The purpose of this investigation was to evaluate the hydrologic conditions within and around the pond prior to, during, and after the cryogenic barrier emplacement. The objectives were (1) to provide a hydrologic baseline for post-banner performance assessment, (2) to confirm that the pond is hydraulically connected to the surrounding sediments, (3) to determine the likely contaminant exit pathways from the pond, and (4) to measure changes in hydrologic conditions after barrier emplacement in order to assess the barrier performance. Because relatively little information about the subsurface hydrology and the actual configuration of the pond existed, data from multiple sources was required to reconstruct this complex system

  14. Permeability Barrier Generation in the Martian Lithosphere

    Science.gov (United States)

    Schools, Joe; Montési, Laurent

    2015-11-01

    Permeability barriers develop when a magma produced in the interior of a planet rises into the cooler lithosphere and crystallizes more rapidly than the lithosphere can deform (Sparks and Parmentier, 1991). Crystallization products may then clog the porous network in which melt is propagating, reducing the permeability to almost zero, i.e., forming a permeability barrier. Subsequent melts cannot cross the barrier. Permeability barriers have been useful to explain variations in crustal thickness at mid-ocean ridges on Earth (Magde et al., 1997; Hebert and Montési, 2011; Montési et al., 2011). We explore here under what conditions permeability barriers may form on Mars.We use the MELTS thermodynamic calculator (Ghiorso and Sack, 1995; Ghiorso et al., 2002; Asimow et al., 2004) in conjunction with estimated Martian mantle compositions (Morgan and Anders, 1979; Wänke and Dreibus, 1994; Lodders and Fegley, 1997; Sanloup et al., 1999; Taylor 2013) to model the formation of permeability barriers in the lithosphere of Mars. In order to represent potential past and present conditions of Mars, we vary the lithospheric thickness, mantle potential temperature (heat flux), oxygen fugacity, and water content.Our results show that permeability layers can develop in the thermal boundary layer of the simulated Martian lithosphere if the mantle potential temperature is higher than ~1500°C. The various Martian mantle compositions yield barriers in the same locations, under matching variable conditions. There is no significant difference in barrier location over the range of accepted Martian oxygen fugacity values. Water content is the most significant influence on barrier development as it reduces the temperature of crystallization, allowing melt to rise further into the lithosphere. Our lower temperature and thicker lithosphere model runs, which are likely the most similar to modern Mars, show no permeability barrier generation. Losing the possibility of having a permeability

  15. Vertical barriers with increased sorption capacities

    International Nuclear Information System (INIS)

    Bradl, H.B.

    1997-01-01

    Vertical barriers are commonly used for the containment of contaminated areas. Due to the very small permeability of the barrier material which is usually in the order of magnitude of 10-10 m/s or less the advective contaminant transport can be more or less neglected. Nevertheless, there will always be a diffusive contaminant transport through the barrier which is caused by the concentration gradient. Investigations have been made to increase the sorption capacity of the barrier material by adding substances such as organoclays, zeolites, inorganic oxides and fly ashes. The contaminants taken into account where heavy metals (Pb) and for organic contaminants Toluole and Phenantrene. The paper presents results of model calculations and experiments. As a result, barrier materials can be designed 'tailor-made' depending on the individual contaminant range of each site (e.g. landfills, gasworks etc.). The parameters relevant for construction such as rheological properties, compressive strength and permeability are not affected by the addition of the sorbents

  16. Barrier bucket experiment at the AGS

    Directory of Open Access Journals (Sweden)

    M. Fujieda

    1999-12-01

    Full Text Available A barrier bucket experiment with two dedicated barrier cavities was performed at the Brookhaven AGS. One of the barrier cavities was a magnetic alloy (MA–loaded cavity and the other was a ferrite-loaded cavity. They generated a single sine wave with a peak voltage of 40 kV at a repetition rate of 351 kHz. A barrier rf system was established with these cavities and five bunches from the AGS booster were accumulated. A total of 3×10^{13} protons were stored without beam loss, and were successfully rebunched and accelerated. The longitudinal emittance growth was observed during accumulation by the barrier bucket, the blowup factor of which was about 3. The longitudinal mismatch between the rf bucket and the beam bunch was the main reason for the emittance growth. The potential distortions by beam loading of the ferrite cavity and the overshooting voltage of the MA cavity disturbed the smooth debunching.

  17. Engineering kinetic barriers in copper metallization

    International Nuclear Information System (INIS)

    Huang Hanchen; Wei, H.L.; Woo, C.H.; Zhang, X.X.

    2002-01-01

    In metallization processes of integrated circuits, it is desirable to deposit the metal lines (aluminum or copper) fast and at low temperatures. However, the lines (films) usually consist of undesirable columns and voids, because of the absence of sufficient diffusion--a direct result of large kinetic barriers. Following the proposal and realization of the three-dimensional Ehrlich-Schwoebel (3D ES) barrier, we present here a method to engineer this kinetic barrier so as to improve quality of deposited copper films. We deposit copper films by magnetron sputtering, characterize the film structure and texture by using the scanning electron microscope and the x-ray diffraction, respectively. Taking indium as surfactant during copper deposition, we have achieved much better density and bottom coverage of copper filled trenches. The characterizations show that the improvement is the result of the 3D ES barrier reduction caused by indium addition. Engineering the 3D ES barrier therefore leads to improved film quality

  18. A cross-cultural investigation into the dimensional structure and stability of the Barriers to Research and Utilization Scale (BARRIERS Scale).

    Science.gov (United States)

    Williams, Brett; Brown, Ted; Costello, Shane

    2015-10-24

    It is important that scales exhibit strong measurement properties including those related to the investigation of issues that impact evidence-based practice. The validity of the Barriers to Research Utilization Scale (BARRIERS Scale) has recently been questioned in a systematic review. This study investigated the dimensional structure and stability of the 28 item BARRIERS Scale when completed by three groups of participants from three different cross-cultural environments. Data from the BARRIERS Scale completed by 696 occupational therapists from Australia (n = 137), Taiwan (n = 413), and the United Kingdom (n = 144) were analysed using principal components analysis, followed by Procrustes Transformation. Poorly fitting items were identified by low communalities, cross-loading, and theoretically inconsistent primary loadings, and were systematically removed until good fit was achieved. The cross-cultural stability of the component structure of the BARRIERS Scale was examined. A four component, 19 item version of the BARRIERS Scale emerged that demonstrated an improved dimensional fit and stability across the three participant groups. The resulting four components were consistent with the BARRIERS Scale as originally conceptualised. Findings from the study suggest that the four component, 19 item version of the BARRIERS Scale is a robust and valid measure for identifying barriers to research utilization for occupational therapists in paediatric health care settings across Australia, United Kingdom, and Taiwan. The four component 19 item version of the BARRIERS Scale exhibited good dimensional structure, internal consistency, and stability.

  19. Barrier experiment: Shock initiation under complex loading

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-01-12

    The barrier experiments are a variant of the gap test; a detonation wave in a donor HE impacts a barrier and drives a shock wave into an acceptor HE. The question we ask is: What is the trade-off between the barrier material and threshold barrier thickness to prevent the acceptor from detonating. This can be viewed from the perspective of shock initiation of the acceptor subject to a complex pressure drive condition. Here we consider key factors which affect whether or not the acceptor undergoes a shock-to-detonation transition. These include the following: shock impedance matches for the donor detonation wave into the barrier and then the barrier shock into the acceptor, the pressure gradient behind the donor detonation wave, and the curvature of detonation front in the donor. Numerical simulations are used to illustrate how these factors affect the reaction in the acceptor.

  20. Nurse-patient communication barriers in Iranian nursing.

    Science.gov (United States)

    Anoosheh, M; Zarkhah, S; Faghihzadeh, S; Vaismoradi, M

    2009-06-01

    Providing effective communication with patients is an essential aspect of nursing care. Understanding the barriers that inhibit nurse-patient communication can provide an opportunity to eliminate them. To investigate nurse-patient and environment-related communication barriers perceived by patients and nurses in Iranian nursing. A descriptive survey was carried out in three randomly selected educational hospitals in a large urban city in Iran. Data were collected by questionnaire; the study sample consisted of 61 patients and 75 nurses. Participants were asked to rate the importance of each communication barriers item. Finally, data were analysed using descriptive statistics, and to compare the perceived importance of communication barriers between patients and nurses, item means were calculated and the t-test for independent samples was applied. Similarities and differences between the two groups were identified. According to nurses' views, 'heavy nursing workload', 'hard nursing tasks' and 'lack of welfare facilities for nurses' were the main communication barriers. From patients' views, 'unfamiliarity of nurses with dialect', 'having contagious diseases' and 'sex differences between nurses and patients' were determined as the main communication barriers. The shared communication barriers were 'age difference', 'social class difference' and 'having contagious diseases'. It can be concluded that nursing managers and healthcare system planners should focus on eliminating or modifying the barriers stated by the two groups, particularly the shared ones. It is suggested that understanding the cultural aspects of nurse-patient communication barriers in various contexts can help nurses. The study relied on self-report by a limited sample of nurses and patients. The responses should now be tested by a larger sample and then by empirical research into actual practice in order to test whether the nurses' and patients' perceived ideas of communication barriers are

  1. Barriers affecting adherence to radiation treatment and strategies to overcome those barriers.

    Science.gov (United States)

    Rangarajan, R; Jayaraman, K

    2017-01-01

    The WHO defines adherence as the extent to which a patient's behavior coincides with recommendations from a health-care provider. Nonadherence to cancer treatment has a major impact on the therapeutic outcome. To assess the prevalence of nonadherence to radiation regimen and to analyze the factors that affect adherence to cancer treatment. Patients receiving radiation treatment in our hospital were screened for adherence to appointment keeping and to the prescribed radiation regimen and patients who had unplanned treatment breaks during treatment were interviewed. Between January and July 2013, we identified 61 patients who had unplanned breaks during treatment. We analyzed the social, emotional, educational, economic, and therapeutic barriers that led to nonadherence. Of the 61 patients who had unplanned breaks during treatment, 54% were males and 46% were females. Fifty-seven percent of patients had head and neck cancers and 25% had gynecological cancers. Seventy-one percent of patients were planned for concurrent chemoradiation. The number of days of unplanned treatment breaks ranged from 3 to 27 days. Social and therapeutic barriers were found to be the most common factor that led to nonadherence in these patients. Identification of barriers that lead to nonadherence, designing strategies to overcome such barriers and effective communication becomes imperative to ensure uninterrupted treatment. Based on the above analysis, we have designed several strategies to improve adherence to treatment among our patients.

  2. Barriers and post-closure monitoring (AL121125)

    International Nuclear Information System (INIS)

    Bostick, K.V.; Janecky, D.

    1995-01-01

    This project focuses on the rapid implementation of near-surface barriers, biotreatment, and post-closure monitoring technology. It uses water-permeable and biologic barriers that chemically capture and/or degrade contaminants without significantly altering the natural water flow regime. Barrier approaches are being tested for two different applications. The first is the use of barriers for confinement of chemical contaminants for in-trench treatments with leach systems or an in-place bioreactor. The second is an enhancement of the current practice of emplacing grout or clay slurry walls into direct horizontal surface and subsurface water flows around a contaminated area by integrating permeable reactive barriers and petroleum reservoir gel/foam/polymer technology

  3. Energy barriers in patterned media

    NARCIS (Netherlands)

    de Vries, Jeroen

    2013-01-01

    Due to the fact that thermal activation aids in overcoming the energy barrier, the required field for reversal varies from instance to instance for the same island. This thermally induced switching field distribution can be used to determine the difference in energy barrier of magneticallyweak and

  4. SOME OBSERVATIONS ON THE DESIGN OF NOISE BARRIERS

    OpenAIRE

    Arkadiusz BOCZKOWSKI

    2013-01-01

    The issue connected with effectiveness of noise barriers has been the subject of numerous considerations among acousticians. On the one hand, noise barriers are still the most popular and the most frequently used protection against traffic noise, on the other hand, however, the excessive number of noise barriers and the results of research focusing on effectiveness of the existing barriers make us reflect whether it is reasonable to use them. Very often low effectiveness of noise barriers is ...

  5. Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

    Science.gov (United States)

    Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

    2017-04-03

    Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Numerical simulation of flood barriers

    Science.gov (United States)

    Srb, Pavel; Petrů, Michal; Kulhavý, Petr

    This paper deals with testing and numerical simulating of flood barriers. The Czech Republic has been hit by several very devastating floods in past years. These floods caused several dozens of causalities and property damage reached billions of Euros. The development of flood measures is very important, especially for the reduction the number of casualties and the amount of property damage. The aim of flood control measures is the detention of water outside populated areas and drainage of water from populated areas as soon as possible. For new flood barrier design it is very important to know its behaviour in case of a real flood. During the development of the barrier several standardized tests have to be carried out. Based on the results from these tests numerical simulation was compiled using Abaqus software and some analyses were carried out. Based on these numerical simulations it will be possible to predict the behaviour of barriers and thus improve their design.

  7. PIWIL1/piRNA-DQ593109 Regulates the Permeability of the Blood-Tumor Barrier via the MEG3/miR-330-5p/RUNX3 Axis

    Directory of Open Access Journals (Sweden)

    Shuyuan Shen

    2018-03-01

    Full Text Available The blood-tumor barrier (BTB restricts the efficient delivery of anti-glioma drugs to cranial glioma tissues. Increased BTB permeability may allow greater delivery of the therapeutic agents. Increasing evidence has revealed that PIWI proteins and PIWI-interacting RNAs (piRNAs play an important role in tumor progression. However, whether PIWI proteins and piRNAs regulate BTB permeability remains unclear. In the present study, we demonstrated that the PIWIL1/piRNA-DQ593109 (piR-DQ593109 complex was the predominant regulator of BTB permeability. Briefly, PIWIL1 was upregulated in glioma endothelial cells (GECs. Furthermore, piR-DQ593109 was also overexpressed in GECs, as revealed via a piRNA microarray. Downregulation of PIWIL1 or piR-DQ593109 increased the permeability of the BTB. Moreover, PIWIL1 and piR-DQ593109, which formed a piRNA-induced silencing complex, degraded the long non-coding RNA maternally expressed 3 (MEG3 in a sequenced-dependent manner. Furthermore, restoring MEG3 released post-transcriptional inhibition of Runt related transcription factor 3 (RUNX3 by sponging miR-330-5p. In addition, RUNX3 bounded to the promoter regions and reduced the promoter activities of ZO-1, occludin, and claudin-5, which significantly impaired the expression levels of ZO-1, occludin, and claudin-5. In conclusion, downregulating PIWIL1 and piR-DQ593109 increased BTB permeability through the MEG3/miR-330-5p/RUNX3 axis. These data may provide insight into glioma treatment.

  8. A Learner Perspective on Barriers to E-Learning

    Science.gov (United States)

    Becker, Karen; Newton, Cameron; Sawang, Sukanlaya

    2013-01-01

    This study aims to identify and categorize barriers to e-learning adoption and the relative impact of those barriers on learners. It contributes to the understanding of learner perceptions of barriers, the different types of barriers and their relative importance. This study used a quantitative methodology grounded in previous literature. The…

  9. Field study plan for alternate barriers

    International Nuclear Information System (INIS)

    Freeman, H.D.; Gee, G.W.; Relyea, J.F.

    1989-05-01

    Pacific Northwest Laboratory (PNL) is providing technical assistance in selecting, designing, evaluating, and demonstrating protective barriers. As part of this technical assistance effort, asphalt, clay, and chemical grout will be evaluated for use as alternate barriers. The purpose of the subsurface layer is to reduce the likelihood that extreme events (i.e., 100-year maximum storms, etc.) will cause significant drainage through the barrier. The tests on alternate barriers will include laboratory and field analysis of the subsurface layer performance. This field test plan outlines the activities required to test and design subsurface moisture barriers. The test plan covers activities completed in FY 1988 and planned through FY 1992 and includes a field-scale test of one or more of the alternate barriers to demonstrate full-scale application techniques and to provide performance data on a larger scale. Tests on asphalt, clay, and chemical grout were initiated in FY 1988 in small (30.5 cm diameter) tube-layer lysimeters. The parameters used for testing the materials were different for each one. The tests had to take into account the differences in material characteristics and response to change in conditions, as well as information provided by previous studies. 33 refs., 8 figs., 1 tab

  10. Wildland fire as a self-regulating mechanism: the role of previous burns and weather in limiting fire progression

    Science.gov (United States)

    Sean A. Parks; Lisa M. Holsinger; Carol Miller; Cara R. Nelson

    2015-01-01

    Theory suggests that natural fire regimes can result in landscapes that are both self-regulating and resilient to fire. For example, because fires consume fuel, they may create barriers to the spread of future fires, thereby regulating fire size. Top-down controls such as weather, however, can weaken this effect. While empirical examples demonstrating this pattern-...

  11. Numerical simulations of capillary barrier field tests

    International Nuclear Information System (INIS)

    Morris, C.E.; Stormont, J.C.

    1997-01-01

    Numerical simulations of two capillary barrier systems tested in the field were conducted to determine if an unsaturated flow model could accurately represent the observed results. The field data was collected from two 7-m long, 1.2-m thick capillary barriers built on a 10% grade that were being tested to investigate their ability to laterally divert water downslope. One system had a homogeneous fine layer, while the fine soil of the second barrier was layered to increase its ability to laterally divert infiltrating moisture. The barriers were subjected first to constant infiltration while minimizing evaporative losses and then were exposed to ambient conditions. The continuous infiltration period of the field tests for the two barrier systems was modelled to determine the ability of an existing code to accurately represent capillary barrier behavior embodied in these two designs. Differences between the field test and the model data were found, but in general the simulations appeared to adequately reproduce the response of the test systems. Accounting for moisture retention hysteresis in the layered system will potentially lead to more accurate modelling results and is likely to be important when developing reasonable predictions of capillary barrier behavior

  12. Nested barriers to low-carbon infrastructure investment

    Science.gov (United States)

    Granoff, Ilmi; Hogarth, J. Ryan; Miller, Alan

    2016-12-01

    Low-carbon, 'green' economic growth is necessary to simultaneously improve human welfare and avoid the worst impacts of climate change and environmental degradation. Infrastructure choices underpin both the growth and the carbon intensity of the economy. This Perspective explores the barriers to investing in low-carbon infrastructure and some of the policy levers available to overcome them. The barriers to decarbonizing infrastructure 'nest' within a set of barriers to infrastructure development more generally that cause spending on infrastructure--low-carbon or not--to fall more than 70% short of optimal levels. Developing countries face additional barriers such as currency and political risks that increase the investment gap. Low-carbon alternatives face further barriers, such as commercialization risk and financial and public institutions designed for different investment needs. While the broader barriers to infrastructure investment are discussed in other streams of literature, they are often disregarded in literature on renewable energy diffusion or climate finance, which tends to focus narrowly on the project costs of low- versus high-carbon options. We discuss how to overcome the barriers specific to low-carbon infrastructure within the context of the broader infrastructure gap.

  13. [Prevalence of barriers for physical activity in adolescents].

    Science.gov (United States)

    Santos, Mariana Silva; Hino, Adriano Akira Ferreira; Reis, Rodrigo Siqueira; Rodriguez-Añez, Ciro Romélio

    2010-03-01

    The aim of this study was to analyze the prevalence and association of barriers to physical activity among adolescents. This cross-sectional study evaluated a representative sample of public high school students in Curitiba-PR, Brazil. A total of 1,609 school adolescents (59.7% male) between 14 and 18 years of age answered a questionnaire on physical activity status and barriers to physical activity. Logistic regressions were conducted for each barrier investigated to verify the association between the prevalence of barriers and physical activity, adjusting for confounding variables (age and socioeconomic status). Analyses were done separately for boys and girls. Only 22% of boys and 9% of girls achieved the current physical activity recommendation. Among the 12 barriers investigated, only "there is nobody to take" did not differ between boys and girls. The perception of barriers was higher for girls than boys (p barriers. "Lack of friends company" and "feel lazy" were the barriers most often reported by boys (30.4%) and girls (51.8%) respectively; however, the barrier most strongly associated with prevalence of physical inactivity was "prefer to do other things" for both boys (OR = 5.02 (2.69 - 9.37); p barriers for the practice of physical activity were more prevalent in girls and differed as to the extent of importance between genders.

  14. Perceptions regarding strategic and structural entry barriers

    NARCIS (Netherlands)

    Lutz, C.H.M.; Kemp, R.G.M.; Dijkstra, S.G.

    2010-01-01

    This article uses factor analysis to identify the underlying dimensions of strategic and structural entry barriers. We find that, in the perception of firms, both types of barriers are important and that the effectiveness of strategic barriers depends on attributes of the market structure. Based on

  15. Perceptions regarding strategic and structural entry barriers

    NARCIS (Netherlands)

    Lutz, Clemens H. M.; Kemp, Ron G. M.; Dijkstra, S. Gerhard

    This article uses factor analysis to identify the underlying dimensions of strategic and structural entry barriers. We find that, in the perception of firms, both types of barriers are important and that the effectiveness of strategic barriers depends on attributes of the market structure. Based on

  16. Differential Rollover Risk in Vehicle-to-Traffic Barrier Collisions

    Science.gov (United States)

    Gabauer, Douglas J.; Gabler, Hampton C.

    2009-01-01

    In the roadside safety community, there has been debate over the influence of vehicle and barrier type on rollover rates in traffic barrier crashes. This study investigated rollover rates between sport utility vehicles (SUVs), pickup trucks, and cars in vehicle-traffic barrier crashes and has examined the effect of barrier type on rollover risk for concrete barrier and metal barrier impacts. The analysis included 955 barrier impact cases that were selected from 11-years of in-depth crash data available through the National Automotive Sampling System (NASS) / Crashworthiness Data System (CDS). In real world tow-away level longitudinal barrier collisions, the most important predictors of vehicle rollover were found to be vehicle type and whether the vehicle was tracking prior to barrier impact. Based on binary logistic regression, SUVs were found to have 8 times the risk of rollover as cars in barrier impacts. Although pickups were found to have an increased risk of rollover compared to cars, the risk was not as pronounced as that found for SUVs. This finding has direct implications for the full scale crash testing of longitudinal barriers as the testing procedures have been predicated on the assumption that the pickup truck provides a critical or worst case impact scenario. In towaway crashes, our study does not support the notion that concrete barriers have a higher risk of vehicle rollover than metal beam barriers. PMID:20184839

  17. Performance of dynamic safety barriers-Structuring, modelling and visualization

    OpenAIRE

    Wikdahl, Olga

    2014-01-01

    The main objective of this master thesis is to discuss performance of dynamic safety barriers. A comprehensive literature review is performed in order to get understanding what dynamic safety barrier is. Three different concepts of dynamic safety barriers based on various meanings of dynamic were derived from the literature review: - dynamic safety barriers related to motion or physical force - dynamic safety barriers as updated barriers from dynamic risk analysis - dynamic safety ...

  18. Simulating complex noise barrier reflections

    NARCIS (Netherlands)

    Eerden, F.J.M. van der; Lutgendorf, D.; Roo, F. de

    2011-01-01

    Within the EU FP7 QUIESST project, QUIeting the Environment for a Sustainable Surface Transport, a test method is being developed for the reflectivity of noise barriers. The method needs to account for a complex shape of barriers and the use of various types of absorbing materials. The performance

  19. K-Basin isolation barrier seal

    International Nuclear Information System (INIS)

    Ruff, E.S.

    1994-10-01

    This report documents various aspects of the design, analysis, procurement, and fabrication of the hydraulic seal on the isolation barriers to be installed in the 100-K Area spent nuclear fuel basin. The isolation barrier is used to keep water in the basin in the event of an earthquake

  20. In the interest of food safety: a qualitative study investigating communication and trust between food regulators and food industry in the UK, Australia and New Zealand.

    Science.gov (United States)

    Meyer, Samantha B; Wilson, Annabelle M; Calnan, Michael; Henderson, Julie; Coveney, John; McCullum, Dean; Pearce, Alex R; Ward, Paul; Webb, Trevor

    2017-02-13

    Food regulatory bodies play an important role in public health, and in reducing the costs of food borne illness that are absorbed by both industry and government. Regulation in the food industry involves a relationship between regulators and members of the industry, and it is imperative that these relationships are built on trust. Research has shown in a variety of contexts that businesses find the most success when there are high levels of trust between them and their key stakeholders. An evidence-based understanding of the barriers to communication and trust is imperative if we are to put forward recommendations for facilitating the (re)building of trusting and communicative relationships. We present data from 72 interviews with regulators and industry representatives regarding their trust in and communication with one another. Interviews were conducted in the UK, New Zealand, and Australia in 2013. Data identify a variety of factors that shape the dynamic and complex relationships between regulators and industry, as well as barriers to communication and trust between the two parties. Novel in our approach is our emphasis on identifying solutions to these barriers from the voices of industry and regulators. We provide recommendations (e.g., development of industry advisory boards) to facilitate the (re)building of trusting and communicative relationships between the two parties.

  1. On the evolution of a holocene barrier coast

    DEFF Research Database (Denmark)

    Fruergaard, Mikkel

    in a distinct stratal stacking pattern of each of the investigated coastal barrier systems. We conclude that the overall infilling of the barrier systems over the Holocene was mainly controlled by sea-level rise and sediment supply. However, major storms and tidal channel migration have greatly affected......This thesis investigates the sedimentary evolution of a Holocene barrier coast with special focus on how barrier system stratigraphy is affected by changes in sea-level and sediment supply. Coastal barrier systems comprise about 13% of the world’s coastlines and they are mportant components...... of the stratigraphic record of the Earth. Sea-level rise and sediment supply are the two most important factors controlling barrier system evolution. Detailed depositional reconstructions of a number of barrier systems from the Danish Wadden Sea area have been carried out in order to evaluate the sedimentary effects...

  2. 49 CFR 587.18 - Dimensions of fixed rigid barrier.

    Science.gov (United States)

    2010-10-01

    ... TRAFFIC SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) DEFORMABLE BARRIERS Offset Deformable Barrier § 587.18 Dimensions of fixed rigid barrier. (a) The fixed rigid barrier has a mass of not... 49 Transportation 7 2010-10-01 2010-10-01 false Dimensions of fixed rigid barrier. 587.18 Section...

  3. Investigation of microstructure and properties of ultrathin graded ZrNx self-assembled diffusion barrier in deep nano-vias prepared by plasma ion immersion implantation

    Science.gov (United States)

    Zou, Jianxiong; Liu, Bo; Lin, Liwei; Lu, Yuanfu; Dong, Yuming; Jiao, Guohua; Ma, Fei; Li, Qiran

    2018-01-01

    Ultrathin graded ZrNx self-assembled diffusion barriers with controllable stoichiometry was prepared in Cu/p-SiOC:H interfaces by plasma immersion ion implantation (PIII) with dynamic regulation of implantation fluence. The fundamental relationship between the implantation fluence of N+ and the stoichiometry and thereby the electrical properties of the ZrNx barrier was established. The optimized fluence of a graded ZrN thin film with gradually decreased Zr valence was obtained with the best electrical performance as well. The Cu/p-SiOC:H integration is thermally stable up to 500 °C due to the synergistic effect of Cu3Ge and ZrNx layers. Accordingly, the PIII process was verified in a 100-nm-thick Cu dual-damascene interconnect, in which the ZrNx diffusion barrier of 1 nm thick was successfully self-assembled on the sidewall without barrier layer on the via bottom. In this case, the via resistance was reduced by approximately 50% in comparison with Ta/TaN barrier. Considering the results in this study, ultrathin ZrNx conformal diffusion barrier can be adopted in the sub-14 nm technology node.

  4. Down-regulation of selected Blood-brain Barrier Specific Genes from Capillaries to Bovine In Vitro Models

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Brodin, Birger

    Cultures of primary bovine brain endothelial cells (BECs) grown, often together with astrocytes, on permeable supports in two-compartment culture systems are commonly used as an in vitro model of the blood-brain barrier (BBB). While trans-endothelial electrical resistance, restriction...... the in vivo gene expression of brain capillary endothelial cells. Primary bovine endothelial cells and rat astrocytes were cultured in different culture configurations and the mRNA expression of selected genes (vWF, Glut-1, P-gp, claudin-1,-5, occludin, JAM-1, LAT-1, SLC16A1, MRP-1,-4, BCRP, ZO-1, AP, TPA...

  5. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.

    Science.gov (United States)

    Kim, Seungbum; Goel, Ruby; Kumar, Ashok; Qi, Yanfei; Lobaton, Gil; Hosaka, Koji; Mohammed, Mohammed; Handberg, Eileen M; Richards, Elaine M; Pepine, Carl J; Raizada, Mohan K

    2018-03-30

    Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R 2 = 0.5301, P <0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R 2 = 0.4608, P <0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  6. IL-4 polymorphisms, HRCT score and lung tissue markers in idiopathic pulmonary fibrosis

    Czech Academy of Sciences Publication Activity Database

    Vašáková, M.; Šterclová, M.; Matěj, R.; Olejár, Tomáš; Kolesár, L.; Skibová, J.; Stříž, I.

    2013-01-01

    Roč. 74, č. 10 (2013), s. 1346-1351 ISSN 0198-8859 Institutional support: RVO:67985823 Keywords : IL-4 * gene polymorphism * idiopathic pulmonary fibrosis * PAR-2 * CD124 * TGF beta * YY-1 * TSLP Subject RIV: FC - Pulmology Impact factor: 2.282, year: 2013

  7. Barriers Approach to Innovation in Academic Libraries

    Directory of Open Access Journals (Sweden)

    Fu-Hsuan Chuang

    2016-11-01

    Full Text Available Innovation in academic libraries is not a brand new issue. Academic libraries can benefit from successful innovation, since innovation is a key contributor to gaining and sustaining competitive advantage for survival. Building on two case studies, 28 participants from leadership teams to practitioners are involved, the qualitative findings identified the specific two types of barriers that academic libraries face by applying a barriers approach to innovation, that’s, environmental and organizational barriers. Especially, seven dimensions of two types of barriers to innovation are found.

  8. Vehicle barrier with access delay

    Science.gov (United States)

    Swahlan, David J; Wilke, Jason

    2013-09-03

    An access delay vehicle barrier for stopping unauthorized entry into secure areas by a vehicle ramming attack includes access delay features for preventing and/or delaying an adversary from defeating or compromising the barrier. A horizontally deployed barrier member can include an exterior steel casing, an interior steel reinforcing member and access delay members disposed within the casing and between the casing and the interior reinforcing member. Access delay members can include wooden structural lumber, concrete and/or polymeric members that in combination with the exterior casing and interior reinforcing member act cooperatively to impair an adversarial attach by thermal, mechanical and/or explosive tools.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Xun E Zhang

    Full Text Available 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.

  11. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

    Science.gov (United States)

    Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

    2015-01-01

    The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

  12. Nuclear reorganization barriers to electron transfer

    International Nuclear Information System (INIS)

    Sutin, N.; Brunschwig, B.S.; Creutz, C.; Winkler, J.R.

    1988-01-01

    The nuclear barrier to electron transfer arises from the need for reorganization of intramolecular and solvent internuclear distances prior to electron transfer. For reactions with relatively small driving force (''normal'' free-energy region) the nuclear factors and rates increase as intrinsic inner-shell and outer-shell barriers decrease; this is illustrated by data for transition metal complexes in their ground electronic states. By contrast, in the inverted free-energy region, rates and nuclear factors decrease with decreasing ''intrinsic'' barriers; this is illustrated by data for the decay of charge-transfer excited states. Several approaches to the evaluation of the outer-shell barrier are explored in an investigation of the distance dependence of the nuclear factor in intramolecular electron-transfer processes. 39 refs., 14 figs., 3 tabs

  13. Model assessment of protective barrier designs: Part 2

    International Nuclear Information System (INIS)

    Fayer, M.J.

    1987-11-01

    Protective barriers are being considered for use at the Hanford Site to enhance the isolation of radioactive wastes from water, plant, and animal intrusion. This study assesses the effectiveness of protective barriers for isolation of wastes from water. In this report, barrier designs are reviewed and several barrier modeling assumptions are tested. 20 refs., 16 figs., 6 tabs

  14. Barriers to Mammography among Inadequately Screened Women

    Science.gov (United States)

    Stoll, Carolyn R. T.; Roberts, Summer; Cheng, Meng-Ru; Crayton, Eloise V.; Jackson, Sherrill; Politi, Mary C.

    2015-01-01

    Mammography use has increased over the past 20 years, yet more than 30% of women remain inadequately screened. Structural barriers can deter individuals from screening, however, cognitive, emotional, and communication barriers may also prevent mammography use. This study sought to identify the impact of number and type of barriers on mammography…

  15. Faculty Perceptions about Barriers to Active Learning

    Science.gov (United States)

    Michael, Joel

    2007-01-01

    Faculty may perceive many barriers to active learning in their classrooms. Four groups of participants in a faculty development workshop were asked to list their perceived barriers to active learning. Many of the problems identified were present on more than one list. The barriers fall into three categories: student characteristics, issues…

  16. Barriers to green supply chain management in Indian mining industries

    DEFF Research Database (Denmark)

    Muduli, K.; Govindan, Kannan; Barve, A.

    2013-01-01

    industries are increasingly implementing environmental management systems (EMS), cleaner production (CP), and adopting green supply chain management (GSCM) practices. GSCM focuses on a reduction of the adverse impacts of supply chain activities as well as a minimization of energy and material usage......A country's mining industry, despite its significant contributions to the country's economic growth, generally has a very poor public image because it is considered as a major environmental polluter. To acquire an improved social image, as well as to comply with government regulations, mining...... strength of the barriers will help decision makers rank them and decide a course of action that will make an optimum utilization of available resources during times of resource scarcity....

  17. Role of the blood–brain barrier in the evolution of feeding and cognition

    Science.gov (United States)

    Banks, William A

    2012-01-01

    The blood–brain barrier (BBB) regulates the blood-to-brain passage of gastrointestinal hormones, thus informing the brain about feeding and nutritional status. Disruption of this communication results in dysregulation of feeding and body weight control. Leptin, which crosses the BBB to inform the CNS about adiposity, provides an example. Impaired leptin transport, especially coupled with central resistance, results in obesity. Various substances/conditions regulate leptin BBB transport. For example, triglycerides inhibit leptin transport. This may represent an evolutionary adaptation in that hypertriglyceridemia occurs during starvation. Inhibition of leptin, an anorectic, during starvation could have survival advantages. The large number of other substances that influence feeding is explained by the complexity of feeding. This complexity includes cognitive aspects; animals in the wild are faced with cost/benefit analyses to feed in the safest, most economical way. This cognitive aspect partially explains why so many feeding substances affect neurogenesis, neuroprotection, and cognition. The relation between triglycerides and cognition may be partially mediated through triglyceride's ability to regulate the BBB transport of cognitively active gastrointestinal hormones such as leptin, insulin, and ghrelin. PMID:22612379

  18. Antimicrobial Peptides, Infections and the Skin Barrier

    DEFF Research Database (Denmark)

    Clausen, Maja Lisa; Agner, Tove

    2016-01-01

    The skin serves as a strong barrier protecting us from invading pathogens and harmful organisms. An important part of this barrier comes from antimicrobial peptides (AMPs), which are small peptides expressed abundantly in the skin. AMPs are produced in the deeper layers of the epidermis and trans......The skin serves as a strong barrier protecting us from invading pathogens and harmful organisms. An important part of this barrier comes from antimicrobial peptides (AMPs), which are small peptides expressed abundantly in the skin. AMPs are produced in the deeper layers of the epidermis...

  19. Barrier Systems

    NARCIS (Netherlands)

    Heteren, S. van

    2015-01-01

    Barrier-system dynamics are a function of antecedent topography and substrate lithology, Relative sea-level (RSL) changes, sediment availability and type, climate, vegetation type and cover, and various aero- and hydrodynamic processes during fair-weather conditions and extreme events. Global change

  20. Shakeoff Ionization near the Coulomb Barrier Energy

    Science.gov (United States)

    Sharma, Prashant; Nandi, T.

    2017-11-01

    We measure the projectile K x-ray spectra as a function of the beam energies around the Coulomb barrier in different collision systems. The energy is scanned in small steps around the barrier aiming to explore the nuclear effects on the elastically scattered projectile ions. The variation of the projectile x-ray energy with the ion-beam energies exhibits an unusual increase in between the interaction barrier and fusion barrier energies. This additional contribution to the projectile ionization can be attributed to the shakeoff of outer-shell electrons of the projectile ions due to the sudden nuclear recoil (˜10-21 sec ) caused by the attractive nuclear potential, which gets switched on near the interaction barrier energy. In the sudden approximation limit, the theoretical shakeoff probability calculation due to the nuclear recoil explains the observed data well. In addition to its fundamental interest, such processes can play a significant role in dark matter detection through the possible mechanism of x-ray emissions, where the weakly interacting massive particle-nucleus elastic scattering can lead to the nuclear-recoil-induced inner-shell vacancy creations. Furthermore, the present work may provide new prospects for atomic physics research at barrier energies as well as provide a novel technique to perform barrier distribution studies for two-body systems.

  1. Performance of Traffic Noise Barriers with Varying Cross-Section

    Directory of Open Access Journals (Sweden)

    Sanja Grubeša

    2011-05-01

    Full Text Available The efficiency of noise barriers largely depends on their geometry. In this paper, the performance of noise barriers was simulated using the numerical Boundary Element Method (BEM. Traffic noise was particularly considered with its standardized noise spectrum adapted to human hearing. The cross-section of the barriers was varied with the goal of finding the optimum shape in comparison to classical rectangular barriers. The barrier performance was calculated at different receiver points for a fixed barrier height and source position. The magnitude of the insertion loss parameter was used to evaluate the performance change, both in one-third octave bands and as the broadband mean insertion loss value. The proposed barriers of varying cross-section were also compared with a typical T-shape barrier of the same height.

  2. TIPE2 Inhibits the Expression of Asthma-Related Inflammatory Factors in Hyperstretched Bronchial Epithelial Cells Through the Wnt/β-Catenin Pathway.

    Science.gov (United States)

    Sun, Xinrong; Chen, Lu; Yan, Wen

    2017-06-01

    Childhood asthma, an airway inflammatory disease, is a serious threat to the child's quality of life. Recently, TIPE2 expression was reported to be decreased in children with asthma. Therefore, additional studies focusing on TIPE2 might provide an approach for treating childhood asthma. In this study, we found that TIPE2 was poorly expressed in hyperstretched human bronchial epithelial cells (BEAS-2B). TIPE2 overexpression also significantly suppressed the stretch-induced secretion of asthma-related inflammatory factors (TNF-α, TSLP, MMP-9, and VEGF). In contrast, TIPE2 inhibition significantly promoted the secretion of TNF-α, TSLP, MMP-9, and VEGF. Furthermore, overexpression of TIPE2 remarkably inhibited the activation of Wnt/β-catenin in hyperstretched BEAS-2B cells, while siTIPE2 activated Wnt/β-catenin in hyperstretched BEAS-2B cells. Further analysis showed that the Wnt/β-catenin signal inhibitor Dkk-1 could further enhance the TIPE2-induced suppression of Wnt/β-catenin signaling, which also suppressed the siTIPE2-induced secretion of TNF-α, TSLP, MMP-9, and VEGF in hyperstretched BEAS-2B cells. Dkk-1 reversed the effects of siRNA-TIPE2 on Wnt/β-catenin signaling and inflammatory cytokines. In summary, we have exhibited that TIPE2 inhibited the expression of asthma-related inflammatory factors in hyperstretched BEAS-2B cells by suppressing the Wnt/β-catenin signaling pathway. TIPE2 may be involved in airway inflammation during asthma attack, and it may be used as a potential therapeutic target for bronchial epithelial inflammation in childhood asthma.

  3. Resveratrol ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium

    Directory of Open Access Journals (Sweden)

    Sule Caglayan Sozmen

    2016-03-01

    Full Text Available Background. Resveratrol is a natural polyphenol that exhibits anti-inflammatory effects. The aim of this study was to investigate the effects of resveratrol treatment on epithelium-derived cytokines and epithelial apoptosis in a murine model of atopic dermatitis-like lesions. Material and Methods. Atopic dermatitis-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene to shaved dorsal skin. Twenty-one BALB/c mice were divided into three groups: group I (control, group II (vehicle control, and group III (resveratrol. Systemic resveratrol (30 mg/kg/day was administered repeatedly during the 6th week of the experiment. After the mice had been sacrificed, skin tissues were examined histologically for epithelial thickness. Epithelial apoptosis (caspase-3 and epithelium-derived cytokines [interleukin (IL-25, IL-33, and thymic stromal lymphopoietin (TSLP] were evaluated immunohistochemically. Results. Epithelial thickness and the numbers of IL-25, IL-33, TSLP and caspase-3-positive cells were significantly higher in group II compared to group I mice. There was significant improvement in epithelial thickness in group III compared with group II mice (p < 0.05. The numbers of IL-25, IL-33, and TSLP-positive cells in the epithelium were lower in group III than in group II mice (p < 0.05. The number of caspase-3-positive cells, as an indicator of apoptosis, in the epithelium was significantly lower in group III than in group II mice (p < 0.05. Conclusion. Treatment with resveratrol was effective at ameliorating histological changes and inflammation by acting on epithelium-derived cytokines and epithelial apoptosis.

  4. Removing bridge barriers stimulates suicides: an unfortunate natural experiment.

    Science.gov (United States)

    Beautrais, Annette L; Gibb, Sheree J; Fergusson, David M; Horwood, L John; Larkin, Gregory Luke

    2009-06-01

    Safety barriers to prevent suicide by jumping were removed from Grafton Bridge in Auckland, New Zealand, in 1996 after having been in place for 60 years. This study compared the number of suicides due to jumping from the bridge after the reinstallation of safety barriers in 2003. National mortality data for suicide deaths were compared for three time periods: 1991-1995 (old barrier in place); 1997-2002 (no barriers in place); 2003-2006 (after barriers were reinstated). Removal of barriers was followed by a fivefold increase in the number and rate of suicides from the bridge. These increases led to a decision to reinstall safety barriers. Since the reinstallation of barriers, of an improved design, in 2003, there have been no suicides from the bridge. This natural experiment, using a powerful a-b-a (reversal) design, shows that safety barriers are effective in preventing suicide: their removal increases suicides; their reinstatement prevents suicides.

  5. BARRIERS OF STRATEGIC ALLIANCES ORGANIZATION

    Directory of Open Access Journals (Sweden)

    Vladislav M. Sannikov

    2014-01-01

    Full Text Available General barriers of organization of different types of strategic alliances have beenconsidered in the article. There are several recommendations for overcoming themin cases of international alliances, and in case of work in one state. The article also identified goals and tasks of single coordination center of alliance to overcome organization barriers.

  6. Converse Theorems for Safety and Barrier Certificates

    OpenAIRE

    Ratschan, Stefan

    2017-01-01

    An important tool for proving safety of dynamical systems is the notion of a barrier certificate. In this paper we prove that every robustly safe ordinary differential equation has a barrier certificate. Moreover, we show a construction of such a barrier certificate based on a set of states that is reachable in finite time.

  7. Benefits of barrier fuel on fuel cycle economics

    International Nuclear Information System (INIS)

    Crowther, R.L.; Kunz, C.L.

    1988-01-01

    Barrier fuel rod cladding was developed to eliminate fuel rod failures from pellet/cladding stress/corrosion interaction and to eliminate the associated need to restrict the rate at which fuel rod power can be increased. The performance of barrier cladding has been demonstrated through extensive testing and through production application to many boiling water reactors (BWRs). Power reactor data have shown that barrier fuel rod cladding has a significant beneficial effect on plant capacity factor and plant operating costs and significantly increases fuel reliability. Independent of the fuel reliability benefit, it is less obvious that barrier fuel has a beneficial effect of fuel cycle costs, since barrier cladding is more costly to fabricate. Evaluations, measurements, and development activities, however, have shown that the fuel cycle cost benefits of barrier fuel are large. This paper is a summary of development activities that have shown that application of barrier fuel significantly reduces BWR fuel cycle costs

  8. Benchmarking the interactions among barriers in third-party logistics implementation

    DEFF Research Database (Denmark)

    Diabat, A.; Khreishah, A.; Govindan, Kannan

    2013-01-01

    Purpose: The purpose of this paper is to analyze the interaction among some of the major barriers that may hinder the implementation of third-party logistics (TPL) in manufacturing industries. Design/methodology/approach: This paper uses an interpretive structural modeling (ISM) methodology...... to analyze the interactions among the barriers. Findings: It is beneficial for the management of any firm to be aware of significant barriers and to diagnose those that could be integral to the organization's future survival. Many works have focused on identifying barriers for TPL implementation, but a model...... for such barriers is lacking. This paper attempts to develop a model for the barriers using an ISM methodology and analyzes the mutual interactions among the barriers. The model differentiates between the barriers so that driving barriers, which can intensify other barriers, and dependent barriers are identified...

  9. Highway renewable energy : photovoltaic noise barriers

    Science.gov (United States)

    2017-07-01

    Highway photovoltaic noise barriers (PVNBs) represent the combination of noise barrier systems and photovoltaic systems in order to mitigate traffic noise while simultaneously producing renewable energy. First deployed in Switzerland in 1989, PVNBs a...

  10. Some points in legal regulation of radioactive waste management

    International Nuclear Information System (INIS)

    Tikhankin, Anatoly; Levin, Alexander

    1999-01-01

    In Russia, the system of the legal acts regulating radioactive waste management is now in progress. Development of the federal norms and regulations on the use of atomic energy is a responsibility of Gosatomnazdor. This presentation describes in detail the work done by Gosatomnadzor in 1997/1998 on the development of the legal documents regulating the management of radioactive waste and spent nuclear material. A document of special importance is ''Burial of Radioactive Wastes. Principles, Criteria and Basic Safety Requirements''. This is discussed in some detail. For all stages of radioactive waste management, safety criteria for population and personnel are set up in strict analogy with current legislation for any other type of radiological hazard. A combined, or hybrid, safety criterion is suggested for estimation of long-term safety of radioactive waste repository systems, for the period upon termination of the established administrative monitoring after closing the repository. A dose criterion is accepted for normal radiation exposure and a risk criterion for potential radiation exposure. The safety of radioactive waste repository should be ensured by means of graded safeguard throughout the entire period of burial. Graded safeguard is based on independent barriers on the way of ionising radiation and emission of radioactive substances into the environment and protection and maintenance of these barriers. Examples show how the provisions of the document are applied in practice in the permafrost area of Russia. Permafrost soil has low water permeability, which is significant because underground water is the main transport medium in case of a leakage from a repository

  11. RNase L Interacts with Filamin A To Regulate Actin Dynamics and Barrier Function for Viral Entry

    Science.gov (United States)

    Siddiqui, Mohammad Adnan; Dayal, Shubham; Naji, Merna; Ezelle, Heather J.; Zeng, Chun; Zhou, Aimin; Hassel, Bret A.

    2014-01-01

    ABSTRACT The actin cytoskeleton and its network of associated proteins constitute a physical barrier that viruses must circumvent to gain entry into cells for productive infection. The mechanisms by which the physical signals of infection are sensed by the host to activate an innate immune response are not well understood. The antiviral endoribonuclease RNase L is ubiquitously expressed in a latent form and activated upon binding 2-5A, a unique oligoadenylate produced during viral infections. We provide evidence that RNase L in its inactive form interacts with the actin-binding protein Filamin A to modulate the actin cytoskeleton and inhibit virus entry. Cells lacking either RNase L or Filamin A displayed increased virus entry which was exacerbated in cells lacking both proteins. RNase L deletion mutants that reduced Filamin A interaction displayed a compromised ability to restrict virus entry, supporting the idea of an important role for the RNase L-Filamin A complex in barrier function. Remarkably, both the wild type and a catalytically inactive RNase L mutant were competent to reduce virus entry when transfected into RNase L-deficient cells, indicating that this novel function of RNase L is independent of its enzymatic activity. Virus infection and RNase L activation disrupt its association with Filamin A and release RNase L to mediate its canonical nuclease-dependent antiviral activities. The dual functions of RNase L as a constitutive component of the actin cytoskeleton and as an induced mediator of antiviral signaling and effector functions provide insights into its mechanisms of antiviral activity and opportunities for the development of novel antiviral agents. PMID:25352621

  12. Barriers to medication error reporting among hospital nurses.

    Science.gov (United States)

    Rutledge, Dana N; Retrosi, Tina; Ostrowski, Gary

    2018-03-01

    The study purpose was to report medication error reporting barriers among hospital nurses, and to determine validity and reliability of an existing medication error reporting barriers questionnaire. Hospital medication errors typically occur between ordering of a medication to its receipt by the patient with subsequent staff monitoring. To decrease medication errors, factors surrounding medication errors must be understood; this requires reporting by employees. Under-reporting can compromise patient safety by disabling improvement efforts. This 2017 descriptive study was part of a larger workforce engagement study at a faith-based Magnet ® -accredited community hospital in California (United States). Registered nurses (~1,000) were invited to participate in the online survey via email. Reported here are sample demographics (n = 357) and responses to the 20-item medication error reporting barriers questionnaire. Using factor analysis, four factors that accounted for 67.5% of the variance were extracted. These factors (subscales) were labelled Fear, Cultural Barriers, Lack of Knowledge/Feedback and Practical/Utility Barriers; each demonstrated excellent internal consistency. The medication error reporting barriers questionnaire, originally developed in long-term care, demonstrated good validity and excellent reliability among hospital nurses. Substantial proportions of American hospital nurses (11%-48%) considered specific factors as likely reporting barriers. Average scores on most barrier items were categorised "somewhat unlikely." The highest six included two barriers concerning the time-consuming nature of medication error reporting and four related to nurses' fear of repercussions. Hospitals need to determine the presence of perceived barriers among nurses using questionnaires such as the medication error reporting barriers and work to encourage better reporting. Barriers to medication error reporting make it less likely that nurses will report medication

  13. Zonulin, regulation of tight junctions, and autoimmune diseases.

    Science.gov (United States)

    Fasano, Alessio

    2012-07-01

    Recent studies indicate that besides digestion and absorption of nutrients and water and electrolytes homeostasis, another key function of the intestine is to regulate the trafficking of environmental antigens across the host mucosal barrier. Intestinal tight junctions (TJs) create gradients for the optimal absorption and transport of nutrients and control the balance between tolerance and immunity to nonself antigens. To meet diverse physiological challenges, intestinal epithelial TJs must be modified rapidly and in a coordinated fashion by regulatory systems that orchestrate the state of assembly of the TJ multiprotein network. While considerable knowledge exists about TJ ultrastructure, relatively little is known about their physiological and pathophysiological regulation. Our discovery of zonulin, the only known physiologic modulator of intercellular TJs described so far, has increased our understanding of the intricate mechanisms that regulate the intestinal epithelial paracellular pathway and has led us to appreciate that its upregulation in genetically susceptible individuals leads to autoimmune diseases. © 2012 New York Academy of Sciences.

  14. Spin-dependent dwell time through ferromagnetic graphene barrier

    International Nuclear Information System (INIS)

    Sattari, F.

    2014-01-01

    We investigated the dwell time of electrons tunneling through a ferromagnetic (FM) graphene barrier. The results show that the spin polarization can be efficiently controlled by the barrier width, barrier height, and the incident electron energy. Furthermore, it is found that electrons with different spin orientations will spend different times through the barrier. The difference of the dwell time between spin-up and spin-down electrons arises from the exchange splitting, which is induced by the FM strip. Study results indicate that a ferromagnetic graphene barrier can cause a nature spin filter mechanism in the time domain

  15. Therapeutic benefits of enhancing permeability barrier for atopic eczema

    Directory of Open Access Journals (Sweden)

    George Man

    2015-06-01

    Full Text Available The regulatory role of epidermal permeability barrier function in cutaneous inflammation has been well appreciated. While barrier disruption induces cutaneous inflammation, improvement of permeability barrier function alleviates inflammation. Studies have demonstrated that improvement of epidermal permeability barrier function not only prevents the development of atopic eczema, but also delays the relapse of these diseases. Moreover, enhancing the epidermal permeability barrier also alleviates atopic eczema. Furthermore, co-applications of barrier enhancing products with glucocorticoids can increase the therapeutic efficacy and reduce the adverse effects of glucocorticoids in the treatment of atopic eczema. Therefore, utilization of permeability barrier enhancing products alone or in combination with glucocorticoids could be a valuable approach in the treatment of atopic eczema. In this review, we discuss the benefits of improving the epidermal permeability barrier in the management of atopic eczema.

  16. Institutional Sustainability Barriers of Community Conservation Agreement as a Collaboration Management in Lore Lindu National Park

    Directory of Open Access Journals (Sweden)

    Sudirman Daeng Massiri

    2015-12-01

    Full Text Available The main problem of forest institutional arrangement is the issue of institutional sustainability in achieving sustainable forest ecosystem. This study aimed to explain the barriers of institutional sustainability Community Conservation Agreement (CCA designed in Lore Lindu National Park (LLNP, in Indonesia, as a collaborative management of national parks. This study is of descriptive which used qualitative approach, i.e. asking open-ended questions, reviewing documentation and analyzing textual of community conservation agreements. We found that the institutional sustainability barriers of CCA were the local decisions on collective-choice level and that the rules at operational level arranged in CCA were not in line with formal rules of national park management at the constitutional level. Furthermore, the low capacity of local institutions in heterogeneous villages with many migrants in controlling and regulating the forest use, especially in rehabilitation zone areas, also became a barrier to institutional sustainability of CCA. Therefore, institutional sustainability of CCA requires support of national park management policy that accommodates the sustainability of livelihoods of local communities in national parks, strengthening local institution's capacity, and ultimately integrating institution of CCA as part of LLNP management.

  17. Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

    Science.gov (United States)

    Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W; Sobrino, Agua; Hachey, Stephanie J; George, Steven C; Hughes, Christopher Cw

    2017-11-01

    The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently

  18. Should we use a direct regulation to implement the Healthy Prisons Agenda in England? A qualitative study among prison key policy makers.

    Science.gov (United States)

    Ismail, N; de Viggiani, N

    2017-08-31

    The Healthy Prisons Agenda seeks to reduce prisoners' health risks, balance prisoners' rights with a security regime, ensure equivalent prison health service provisions to community health services, and facilitate the whole-prison approach. There is an established assumption that legislation will ensure better implementation of health promotion programmes. This study aimed to examine whether a legislative framework, via a direct regulation, could lead to enhanced implementation of the Healthy Prisons Agenda in England. A qualitative study design was conducted using semi-structured interviews with 30 key prison policy makers in England. Our findings contradict the established assumption that legislation improves the implementation of health promotion programmes. A direct regulation was perceived as restrictive, manifesting excessive compliance and encouraging a risk-averse culture, whilst preoccupation with security, order and discipline amongst prison governors and custody staff was deemed an internal institutional barrier to implementing the Healthy Prisons Agenda. External barriers included diminishing resources, lengthier or delayed sentencing, and an unsympathetic public and political stance towards prisoner rehabilitation. A direct regulation should not be used to operationalize the Healthy Prisons Agenda. Rather, self-regulation, along with proactive solutions for the identified barriers to implementing the Agenda, is the most appropriate path forward. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  19. Design and installation of a strategically placed algae mesh barrier at OPG Pickering Nuclear Generating Station

    International Nuclear Information System (INIS)

    Marttila, D.; Patrick, P.; Gregoris, C.

    2009-01-01

    Ontario Power Generation's Pickering Nuclear has experienced a number of events in which attached algae have become entrained in the water intake costing approximately $30M over the 1995-2005 period as a result of deratings, Unit shutdowns and other operational issues. In 2005-2006 OPG and Kinectrics worked collaboratively on evaluating different potential solutions to reduce the impact of algae on the station. One of the solutions developed by Kinectrics included a strategically placed barrier net designed to regulate algae flow into the station intake. In 2006, Kinectrics designed and installed the system, the first of its kind at a Nuclear Power Plant in Canada. The system was operational by May 2007. OPG completed an effectiveness study in 2007 and concluded the barrier system had a beneficial effect on reducing algae impact on the station. (author)

  20. A calcite permeable reactive barrier for the remediation of Fluoride from spent potliner (SPL) contaminated groundwater

    DEFF Research Database (Denmark)

    Turner, B.D.; Binning, Philip John; Sloan, S.W.

    2008-01-01

    The use of calcite (CaCO3) as a substrate for a permeable reactive barrier (PRB) for removing fluoride from contaminated groundwater is proposed and is illustrated by application to groundwater contaminated by spent potliner leachate (SPL), a waste derived from the aluminium smelting process...... leachate indicate that the complex chemical matrix of the SPL leachate can impact fluoride removal significantly. For SPL contaminant mixtures, fluoride removal is initially less than expected from idealized, pure, solutions. However, with time, the effect of other contaminants on fluoride removal...... diminishes. Column tests also show that pH control is important for optimizing fluoride removal with the mass removed increasing with decreasing pH. Barrier pH can be regulated by CO2 addition with the point of injection being critical for optimising the remediation performance. Experimental and model...

  1. Barriers to physical activity among working mothers.

    Science.gov (United States)

    Dombrowski, Jill J

    2011-04-01

    Working mothers experience several barriers to physical activity. If these barriers can be identified by occupational health nurses and they can partner with working mothers to reduce these perceived barriers, the health of these workers can be improved and chronic disease risk prevented. The purpose of this study was to measure the effect of self-regulatory efficacy on physical activity among working mothers and to describe specific barriers to physical activity. The Barriers Specific Self-Efficacy Scale (BARSE) and the Kaiser Physical Activity Survey (KPAS) were used to measure the variables. Self-regulatory efficacy was found to be a strong predictor of physical activity in a diverse sample of working mothers who did not meet current recommendations for physical activity. Occupational health nurses can use these findings to design programs for groups and for counseling individuals. Copyright 2011, SLACK Incorporated.

  2. Barrier response to Holocene sea-level rise

    DEFF Research Database (Denmark)

    Pejrup, Morten; Andersen, Thorbjørn Joest; Johannessen, Peter N

    Normally it is believed that sea-level rise causes coastal barrier retreat. However, sea-level is only one of the parameters determining the long term coastal development of barrier coasts. Sediment supply is an equally important determinant and may overshadow the effects of sea-level rise....... Conceptually this has been known for a long time but for the first time we can show the relative effect of these two parameters. We have studied three neighboring barrier islands in the Wadden Sea, and described their 3D morphological evolution during the last 8000 years. It appears that the barrier islands...... a much stronger component of sea-level control. The distance between the islands is only 50 km, and therefore our study shows that prediction of barrier development during a period of rising sea level may be more complicated than formerly believed....

  3. Mucus as a Barrier to Drug Delivery

    DEFF Research Database (Denmark)

    Bøgh, Marie; Nielsen, Hanne Mørck

    2015-01-01

    Viscoelastic mucus lines all mucosal surfaces of the body and forms a potential barrier to mucosal drug delivery. Mucus is mainly composed of water and mucins; high-molecular weight glycoproteins forming an entangled network. Consequently, mucus forms a steric barrier and due to its negative charge...... barrier to drug delivery. Current knowledge of mucus characteristics and barrier properties, as achieved by state-of-the-art methodologies, is the topic of this MiniReview emphasizing the gastrointestinal mucus and an overall focus on oral drug delivery. Cell culture-based in vitro models are well......, studies of peptide and protein drug diffusion in and through mucus and studies of mucus-penetrating nanoparticles are included to illustrate the mucus as a potentially important barrier to obtain sufficient bioavailability of orally administered drugs, and thus an important parameter to address...

  4. Health Barriers to Learning

    Directory of Open Access Journals (Sweden)

    Delaney Gracy

    2014-01-01

    Full Text Available This article summarizes the results from a 2013 online survey with 408 principals and assistant principals in New York City public elementary and middle schools. The survey assessed three primary areas: health issues in the school, health issues perceived as barriers to learning for affected students, and resources needed to address these barriers. Eighteen of the 22 health conditions listed in the survey were considered a moderate or serious issue within their schools by at least 10% of respondents. All 22 of the health issues were perceived as a barrier to learning by between 12% and 87% of the respondents. Representatives from schools that serve a higher percentage of low-income students reported significantly higher levels of concern about the extent of health issues and their impact on learning. Respondents most often said they need linkages with organizations that can provide additional services and resources at the school, especially for mental health.

  5. Hanford prototype-barrier status report: FY 1995

    International Nuclear Information System (INIS)

    Gee, G.W.; Ward, A.L.; Gilmore, B.G.; Ligotke, M.W.; Link, S.O.

    1995-11-01

    Surface barriers (or covers) have been proposed for use at the Hanford Site as a means to isolate certain waste sites that, for reasons of cost or worker safety or both, may not be exhumed. Surface barriers are intende to isolated the wastes from the accessible environment and to provide long-term protection to future populations that might use the Hanford Site. Currently, no ''proven'' long-term barrier system is available. For this reason, the Hanford Site Permanent Isolation Surface-Barrier Development Program (BDP) was organized to develop the technology needed to provide long-term surface barrier capability for the Hanford Site for the US Department of Energy (DOE). Designs have been proposed to meet the most stringent needs for long-term waste disposal. The objective of the current barrier design is to use natural materials to develop a protective barrier system that isolates wastes for at least 1000 years by limiting water, plant, animal, and human intrusion; and minimizing erosion. The design criteria for water drainage has been set at 0.5 mm/yr. While other design criteria are more qualitative, it is clear that waste isolation for an extended time is the prime objective of the design. Constructibility and performance. are issues that can be tested and dealt with by evaluating prototype designs prior to extensive construction and deployment of covers for waste sites at Hanford

  6. Evolution of mid-Atlantic coastal and back-barrier estuary environments in response to a hurricane: Implications for barrier-estuary connectivity

    Science.gov (United States)

    Miselis, Jennifer L.; Andrews, Brian D.; Nicholson, Robert S.; Defne, Zafer; Ganju, Neil K.; Navoy, Anthony S.

    2016-01-01

    Assessments of coupled barrier island-estuary storm response are rare. Hurricane Sandy made landfall during an investigation in Barnegat Bay-Little Egg Harbor estuary that included water quality monitoring, geomorphologic characterization, and numerical modeling; this provided an opportunity to characterize the storm response of the barrier island-estuary system. Barrier island morphologic response was characterized by significant changes in shoreline position, dune elevation, and beach volume; morphologic changes within the estuary were less dramatic with a net gain of only 200,000 m3 of sediment. When observed, estuarine deposition was adjacent to the back-barrier shoreline or collocated with maximum estuary depths. Estuarine sedimentologic changes correlated well with bed shear stresses derived from numerically simulated storm conditions, suggesting that change is linked to winnowing from elevated storm-related wave-current interactions rather than deposition. Rapid storm-related changes in estuarine water level, turbidity, and salinity were coincident with minima in island and estuarine widths, which may have influenced the location of two barrier island breaches. Barrier-estuary connectivity, or the transport of sediment from barrier island to estuary, was influenced by barrier island land use and width. Coupled assessments like this one provide critical information about storm-related coastal and estuarine sediment transport that may not be evident from investigations that consider only one component of the coastal system.

  7. Nutrition-labeling regulation impacts on restaurant environments.

    Science.gov (United States)

    Saelens, Brian E; Chan, Nadine L; Krieger, James; Nelson, Young; Boles, Myde; Colburn, Trina A; Glanz, Karen; Ta, Myduc L; Bruemmer, Barbara

    2012-11-01

    Recent attempts to improve the healthfulness of away-from-home eating include regulations requiring restaurants to post nutrition information. The impact of such regulations on restaurant environments is unknown. To examine changes in restaurant environments from before to after nutrition-labeling regulation in a newly regulated county versus a nonregulated county. Using the Nutrition Environment Measures Survey-Restaurant version audit, environments within the same quick-service chain restaurants were evaluated in King County (regulated) before and 6 and 18 months after regulation enforcement and in Multnomah County (nonregulated) restaurants over a 6-month period. Data were collected in 2008-2010 and analyses conducted in 2011. Overall availability of healthy options and facilitation of healthy eating did not increase differentially in King County versus Multnomah County restaurants aside from the substantial increase in onsite nutrition information posting in King County restaurants required by the new regulation. Barriers to healthful eating decreased in King County relative to Multnomah County restaurants, particularly in food-oriented establishments. King County restaurants demonstrated modest increases in signage that promotes healthy eating, although the frequency of such promotion remained low, and the availability of reduced portions decreased in these restaurants. The healthfulness of children's menus improved modestly over time, but not differentially by county. A restaurant nutrition-labeling regulation was accompanied by some, but not uniform, improvements in other aspects of restaurant environments in the regulated compared to the nonregulated county. Additional opportunities exist for improving the healthfulness of away-from-home eating beyond menu labeling. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Near-Surface Engineered Environmental Barrier Integrity

    International Nuclear Information System (INIS)

    Piet, S.J.; Breckenridge, R.P.

    2002-01-01

    The INEEL Environmental Systems Research and Analysis (ESRA) program has launched a new R and D project on Near-Surface Engineered Environmental Barrier Integrity to increase knowledge and capabilities for using engineering and ecological components to improve the integrity of near-surface barriers used to confine contaminants from the public and the environment. The knowledge gained and the capabilities built will help verify the adequacy of past remedial decisions and enable improved solutions for future cleanup decisions. The research is planned to (a) improve the knowledge of degradation mechanisms (weathering, biological, geological, chemical, radiological, and catastrophic) in times shorter than service life, (b) improve modeling of barrier degradation dynamics, (c) develop sensor systems to identify degradation prior to failure, and (d) provide a better basis for developing and testing of new barrier systems to increase reliability and reduce the risk of failure. Our project combine s selected exploratory studies (benchtop and field scale), coupled effects accelerated aging testing and the meso-scale, testing of new monitoring concepts, and modeling of dynamic systems. The performance of evapo-transpiration, capillary, and grout-based barriers will be examined

  9. What Prevents Quality Midwifery Care? A Systematic Mapping of Barriers in Low and Middle Income Countries from the Provider Perspective.

    Directory of Open Access Journals (Sweden)

    Alex Filby

    Full Text Available Quality of care is essential for further progress in reducing maternal and newborn deaths. The integration of educated, trained, regulated and licensed midwives into the health system is associated with improved quality of care and sustained decreases in maternal and newborn mortality. To date, research on barriers to quality of care for women and newborns has not given due attention to the care provider's perspective. This paper addresses this gap by presenting the findings of a systematic mapping of the literature of the social, economic and professional barriers preventing midwifery personnel in low and middle income countries (LMICs from providing quality of care.A systematic search of five electronic databases for literature published between January 1990 and August 2013. Eligible items included published and unpublished items in all languages. Items were screened against inclusion and exclusion criteria, yielding 82 items from 34 countries. 44% discussed countries or regions in Africa, 38% in Asia, and 5% in the Americas. Nearly half the articles were published since 2011. Data was extracted and presented in a narrative synthesis and tables. Items were organized into three categories; social; economic and professional barriers, based on an analytical framework. Barriers connected to the socially and culturally constructed context of childbirth, although least reported, appear instrumental in preventing quality midwifery care.Significant social and cultural, economic and professional barriers can prevent the provision of quality midwifery care in LMICs. An analytical framework is proposed to show how the overlaps between the barriers reinforce each other, and that they arise from gender inequality. Links are made between burn out and moral distress, caused by the barriers, and poor quality care. Ongoing mechanisms to improve quality care will need to address the barriers from the midwifery provider perspective, as well as the underlying

  10. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    International Nuclear Information System (INIS)

    Cheng, Jian; Zhang, Lin; Dai, Weiqi; Mao, Yuqing; Li, Sainan; Wang, Jingjie; Li, Huanqing; Guo, Chuanyong; Fan, Xiaoming

    2015-01-01

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys 3 ]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation

  11. Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis by inhibiting the activation of nuclear factor-kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jian; Zhang, Lin [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Dai, Weiqi [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Mao, Yuqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Li, Sainan [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Wang, Jingjie; Li, Huanqing [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China); Guo, Chuanyong [Department of Gastroenterology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai (China); Fan, Xiaoming, E-mail: xiaomingfan57@sina.com [Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai (China)

    2015-02-27

    Aim: This study aimed to investigate the effect and underlying mechanism of ghrelin on intestinal barrier dysfunction in dextran sulfate sodium (DSS)-induced colitis. Methods and results: Acute colitis was induced in C57BL/6J mice by administering 2.5% DSS. Saline or 25, 125, 250 μg/kg ghrelin was administrated intraperitoneally (IP) to mice 1 day before colitis induction and on days 4, 5, and 6 after DSS administration. IP injection of a ghrelin receptor antagonist, [D-lys{sup 3}]-GHRP-6, was performed immediately prior to ghrelin injection. Ghrelin (125 or 250 μg/kg) could reduce the disease activity index, histological score, and myeloperoxidase activities in experimental colitis, and also prevented shortening of the colon. Ghrelin could prevent the reduction of transepithelial electrical resistance and tight junction expression, and bolstered tight junction structural integrity and regulated cytokine secretion. Ultimately, ghrelin inhibited nuclear factor kappa B (NF-κB), inhibitory κB-α, myosin light chain kinase, and phosphorylated myosin light chain 2 activation. Conclusions: Ghrelin prevented the breakdown of intestinal barrier function in DSS-induced colitis. The protective effects of ghrelin on intestinal barrier function were mediated by its receptor GHSR-1a. The inhibition of NF-κB activation might be part of the mechanism underlying the effects of ghrelin that protect against barrier dysfunction. - Highlights: • Ghrelin ameliorates intestinal barrier dysfunction in experimental colitis. • The effect of ghrelin is mediated by GHSR-1a. • Inhibition of NF-κB activation.

  12. Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Aschner, Michael [Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Luo, Wen-Jing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jing-Yuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2016-04-15

    As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

  13. Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

    International Nuclear Information System (INIS)

    Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua; Aschner, Michael; Luo, Wen-Jing; Chen, Jing-Yuan

    2016-01-01

    As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

  14. Markers for blood-brain barrier integrity

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld

    2015-01-01

    In recent years there has been a resurgence of interest in brain barriers and various roles their intrinsic mechanisms may play in neurological disorders. Such studies require suitable models and markers to demonstrate integrity and functional changes at the interfaces between blood, brain......, and cerebrospinal fluid. Studies of brain barrier mechanisms and measurements of plasma volume using dyes have a long-standing history, dating back to the late nineteenth-century. Their use in blood-brain barrier studies continues in spite of their known serious limitations in in vivo applications. These were well...... known when first introduced, but seem to have been forgotten since. Understanding these limitations is important because Evans blue is still the most commonly used marker of brain barrier integrity and those using it seem oblivious to problems arising from its in vivo application. The introduction...

  15. Measuring Perceived Barriers to Physical Activity in Adolescents.

    Science.gov (United States)

    Gunnell, Katie E; Brunet, Jennifer; Wing, Erin K; Bélanger, Mathieu

    2015-05-01

    Perceived barriers to moderate-to-vigorous physical activity (PA) may contribute to the low rates of moderate-to-vigorous PA in adolescents. We examined the psychometric properties of scores from the perceived barriers to moderate-to-vigorous PA scale (PB-MVPA) by examining composite reliability and validity evidence based on the internal structure of the PB-MVPA and relations with other variables. This study was a cross-sectional analysis of data collected in 2013 from adolescents (N = 507; Mage = 12.40, SD = .62) via self-report scales. Using exploratory and confirmatory factor analyses, we found that perceived barriers were best represented as two factors representing internal (e.g., "I am not interested in physical activity") and external (e.g., "I need equipment I don't have") dimensions. Composite reliability was over .80. Using multiple regression to examine the relationship between perceived barriers and moderate-to-vigorous PA, we found that perceived internal barriers were inversely related to moderate-to-vigorous PA (β = -.32, p barriers (p > .26). The PB-MVPA scale demonstrated evidence of score reliability and validity. To improve the understanding of the impact of perceived barriers on moderate-to- vigorous PA in adolescents, researchers should examine internal and external barriers separately.

  16. Hormones and the blood-brain barrier.

    Science.gov (United States)

    Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

    2015-03-01

    Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

  17. Rice Research to Break Yield Barriers

    Science.gov (United States)

    Verma, Vivek; Ramamoorthy, Rengasamy; Kohli, Ajay; Kumar, Prakash P.

    2015-10-01

    The world’s population continues to expand and it is expected to cross 9 billion by 2050. This would significantly amplify the demand for food, which will pose serious threats to global food security. Additional challenges are being imposed due to a gradual decrease in the total arable land and global environmental changes. Hence, it is of utmost importance to review and revise the existing food production strategies by incorporating novel biotechnological approaches that can help to break the crop yield barriers in the near future. In this review, we highlight some of the concerns hampering crop yield enhancements. The review also focuses on modern breeding techniques based on genomics as well as proven biotechnological approaches that enable identification and utilization of candidate genes. Another aspect of discussion is the important area of research, namely hormonal regulation of plant development, which is likely to yield valuable regulatory genes for such crop improvement efforts in the future. These strategies can serve as potential tools for developing elite crop varieties for feeding the growing billions.

  18. Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production.

    Science.gov (United States)

    Miyauchi, Eiji; O'Callaghan, John; Buttó, Ludovica F; Hurley, Gráinne; Melgar, Silvia; Tanabe, Soichi; Shanahan, Fergus; Nally, Kenneth; O'Toole, Paul W

    2012-11-01

    Enhanced barrier function is one mechanism whereby commensals and probiotic bacteria limit translocation of foreign antigens or pathogens in the gut. However, barrier protection is not exhibited by all probiotic or commensals and the strain-specific molecules involved remain to be clarified. We evaluated the effects of 33 individual Lactobacillus salivarius strains on the hydrogen peroxide (H(2)O(2))-induced barrier impairment in human epithelial Caco-2 cells. These strains showed markedly different effects on H(2)O(2)-induced reduction in transepithelial resistance (TER). The effective strains such as UCC118 and CCUG38008 attenuated H(2)O(2)-induced disassembly and relocalization of tight junction proteins, but the ineffective strain AH43324 did not. Strains UCC118 and CCUG38008 induced phosphorylation of extracellular signal-regulated kinase (ERK) in Caco-2 cells, and the ERK inhibitor U0126 attenuated the barrier-protecting effect of these strains. In contrast, the AH43324 strain induced phosphorylation of Akt and p38, which was associated with an absence of a protective effect. Global transcriptome analysis of UCC118 and AH43324 revealed that some genes in a bacteriocin gene cluster were upregulated in AH43324 under TER assay conditions. A bacteriocin-negative UCC118 mutant displayed significantly greater suppressive effect on H(2)O(2)-induced reduction in TER compared with wild-type UCC118. The wild-type strain augmented H(2)O(2)-induced phosphorylation of Akt and p38, whereas a bacteriocin-negative UCC118 mutant did not. These observations indicate that L. salivarius strains are widely divergent in their capacity for barrier protection, and this is underpinned by differences in the activation of intracellular signaling pathways. Furthermore, bacteriocin production appears to have an attenuating influence on lactobacillus-mediated barrier protection.

  19. Social Barriers to Effective Communication in Old Age

    OpenAIRE

    Anna Sanecka

    2014-01-01

    Some communication barriers apply particularly to elderly people. The social barriers to effective communication in old age are the barriers caused by stereotypes of old age/elderly people and the barriers arising from limitations in using mass communication by seniors. Stereotypes of old age/elderly people embrace views regarding old people’s communication skills and the ideas about the correct way of communication with them. Therefore the communication problems of old people are correlated ...

  20. How to break the barriers to climate awareness

    DEFF Research Database (Denmark)

    Kemp, Peter

    2016-01-01

    In this paper is provided a philosophical analysis of the cognitive barriers that may block the individual citizen’s acknowledgement of a personal responsibility to engage in climate responsible behaviour. The authors distinguish between two types of cognitive barriers; the physical barriers......, that are associated with the way we gain knowledge about climate change and the physical world state; and the psychological barriers, that arise from ideas about ourselves and the nature that surrounds us....

  1. Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood-brain barrier after CITCO activation.

    Science.gov (United States)

    Lemmen, Julia; Tozakidis, Iasson E P; Bele, Prachee; Galla, Hans-Joachim

    2013-03-21

    ATP-driven efflux transporters are considered to be the major hurdle in the treatment of central nervous system (CNS) diseases. Abcb1 (P-glycoprotein) and Abcg2 (breast cancer resistance protein/brain multidrug resistance protein) belong to the best known ABC-transporters. These ABC-transporters limit the permeability of the blood-brain barrier and protect the brain against toxic compounds in the blood but on the other hand they also reduce the efficacy of CNS pharmacotherapy. Even after 40 years of extensive research, the regulatory mechanisms of these efflux transporters are still not completely understood. To unravel the efflux transporter regulation, we analyzed the effect of the nuclear receptor CAR (constitutive androstane receptor) on the expression of Abcb1 and Abcg2 in primary cultures of porcine brain capillary endothelial cells (PBCEC). CAR is a xenobiotic-activated transcription factor, which is, like the other important nuclear receptor pregnane X receptor (PXR), highly expressed in barrier tissue and known to be a positive regulator of ABC-transporters. We demonstrate that activation of porcine CAR by the human CAR (hCAR) ligand CITCO (6-(4-chlorophenyl)-imidazo[2,1-b]thiazole-5-carbaldehyde) leads to an up-regulation of both transporters, whereas the mouse-specific CAR ligand TCPOBOP (1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene) had no effect on transporter expression. The stimulation of PBCEC with CITCO caused a significant up-regulation of both efflux-transporters on RNA-level, protein level and transport level. Furthermore the additional application of a CAR inhibitor significantly decreased the transporter expression to control niveau. In conclusion our data prove CAR activation only by the human ligand CITCO leading to an increased ABC-transporter expression and transport activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Coastal Barrier Resource Areas, Barrier Islands and Spits; s44gbb89; Barrier Beaches as defined by RI CRMC were barrier beaches as defined by RI CRMC were identified on quad maps and manually digitized from tablets, Published in 1989, 1:24000 (1in=2000ft) scale, Rhode Island and Providence Plantations.

    Data.gov (United States)

    NSGIC State | GIS Inventory — Coastal Barrier Resource Areas dataset current as of 1989. Barrier Islands and Spits; s44gbb89; Barrier Beaches as defined by RI CRMC were barrier beaches as defined...

  3. Barriers to investment in emerging power markets

    Energy Technology Data Exchange (ETDEWEB)

    Beardsworth, Jr, J J [Hunton and Williams, Richmond, VA (United States)

    1994-12-31

    Investing in private power projects in developing countries is a very different issue from investment in the US or the UK. There are many investment barriers not present in developed nations. Firstly investment barriers need to be identified. Trouble may be encountered with legal authorization; the regulatory framework; government guarantees; fuel supply security; lender protection; labour laws and local commercial restrictions such as profits repatriation, currency convertibility, and taxes. Political barriers may also be encountered in the form of: government commitments and support; funding sources; political unrest; religion; and relationships with other countries. Investment barriers may be minimised by persuading the government to remove any legal barriers; the contract has then to be agreed. Factors in a successful contract include: power purchase agreements; fuel agreements; and implementation agreements. It is vital to have a source of information on local rules and customs, by working with local companies and employing local attorneys.

  4. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications.

    Science.gov (United States)

    Fasano, Alessio

    2012-10-01

    One of the most important and overlooked functions of the gastrointestinal tract is to provide a dynamic barrier to tightly controlled antigen trafficking through both the transcellular and paracellular pathways. Intercellular tight junctions (TJ) are the key structures regulating paracellular trafficking of macromolecules. Although steady progress has been made in understanding TJ ultrastructure, relatively little is known about their pathophysiological regulation. Our discovery of zonulin, the only known physiological modulator of intercellular TJ described so far, increased understanding of the intricate mechanisms that regulate gut permeability and led us to appreciate that its up-regulation in genetically susceptible individuals may lead to immune-mediated diseases. This information has translational implications, because the zonulin pathway is currently exploited to develop both diagnostic and therapeutic applications pertinent to a variety of immune-mediated diseases. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Tree-inception in PMMA with a barrier

    International Nuclear Information System (INIS)

    Gefle, O S; Lebedev, S M; Pokholkov, Y P; Gockenbach, E; Borsi, H

    2004-01-01

    The experimental results of a study of the tree-inception phenomenon for three-layer dielectrics in a divergent field are presented in this paper. It is shown that the tree-inception time depends on both the position of the high-permittivity barrier in the insulating gap and the ratio of the permittivities of the barrier material and main dielectric, and that it has a maximum at the optimal barrier position. It is found that the tree-inception length has a minimum value at this barrier position. Good agreement between the coefficient of the local field non-uniformity and the tree-inception time or the initial tree length was found

  6. Quasi-relativistic effects in barrier-penetration processes

    International Nuclear Information System (INIS)

    Anchishkin, D.V.

    1991-01-01

    The problem of a particle tunneling through the potential barrier is solved within quasi-relativistic Schroedinger equation. It is shown that the subbarrier relativistic effects give a significant addition to penetration coefficient when some relations between parameters of the barrier and mass of a tunneling particle are satisfied. For instance an account of these effects for penetration of low energy π + -mesons through Coulomb barrier of the 298 U nuclei would give the increasing of penetration coefficient to 30 percent as compared to the nonrelativistic one. Also we give the criteria under which the contribution of the ''under barrier relativism'' to penetration coefficient becomes essential. 3 refs.; 6 figs. (author)

  7. In the interest of food safety: a qualitative study investigating communication and trust between food regulators and food industry in the UK, Australia and New Zealand

    Directory of Open Access Journals (Sweden)

    Samantha B Meyer

    2017-02-01

    Full Text Available Abstract Background Food regulatory bodies play an important role in public health, and in reducing the costs of food borne illness that are absorbed by both industry and government. Regulation in the food industry involves a relationship between regulators and members of the industry, and it is imperative that these relationships are built on trust. Research has shown in a variety of contexts that businesses find the most success when there are high levels of trust between them and their key stakeholders. An evidence-based understanding of the barriers to communication and trust is imperative if we are to put forward recommendations for facilitating the (rebuilding of trusting and communicative relationships. Methods We present data from 72 interviews with regulators and industry representatives regarding their trust in and communication with one another. Interviews were conducted in the UK, New Zealand, and Australia in 2013. Results Data identify a variety of factors that shape the dynamic and complex relationships between regulators and industry, as well as barriers to communication and trust between the two parties. Novel in our approach is our emphasis on identifying solutions to these barriers from the voices of industry and regulators. Conclusions We provide recommendations (e.g., development of industry advisory boards to facilitate the (rebuilding of trusting and communicative relationships between the two parties.

  8. The development, regulation and use of biopesticides for integrated pest management

    Science.gov (United States)

    Chandler, David; Bailey, Alastair S.; Tatchell, G. Mark; Davidson, Gill; Greaves, Justin; Grant, Wyn P.

    2011-01-01

    Over the past 50 years, crop protection has relied heavily on synthetic chemical pesticides, but their availability is now declining as a result of new legislation and the evolution of resistance in pest populations. Therefore, alternative pest management tactics are needed. Biopesticides are pest management agents based on living micro-organisms or natural products. They have proven potential for pest management and they are being used across the world. However, they are regulated by systems designed originally for chemical pesticides that have created market entry barriers by imposing burdensome costs on the biopesticide industry. There are also significant technical barriers to making biopesticides more effective. In the European Union, a greater emphasis on Integrated Pest Management (IPM) as part of agricultural policy may lead to innovations in the way that biopesticides are regulated. There are also new opportunities for developing biopesticides in IPM by combining ecological science with post-genomics technologies. The new biopesticide products that will result from this research will bring with them new regulatory and economic challenges that must be addressed through joint working between social and natural scientists, policy makers and industry. PMID:21624919

  9. Efficiency analysis of energy networks: An international survey of regulators

    International Nuclear Information System (INIS)

    Haney, Aoife Brophy; Pollitt, Michael G.

    2009-01-01

    Incentive regulation for networks has been an important part of the reform agenda in a number of countries. As part of this regulatory process, incentives are put in place to improve the cost efficiency of network companies by rewarding good performance relative to a pre-defined benchmark. The techniques used to establish benchmarks are central to the efficiency improvements that are ultimately achieved. Much experience has been gained internationally in the application of benchmarking techniques and we now have a solid understanding of the main indicators of best practice. What we are lacking is a more complete understanding of the factors that influence choice of methods by regulators. In this paper, we present the results of an international survey of energy regulators in 40 countries conducted electronically between June and October 2008. Regulators from European, Australasian and Latin American countries are represented in the survey. Our results show that benchmarking techniques are now widespread in the regulation of gas and electricity networks. Best practice, however, is limited to a small number of regulators. We conclude by summarising existing trends and offering some recommendations on overcoming barriers to best practice efficiency analysis.

  10. Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood-brain barrier and blood-spinal cord barrier.

    Science.gov (United States)

    Watson, P Marc D; Paterson, Judy C; Thom, George; Ginman, Ulrika; Lundquist, Stefan; Webster, Carl I

    2013-06-18

    Modelling the blood-CNS barriers of the brain and spinal cord in vitro continues to provide a considerable challenge for research studying the passage of large and small molecules in and out of the central nervous system, both within the context of basic biology and for pharmaceutical drug discovery. Although there has been considerable success over the previous two decades in establishing useful in vitro primary endothelial cell cultures from the blood-CNS barriers, no model fully mimics the high electrical resistance, low paracellular permeability and selective influx/efflux characteristics of the in vivo situation. Furthermore, such primary-derived cultures are typically labour-intensive and generate low yields of cells, limiting scope for experimental work. We thus aimed to establish protocols for the high yield isolation and culture of endothelial cells from both rat brain and spinal cord. Our aim was to optimise in vitro conditions for inducing phenotypic characteristics in these cells that were reminiscent of the in vivo situation, such that they developed into tight endothelial barriers suitable for performing investigative biology and permeability studies. Brain and spinal cord tissue was taken from the same rats and used to specifically isolate endothelial cells to reconstitute as in vitro blood-CNS barrier models. Isolated endothelial cells were cultured to expand the cellular yield and then passaged onto cell culture inserts for further investigation. Cell culture conditions were optimised using commercially available reagents and the resulting barrier-forming endothelial monolayers were characterised by functional permeability experiments and in vitro phenotyping by immunocytochemistry and western blotting. Using a combination of modified handling techniques and cell culture conditions, we have established and optimised a protocol for the in vitro culture of brain and, for the first time in rat, spinal cord endothelial cells. High yields of both CNS

  11. Use of electrical barriers to deter movement of round goby

    Science.gov (United States)

    Savino, Jacqueline F.; Jude, David J.; Kostich, Melissa J.; Coutant, Charles C.

    2001-01-01

    An electrical barrier was chosen as a possible means to deter movement of round goby Neogobius melanostomus. Feasibility studies in a 2.1-m donut-shaped tank determined the electrical parameters necessary to inhibit round goby from crossing the 1-m stretch of the benthic, electrical barrier. Increasing electrical pulse duration and voltage increased effectiveness of the barrier in deterring round goby movement through the barrier. Differences in activity of round goby during daytime and nocturnal tests did not change the effectiveness of the barrier. In field verification studies, an electrical barrier was placed between two blocking nets in the Shiawassee River, Michigan. The barrier consisted of a 6-m wide canvas on which were laid four cables carrying the electrical current. Seven experiments were conducted, wherein 25 latex paint-marked round goby were introduced upstream of the electrical barrier and recovered 24 h later upstream, on, and downstream of the barrier. During control studies, round goby moved across the barrier within 20 min from release upstream. With the barrier on and using the prescribed electrical settings shown to inhibit passage in the laboratory, the only marked round goby found below the barrier were dead. At reduced pulse durations, a few round goby (mean one/test) were found alive, but debilitated, below the barrier. The electrical barrier could be incorporated as part of a program in reducing movement of adult round goby through artificial connections between watersheds.

  12. Impedance-based cell monitoring: barrier properties and beyond

    Directory of Open Access Journals (Sweden)

    Benson Kathrin

    2013-01-01

    Full Text Available Abstract In multicellular organisms epithelial and endothelial cells form selective permeable interfaces between tissue compartments of different chemical compositions. Tight junctions which connect adjacent cells, control the passage of molecules across the barrier and, in addition, facilitate active transport processes. The cellular barriers are not static but can be deliberately modulated by exposure to specific external stimuli. In vitro models representing the essential absorption barriers of the body are nowadays available, thus allowing investigation of the parameters that control permeability as well as transport processes across those barriers. Independent of the origin of the barrier forming cells, techniques are needed to quantify their barrier integrity. One simple assay is to measure the permeability for given hydrophilic substrates possessing different molecular weights like sucrose or dextrans. However, this technique is time-consuming and labor-intensive. Moreover, radioactive or fluorescently-labeled substrates are needed to allow easy analytical detection. Finally, if transport processes are investigated, the standard permeant may interfere with the transport process under investigation or might even alter the barrier integrity by itself. Thus, independent, non-invasive techniques are needed to quantify the barrier integrity continuously during the experiment. Such techniques are available and are mainly based on the measurement of the transendothelial or transepithelial electrical resistance (TEER of barrier forming cells grown on porous membranes. Simple devices using two sets of electrodes (so-called Voltohmeters are widely used. In addition, an easy-to-use physical technique called impedance spectroscopy allows the continuous analysis of both the TEER and the electrical capacitance giving additional information about the barrier properties of cells grown on permeable membranes. This technique is useful as a quality control

  13. SOME OBSERVATIONS ON THE DESIGN OF NOISE BARRIERS

    Directory of Open Access Journals (Sweden)

    Arkadiusz BOCZKOWSKI

    2013-04-01

    Full Text Available The issue connected with effectiveness of noise barriers has been the subject of numerous considerations among acousticians. On the one hand, noise barriers are still the most popular and the most frequently used protection against traffic noise, on the other hand, however, the excessive number of noise barriers and the results of research focusing on effectiveness of the existing barriers make us reflect whether it is reasonable to use them. Very often low effectiveness of noise barriers is related to a badly conducted designing process. This article presents the basic mistakes made by noise barriers’ designers and the consequences thereof. Next, the paper describes the appropriate approach to the process of the noise barriers’ design which consists in the use of computer methods and conducting of a detailed analysis of the acoustic field’s distribution both behind the barrier and on the facades of the acoustically protected buildings.

  14. Concrete road barriers subjected to impact loads: An overview

    Directory of Open Access Journals (Sweden)

    Muhammad Fauzi Bin Mohd. Zain

    Full Text Available Abstract Concrete barriers prevent vehicles from entering the opposite lane and going off the road. An important factor in the design of concrete barriers is impact load, which a vehicle exerts upon collision with a concrete barrier. This study suggests that a height of 813 mm, a base width of 600 mm, and a top width of 240 mm are optimum dimensions for a concrete barrier. These dimensions ensure the stability of concrete barriers during vehicle collisions. An analytical and experimental model is used to analyze the concrete barrier design. The LS-DYNA software is utilized to create the analytical models because it can effectively simulate vehicle impact on concrete barriers. Field tests are conducted with a vehicle, whereas laboratory tests are conducted with machines that simulate collisions. Full-scale tests allow the actual simulation of vehicle collisions with concrete barriers. In the vehicle tests, a collision angle of 25°, collision speeds of 100 km per hour, and a vehicle weighing more than 2 t are considered in the reviewed studies. Laboratory tests are performed to test bridge concrete barriers in static condition.

  15. Thymic stromal lymphopoietin as a novel mediator amplifying immunopathology in rheumatic disease

    NARCIS (Netherlands)

    Hillen, Maarten R.; Radstake, Timothy R. D. J.; Hack, Cornelis E.; van Roon, Joel A. G.

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) is an IL-7-related cytokine that has been studied extensively in atopic diseases and more recently in various rheumatic disorders. It is involved in T cell development in the thymus and promotes homeostatic T cell expansion by classical dendritic cells. However,

  16. PRIORITISING LEAN CONSTRUCTION BARRIERS IN UGANDA'S CONSTRUCTION INDUSTRY

    Directory of Open Access Journals (Sweden)

    Henry Mwanaki Alinaitwe

    2009-06-01

    Full Text Available Engaging in lean construction efforts could prove to be highly rewarding for building firms in Uganda. However, lean construction is risky and can be disastrous if not properly managed. Lean production efforts in some other countries have not been successful due to the many barriers to its successful implementation. To enable sound lean construction efforts and to increase the chances of success in eliminating waste, a thorough investigation of the barriers is essential. This study presents 31 barriers and investigates their influence (strength on the success of lean construction initiatives. Structured interviews were carried out with technical managers of building firms to assess their perception of the barriers to lean production based on their experience at their firms. The strongest barrier is the provision of inputs exactly when required. Additionally, the barriers were ranked according to the ease of overcoming each. The easiest barrier to overcome is keeping the required items in the right place. Finally, a graphical aid is provided to enable decision makers to concentrate their efforts on the influential (strong, yet easy to overcome barriers. A lack of buildable designs and a participative management style for the workforce are the most important barriers to successful waste reduction in terms of strength and ease of overcoming. On the other hand, a lack of an organisational culture that supports teamwork, a lack of prefabrication and a lack of knowledgeable and skilled workers are regarded as low in strength, and at the same time difficult to overcome.

  17. Collective Phenomena In Volume And Surface Barrier Discharges

    Science.gov (United States)

    Kogelschatz, U.

    2010-07-01

    Barrier discharges are increasingly used as a cost-effective means to produce non-equilibrium plasmas at atmospheric pressure. This way, copious amounts of electrons, ions, free radicals and excited species can be generated without appreciable gas heating. In most applications the barrier is made of dielectric material. In laboratory experiments also the use of resistive, ferroelectric and semiconducting materials has been investigated, also porous ceramic layers and dielectric barriers with controlled surface conductivity. Major applications utilizing mainly dielectric barriers include ozone generation, surface cleaning and modification, polymer and textile treatment, sterilization, pollution control, CO2 lasers, excimer lamps, plasma display panels (flat TV screens). More recent research efforts are also devoted to biomedical applications and to plasma actuators for flow control. Sinu- soidal feeding voltages at various frequencies as well as pulsed excitation schemes are used. Volume as well as surface barrier discharges can exist in the form of filamentary, regularly patterned or laterally homogeneous discharges. Reviews of the subject and the older literature on barrier discharges were published by Kogelschatz (2002, 2003), by Wagner et al. (2003) and by Fridman et al. (2005). A detailed discussion of various properties of barrier discharges can also be found in the recent book "Non-Equilibrium Air Plasmas at Atmospheric Pressure" by Becker et al. (2005). The physical effects leading to collective phenomena in volume and surface barrier discharges will be discussed in detail. Special attention will be given to self-organization of current filaments. Main similarities and differences of the two types of barrier discharges will be elaborated.

  18. Barriers to Participation in Parenting Programs: The Relationship between Parenting Stress, Perceived Barriers, and Program Completion.

    Science.gov (United States)

    Rostad, Whitney L; Moreland, Angela D; Valle, Linda Anne; Chaffin, Mark J

    2018-04-01

    Families experiencing child maltreatment or risk factors for child maltreatment often receive referrals to interventions focused on changing parenting practices. Compliance with specific parenting programs can be challenging as many of the stressors that place families at-risk may also interfere with program participation. Because families may receive limited benefit from programs they do not fully receive, it is critical to understand the relationship between parenting stress and barriers to program completion. We used structural equation modeling to examine the relationship among parenting stress, perceived barriers to program participation, and program completion in two datasets involving low-income parents. Data were collected at two time points from a sample of parents involved with child welfare services and a sample of parents considered at-risk of future involvement (total study n = 803). Direct paths from parenting stress at time 1 to barriers to participation and parenting stress at time 2, and from parenting stress at time 2 to program completion were significant. Interestingly, increased barriers to participation were related to increased parenting stress at time 2, and greater parenting stress was related to increased program completion. Results suggest that with increasing levels of parenting stress, parents have an increased likelihood of completing the program. Assessing and addressing the influence of perceived barriers and parenting stress on program participation may decrease the likelihood of treatment attrition.

  19. Single-electron tunneling in double-barrier nanostructures

    International Nuclear Information System (INIS)

    Goldman, V.J.; Su, B.; Cunningham, J.E.

    1992-01-01

    In this paper, the authors review experimental study of charge transport in nanometer double-barrier resonant tunneling devices. Heterostructure material is asymmetric: one barrier is substantially less transparent than the other. Resonant tunneling through size-quantized well states and single-electron charging of the well are thus largely separated in the two bias polarities. When the emitter barrier is more transparent than the collector barrier, electrons accumulate in the well; incremental electron occupation of the well is accompanied by Coulomb blockade leading to sharp steps of the tunneling current. When the emitter barrier is less transparent, the current reflects resonant tunneling of just one electron at a time through size-quantized well states; the current peaks and/or steps (depending on experimental parameters) appear in current-voltage characteristics. Magnetic field and temperature effects are also reviewed. Good agreement is achieved in comparison of many features of experimental data with simple theoretical models

  20. SME's perceptions regarding strategic and structural entry barriers

    NARCIS (Netherlands)

    Lutz, Clemens; Kemp, Ron; Dijkstra, S. Gerhard

    2007-01-01

    Abstract Extant literature discusses a large number of different entry barriers that may hamper market efficiency or entrepreneurial activity. In practice several of these barriers cohere and stem from the same root. Factor analysis is used to identify the underlying dimensions of these barriers. 7

  1. An oncological view on the blood-testis barrier

    NARCIS (Netherlands)

    Bart, J; Groen, HJM; van der Graaf, WTA; Hollema, H; Hendrikse, NH; Vaalburg, W; Sleijfer, DT; de Vries, EGE

    The function of the blood-testis barrier is to protect germ cells from harmful influences; thus, it also impedes the delivery of chemotherapeutic drugs to the testis. The barrier has three components: first, a physicochemical barrier consisting of continuous capillaries, Sertoli cells in the tubular

  2. Recombination at DNA replication fork barriers is not universal and is differentially regulated by Swi1.

    Science.gov (United States)

    Pryce, David W; Ramayah, Soshila; Jaendling, Alessa; McFarlane, Ramsay J

    2009-03-24

    DNA replication stress has been implicated in the etiology of genetic diseases, including cancers. It has been proposed that genomic sites that inhibit or slow DNA replication fork progression possess recombination hotspot activity and can form potential fragile sites. Here we used the fission yeast, Schizosaccharomyces pombe, to demonstrate that hotspot activity is not a universal feature of replication fork barriers (RFBs), and we propose that most sites within the genome that form RFBs do not have recombination hotspot activity under nonstressed conditions. We further demonstrate that Swi1, the TIMELESS homologue, differentially controls the recombination potential of RFBs, switching between being a suppressor and an activator of recombination in a site-specific fashion.

  3. Patients' reports of barriers to expressing concerns during cancer consultations.

    Science.gov (United States)

    Brandes, Kim; Linn, Annemiek J; Smit, Edith G; van Weert, Julia C M

    2015-03-01

    To identify cancer patients' most influential barriers to expressing concerns during cancer consultations in a new manner by examining patients' reports of perceived barriers and perceived occurrence of barriers in consultations. Two online focus groups (N=16) and an online survey (N=236) were conducted among cancer patients and cancer survivors. The online focus groups and survey were used to examine two elements of patients' barriers, i.e., patients' reports of perceived barriers and perceived occurrence of barriers in consultations. Composite scores of these two elements were calculated to determine influential barriers. Results showed that the most influential barriers were related to providers' behavior (e.g., providers do not explicitly invite patients to express concerns) and the environment where the consultation takes place (e.g., perceived lack of time). The results of this study indicate that influential barriers to expressing concerns are barriers that patients cannot overcome themselves (i.e., they are related to providers' behavior or the environment of the consultation). A collaborative approach between researchers, providers and policy makers is needed to overcome these barriers. The results of this study can be used to develop strategies to overcome barriers to patients expressing concerns. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Barriers to adherence in cystic fibrosis

    DEFF Research Database (Denmark)

    Bregnballe, Vibeke; Schiøtz, Peter Oluf

    2012-01-01

    Danish patients with cystic fibrosis aged 14 to 25 years and their parents. Conclusions: The present study showed that the majority of adolescents with CF and their parents experienced barriers to treatment adherence. Patients and parents agreed that the three most common barriers encountered lack...

  5. Automated Impedance Tomography for Monitoring Permeable Reactive Barrier Health

    Energy Technology Data Exchange (ETDEWEB)

    LaBrecque, D J; Adkins, P L

    2009-07-02

    The objective of this research was the development of an autonomous, automated electrical geophysical monitoring system which allows for near real-time assessment of Permeable Reactive Barrier (PRB) health and aging and which provides this assessment through a web-based interface to site operators, owners and regulatory agencies. Field studies were performed at four existing PRB sites; (1) a uranium tailing site near Monticello, Utah, (2) the DOE complex at Kansas City, Missouri, (3) the Denver Federal Center in Denver, Colorado and (4) the Asarco Smelter site in East Helena, Montana. Preliminary surface data over the PRB sites were collected (in December, 2005). After the initial round of data collection, the plan was modified to include studies inside the barriers in order to better understand barrier aging processes. In September 2006 an autonomous data collection system was designed and installed at the EPA PRB and the electrode setups in the barrier were revised and three new vertical electrode arrays were placed in dedicated boreholes which were in direct contact with the PRB material. Final data were collected at the Kansas City, Denver and Monticello, Utah PRB sites in the fall of 2007. At the Asarco Smelter site in East Helena, Montana, nearly continuous data was collected by the autonomous monitoring system from June 2006 to November 2007. This data provided us with a picture of the evolution of the barrier, enabling us to examine barrier changes more precisely and determine whether these changes are due to installation issues or are normal barrier aging. Two rounds of laboratory experiments were carried out during the project. We conducted column experiments to investigate the effect of mineralogy on the electrical signatures resulting from iron corrosion and mineral precipitation in zero valent iron (ZVI) columns. In the second round of laboratory experiments we observed the electrical response from simulation of actual field PRBs at two sites: the

  6. Circularly polarized antennas for active holographic imaging through barriers

    Science.gov (United States)

    McMakin, Douglas L [Richland, WA; Severtsen, Ronald H [Richland, WA; Lechelt, Wayne M [West Richland, WA; Prince, James M [Kennewick, WA

    2011-07-26

    Circularly-polarized antennas and their methods of use for active holographic imaging through barriers. The antennas are dielectrically loaded to optimally match the dielectric constant of the barrier through which images are to be produced. The dielectric loading helps to remove barrier-front surface reflections and to couple electromagnetic energy into the barrier.

  7. Information barriers for the protection of sensitive information

    International Nuclear Information System (INIS)

    Dougan, A.D.; Dunn, J.; Seager, K.; Smith, M.; Beach, D.; Clinton, J.; Vanier, P.

    2013-01-01

    An Information Barrier is a combination of technology and procedures that prevent the release of a host country's sensitive information to a monitoring party during an inspection of a sensitive item, while enabling assurance of an accurate assessment of host country declarations regarding the item. Information barriers, as a concept, arose from the need to balance two competing requirements - specifically, certification of information protection by a host country and authentication of measurement and information accuracy by a monitoring party. The U.S. Department of Energy's National Nuclear Security Administration, in conjunction with several U.S. National Laboratories, has explored information barrier development in detail, and has continued the evolution of essential work done by the U.S. Information Barrier Working Group beginning in the late 1990's, and other international efforts, including the U.S.-Russia-IAEA Trilateral Initiative. This paper explains the rationale for information barriers, and explores the development and application of information barrier concepts for potential future arms control initiatives, including recent work and advances in capabilities. It also considers applications of information barrier concepts applied in other fields.The paper is followed by the slides of the presentation. (authors)

  8. Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

    Science.gov (United States)

    Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

    2013-01-01

    The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg−1·day−1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux. PMID:23639809

  9. Theoretical analysis of the rotational barrier of ethane.

    Science.gov (United States)

    Mo, Yirong; Gao, Jiali

    2007-02-01

    The understanding of the ethane rotation barrier is fundamental for structural theory and the conformational analysis of organic molecules and requires a consistent theoretical model to differentiate the steric and hyperconjugation effects. Due to recently renewed controversies over the barrier's origin, we developed a computational approach to probe the rotation barriers of ethane and its congeners in terms of steric repulsion, hyperconjugative interaction, and electronic and geometric relaxations. Our study reinstated that the conventional steric repulsion overwhelmingly dominates the barriers.

  10. Visual selective attention with virtual barriers.

    Science.gov (United States)

    Schneider, Darryl W

    2017-07-01

    Previous studies have shown that interference effects in the flanker task are reduced when physical barriers (e.g., hands) are placed around rather than below a target flanked by distractors. One explanation of this finding is the referential coding hypothesis, whereby the barriers serve as reference objects for allocating attention. In five experiments, the generality of the referential coding hypothesis was tested by investigating whether interference effects are modulated by the placement of virtual barriers (e.g., parentheses). Modulation of flanker interference was found only when target and distractors differed in size and the virtual barriers were beveled wood-grain objects. Under these conditions and those of previous studies, the author conjectures that an impression of depth was produced when the barriers were around the target, such that the target was perceived to be on a different depth plane than the distractors. Perception of depth in the stimulus display might have led to referential coding of the stimuli in three-dimensional (3-D) space, influencing the allocation of attention beyond the horizontal and vertical dimensions. This 3-D referential coding hypothesis is consistent with research on selective attention in 3-D space that shows flanker interference is reduced when target and distractors are separated in depth.

  11. Electron tunneling across a tunable potential barrier

    International Nuclear Information System (INIS)

    Mangin, A; Anthore, A; Rocca, M L Della; Boulat, E; Lafarge, P

    2009-01-01

    We present an experiment where the elementary quantum electron tunneling process should be affected by an independent gate voltage parameter. We have realized nanotransistors where the source and drain electrodes are created by electromigration inducing a nanometer sized gap acting as a tunnel barrier. The barrier potential shape is in first approximation considered trapezoidal. The application of a voltage to the gate electrode close to the barrier region can in principle affect the barrier shape. Simulations of the source drain tunnel current as a function of the gate voltage predict modulations as large as one hundred percent. The difficulty of observing the predicted behaviour in our samples might be due to the peculiar geometry of the realized tunnel junction.

  12. Improving access to new diagnostics through harmonised regulation: priorities for action

    Directory of Open Access Journals (Sweden)

    Ruth McNerney

    2014-04-01

    Full Text Available A new generation of diagnostic tests is being developed for use at the point of care that could save lives and reduce the spread of infectious diseases through early detection and treatment. It is important that patients in developing countries have access to these products at affordable prices and without delay. Regulation of medical products is intended to ensure safety and quality whilst balancing the need for timely access to beneficial new products. Current regulatory oversight of diagnostic tests in developing countries is highly variable and weak regulation allows poor-quality tests to enter the market. However, inefficient orover zealous regulation results in unnecessary delays, increases costs and acts as a barrier to innovation and market entry. Setting international standards and streamlining the regulatory process could reduce these barriers. Four priority activities have been identified where convergence of standards and protocols or joint review of data would be advantageous: (1 adoption of a common registration file for pre-market approval; (2 convergence of quality standards for manufacturing site inspections; (3 use of common evaluation protocols, aswell as joint review of data, to reduce unnecessary duplication of lengthy and costly clinical performance studies; and (4 use of networks of laboratories for post-market surveillance in order to monitor ongoing quality of diagnostic devices. The adoption and implementation of such measures in developing countries could accelerate access to new diagnostic tests that are safe and affordable.

  13. Improving access to new diagnostics through harmonised regulation: priorities for action.

    Science.gov (United States)

    McNerney, Ruth; Sollis, Kimberly; Peeling, Rosanna W

    2014-01-01

    A new generation of diagnostic tests is being developed for use at the point of care that could save lives and reduce the spread of infectious diseases through early detection and treatment. It is important that patients in developing countries have access to these products at affordable prices and without delay. Regulation of medical products is intended to ensure safety and quality whilst balancing the need for timely access to beneficial new products. Current regulatory oversight of diagnostic tests in developing countries is highly variable and weak regulation allows poor-quality tests to enter the market. However, inefficient or overzealous regulation results in unnecessary delays, increases costs and acts as a barrier to innovation and market entry. Setting international standards and streamlining the regulatory process could reduce these barriers. Four priority activities have been identified where convergence of standards and protocols or joint review of data would be advantageous: (1) adoption of a common registration file for pre-market approval; (2) convergence of quality standards for manufacturing site inspections; (3) use of common evaluation protocols, as well as joint review of data, to reduce unnecessary duplication of lengthy and costly clinical performance studies; and (4) use of networks of laboratories for post-market surveillance in order to monitor ongoing quality of diagnostic devices. The adoption and implementation of such measures in developing countries could accelerate access to new diagnostic tests that are safe and affordable.

  14. Patient-related barriers to pain management: the Barriers Questionnaire II (BQ-II).

    Science.gov (United States)

    Gunnarsdottir, Sigridur; Donovan, Heidi S; Serlin, Ronald C; Voge, Catherine; Ward, Sandra

    2002-10-01

    Patients' beliefs can act as barriers to optimal management of cancer pain. The Barriers Questionnaire (BQ) is a tool used to evaluate such barriers. Here, the BQ has been revised to reflect changes in pain management practices, resulting in the Barriers Questionnaire-II (BQ-II), a 27-item, self report instrument. This paper presents the results from two studies where the psychometric properties of the BQ-II were evaluated. In the first study, the responses of 27 nurses trained in pain management were compared to responses of a convenience sample of 12 patients with cancer. The results indicated that patients with cancer had higher mean scores on the BQ-II than did nurses trained in pain management. In the second study, a convenience sample of 172 patients with cancer responded to the BQ-II and a set of pain and quality of life (QOL) measures. A factor analysis supported four factors. Factor one, physiological effects, consists of 12 items addressing the beliefs that side effects of analgesics are inevitable and unmanageable, concerns about tolerance, and concerns about not being able to monitor changes in one's body when taking strong pain medications. Factor two, Fatalism, consists of three items addressing fatalistic beliefs about cancer pain and its management. Factor three, Communication, consists of six items addressing the concern that reports of pain distract the physician from treating the underlying disease, and the belief that 'good' patients do not complain of pain. The fourth and final factor, harmful effects, consists of six items addressing fear of becoming addicted to pain medication and the belief that pain medications harm the immune system. The BQ-II total had an internal consistency of 0.89, and alpha for the subscales ranged from 0.75 to 0.85. Mean (SD) scores on the total scale was 1.52 (0.73). BQ-II scores were related to measures of pain intensity and duration, mood, and QOL. Patients who used adequate analgesics for their levels of pain had

  15. Partitioning of methyl internal rotational barrier energy of ...

    Indian Academy of Sciences (India)

    The nature of methyl internal rotational barrier in thioacetaldehyde has been investigated by relaxation effect, natural bond orbital (NBO) analysis and Pauling exchange interactions. The true experimental barrier can be obtained by considering fully relaxed rotation. Nuclear-electron attraction term is a barrier forming term in ...

  16. Microscopic study on dynamic barrier in fusion reactions

    International Nuclear Information System (INIS)

    Wu Xizhen; Tian Junlong; Zhao Kai; Li Zhuxia; Wang Ning

    2004-01-01

    The authors briefly review the fusion process of very heavy nuclear systems and some theoretical models. The authors propose a microscopic transport dynamic model, i.e. the Improved Quantum Molecular Dynamic model, for describing fusion reactions of heavy systems, in which the dynamical behavior of the fusion barrier in heavy fusion systems has been studied firstly. The authors find that with the incident energy decreasing the lowest dynamic barrier is obtained which approaches to the adiabatic static barrier and with increase of the incident energy the dynamic barrier goes up to the diabatic static barrier. The authors also indicate that how the dynamical fusion barrier is correlated with the development of the configuration of fusion partners along the fusion path. Associating the single-particle potentials obtained at different stages of fusion with the Two Center Shell Model, authors can study the time evolution of the single particle states of fusion system in configuration space of single particle orbits along the fusion path. (author)

  17. Recent results from TMX-U thermal barrier experiments

    International Nuclear Information System (INIS)

    Molvik, A.W.; Allen, S.; Barter, J.

    1984-01-01

    The Tandem Mirror Experiment-Upgrade (TMX-U) device was designed to study plasma confinement in a tandem mirror with thermal barriers. Previously the author reported improved axial confinement with high end-plug potentials, consistent with thermal barrier operation. Now, the existence of thermal barriers in TMX-U confirmed by measuring the axial potential profile. Specifically, measured the change in energy of a 5-keV deuterium neutral beam that is injected nearly parallel to the axis and is ionized between the barrier and the central cell. The authors found that the barrier potential is lower than the central cell potential, as required for a thermal barrier. The peak potential is at least 2.4 keV, as determined from the minimum energy of end loss ions. In addition, radial transport is reduced by the use of floating and electrodes that map to concentric cylinders in the central cell. Sloshing ions continue to be microstable

  18. The Blood-Brain Barrier: An Engineering Perspective

    Directory of Open Access Journals (Sweden)

    Andrew eWong

    2013-08-01

    Full Text Available It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich’s first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and it remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore advances in our understanding of the structure and function of the blood-brain barrier are key to advances in treatment of a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.

  19. Performance of engineered barriers

    International Nuclear Information System (INIS)

    Rajaram, V.; Dean, P.V.; McLellan, S.A.

    1997-01-01

    Engineered barriers, both vertical and horizontal, have been used to isolate hazardous wastes from contact, precipitation, surface water and groundwater. The primary objective of this study was to determine the performance of subsurface barriers installed throughout the U.S. over the past 20 years to contain hazardous wastes. Evaluation of Resource Conservation and Recovery Act (RCRA) Subtitle C or equivalent caps was a secondary objective. A nationwide search was launched to select hazardous waste sites at which vertical barrier walls and/or caps had been used as the containment method. None of the sites selected had an engineered floor. From an initial list of 130 sites, 34 sites were selected on the basis of availability of monitoring data for detailed analysis of actual field performance. This paper will briefly discuss preliminary findings regarding the design, construction quality assurance/construction quality control (CQA/CQC), and monitoring at the 34 sites. In addition, the short-term performance of these sites (less than 5 years) is presented since very little long-term performance data was available

  20. Electron transmission through a periodically driven graphene magnetic barrier

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, R., E-mail: rbiswas.pkc@gmail.com [Department of Physics, P. K. College, Contai, Purba Medinipur, West Bengal – 721401 (India); Maiti, S. [Ajodhya Hills G.S.A.T High School, Ajodhya, Purulia, West Bengal – 723152 (India); Mukhopadhyay, S. [Purulia Zilla School, Dulmi Nadiha, Purulia, West Bengal – 723102 (India); Sinha, C. [Department of Physics, P. K. College, Contai, Purba Medinipur, West Bengal – 721401 (India); Department of Theoretical Physics, Indian Association for the Cultivation of Science, Jadavpur – 700032 (India)

    2017-05-10

    Electronic transport through graphene magnetic barriers is studied theoretically in presence of an external time harmonic scalar potential in the framework of non-perturbative Landau–Floquet Formalism. The oscillating field mostly suppresses the transmission for rectangular magnetic barrier structure and exhibits the Fano resonance for multiphoton processes due to the presence of bound state inside the barrier. While, for a pair of delta function barriers of larger separation, the oscillating potential suppresses the usual Fabry–Perot oscillations in the transmission and a new type of asymmetric Fano resonance is noted for smaller separation, occurring due to extended states between the barriers. - Highlights: • Tunnelling of the Dirac Fermions through oscillating pure magnetic barriers is reported for the first time. • The high energy transmission through a graphene magnetic barrier is suppressed by the application of time periodic modulation. • Suppression of the Fabry Perot transmission is noted due to the application of an external time harmonic potential. • Two kinds of the Fano resonances are noted in transmission through a pair of modulated δ-function magnetic barriers.