Effect of flow on endothelial endocytosis of nanocarriers targeted to ICAM-1

PubMed Central

Bhowmick, Tridib; Berk, Erik; Cui, Xiumin; Muzykantov, Vladimir R.; Muro, Silvia

2011-01-01

Delivery of drugs into the endothelium by nanocarriers targeted to endothelial determinants may improve treatment of vascular maladies. This is the case for intercellular adhesion molecule 1 (ICAM-1), a glycoprotein overexpressed on endothelial cells (ECs) in many pathologies. ICAM-1-targeted nanocarriers bind to and are internalized by ECs via a non-classical pathway, CAM-mediated endocytosis. In this work we studied the effects of endothelial adaptation to physiological flow on the endocytosis of model polymer nanocarriers targeted to ICAM-1 (anti-ICAM/NCs, ~180-nm diameter). Culturing established endothelial-like cells (EAhy926 cells) and primary human umbilical vein ECs (HUVECs) under 4 dyn/cm2 laminar shear stress for 24 h resulted in flow adaptation: cell elongation and formation of actin stress fibers aligned to the flow direction. Fluorescence microscopy showed that flow-adapted cells internalized anti-ICAM/NCs under flow, although at slower rate versus non flow-adapted cells under static incubation (~35% reduction). Uptake was inhibited by amiloride, whereas marginally affected by filipin and cadaverine, implicating that CAM-endocytosis accounts for anti-ICAM/NC uptake under flow. Internalization under flow was more modestly affected by inhibiting protein kinase C, which regulates actin remodeling during CAM-endocytosis. Actin recruitment to stress fibers that maintain the cell shape under flow may delay uptake of anti-ICAM/NCs under this condition by interfering with actin reorganization needed for CAM-endocytosis. Electron microscopy revealed somewhat slow, yet effective endocytosis of anti-ICAM/NCs by pulmonary endothelium after i.v. injection in mice, similar to that of flow-adapted cell cultures: ~40% (30 min) and 80% (3 h) internalization. Similar to cell culture data, uptake was slightly faster in capillaries with lower shear stress. Further, LPS treatment accelerated internalization of anti-ICAM/NCs in mice. Therefore, regulation of endocytosis of

ICAM-1 targeted catalase encapsulated PLGA-b-PEG nanoparticles against vascular oxidative stress.

PubMed

Sari, Ece; Tunc-Sarisozen, Yeliz; Mutlu, Hulya; Shahbazi, Reza; Ucar, Gulberk; Ulubayram, Kezban

2015-01-01

Targeted delivery of therapeutics is the favourable idea, whereas it is possible to distribute the therapeutically active drug molecule only to the site of action. For this purpose, in this study, catalase encapsulated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles were developed and an endothelial target molecule (anti-ICAM-1) was conjugated to this carrier system in order to decrease the oxidative stress level in the target site. According to the enzymatic activity results, initial catalase activity of nanoparticles was increased from 27.39 U/mg to up to 45.66 U/mg by adding 5 mg/mL bovine serum albumin (BSA). After 4 h, initial catalase activity was preserved up to 46.98% while free catalase retained less than 4% of its activity in proteolytic environment. Furthermore, FITC labelled anti-ICAM-1 targeted catalase encapsulated nanoparticles (anti-ICAM-1/CatNPs) were rapidly taken up by cultured endothelial cells and concomitantly endothelial cells were resistant to H2O2 induced oxidative impairment.

Radiation coloration resistant glass

DOEpatents

Tomozawa, Minoru; Watson, E. Bruce; Acocella, John

1986-01-01

A radiation coloration resistant glass is disclosed which is used in a radiation environment sufficient to cause coloration in most forms of glass. The coloration resistant glass includes higher proportions by weight of water and has been found to be extremely resistant to color change when exposed to such radiation levels. The coloration resistant glass is free of cerium oxide and has more than about 0.5% by weight water content. Even when exposed to gamma radiation of more than 10.sup.7 rad, the coloration resistant glass does not lose transparency.

Polymorphisms of IL-17 and ICAM-1 and their expression in Guillain-Barré syndrome.

PubMed

Kharwar, N K; Prasad, K N; Singh, K; Paliwal, V K; Modi, D R

2017-08-01

Guillain-Barré syndrome (GBS) is an acute inflammatory, autoimmune disorder of peripheral nervous system. Interleukin-17 (IL-17) and intercellular adhesion molecule-1 (ICAM-1) polymorphisms with higher expression levels have already been studied in many inflammatory and autoimmune diseases. However, the possible role of IL-17 and ICAM-1 polymorphisms in GBS remains unknown. Therefore, the current study investigated IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms. In this study, total 80 GBS patients and 75 normal healthy controls were included. IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms were performed using polymerase chain reaction -restriction fragment length polymorphism analysis. Further, the expression of ICAM-1 and IL-17 was determined by reverse-transcriptase PCR and enzyme-linked immunosorbent assay. IL-17 (Glu126Gly) mutant and ICAM-1 (Gly241Arg) heterozygous genotypes were strongly associated with increased risk of GBS (p < 0.016; OR = 3.706, 95% CI = 1.28-10.67; p < 0.001; OR = 4.148, 95% CI = 2.119-8.119, respectively). IL-17 and ICAM-1 genes showed significantly higher expression in GBS when compared with healthy controls. IL-17 and ICAM-1 polymorphisms showed significant association with GBS and their enhanced expressions have possible role in GBS development. IL-17 and ICAM-1 polymorphisms could be genetic markers to GBS susceptibility.

The ICAM-1 expression level determines the susceptibility of human endothelial cells to simulated microgravity.

PubMed

Buravkova, Ludmila B; Rudimov, Eugene G; Andreeva, Elena R; Grigoriev, Anatoly I

2018-03-01

Microgravity is a principal risk factor hampering human cardiovascular regulation during space flights. Endothelial dysfunction associated with the impaired integrity and uniformity of the monolayer represents a potential trigger for vascular damage. We characterized the expression profile of the multi-step cascade of adhesion molecules (ICAM-1, VCAM-1, E-selectin, VE-cadherin) in umbilical cord endothelial cells (ECs) after 24 h of exposure to simulated microgravity (SMG), pro-inflammatory cytokine TNF-α, and the combination of the two. Random Positioning Machine (RPM)-mediated SMG was used to mimic microgravity effects. SMG stimulated the expression of E-selectin, which is known to be involved in slowing leukocyte rolling. Primary ECs displayed heterogeneity with respect to the proportion of ICAM-1-positive cells. ECs were divided into two groups: pre-activated ECs displaying high proportion of ICAM-1 + -cells (ECs-1) (greater than 50%) and non-activated ECs with low proportion of ICAM-1 + -cells (ECs-2) (less than 25%). Only non-activated ECs-2 responded to SMG by elevating gene transcription and increasing ICAM-1 and VE-cadherin expression. This effect was enhanced after cumulative SMG-TNF-α exposure. ECs-1 displayed an unexpected decrease in number of E-selectin- and ICAM-1-positive ECs and pronounced up-regulation of VCAM1 upon activation of inflammation, which was partially abolished by SMG. Thus, non-activated ECs-2 are quite resistant to the impacts of microgravity and even exhibited an elevation of the VE-cadherin gene and protein expression, thus improving the integrity of the endothelial monolayer. Pre-activation of ECs with inflammatory stimuli may disturb the EC adhesion profile, attenuating its barrier function. These alterations may be among the mechanisms underlying cardiovascular dysregulation in real microgravity conditions. © 2017 Wiley Periodicals, Inc.

Distinct subcellular trafficking resulting from monomeric vs multimeric targeting to endothelial ICAM-1: implications for drug delivery.

PubMed

Ghaffarian, Rasa; Muro, Silvia

2014-12-01

Ligand-targeted, receptor-mediated endocytosis is commonly exploited for intracellular drug delivery. However, cells-surface receptors may follow distinct endocytic fates when bound by monomeric vs multimeric ligands. Our purpose was to study this paradigm using ICAM-1, an endothelial receptor involved in inflammation, to better understand its regulation and potential for drug delivery. Our procedure involved fluorescence microscopy of human endothelial cells to determine the endocytic behavior of unbound ICAM-1 vs ICAM-1 bound by model ligands: monomeric (anti-ICAM) vs multimeric (anti-ICAM biotin-streptavidin conjugates or anti-ICAM coated onto 100 nm nanocarriers). Our findings suggest that both monomeric and multimeric ligands undergo a similar endocytic pathway sensitive to amiloride (∼50% inhibition), but not inhibitors of clathrin-pits or caveoli. After 30 min, ∼60-70% of both ligands colocalized with Rab11a-compartments. By 3-5 h, ∼65-80% of multimeric anti-ICAM colocalized with perinuclear lysosomes with ∼60-80% degradation, while 70% of monomeric anti-ICAM remained associated with Rab11a at the cell periphery and recycled to and from the cell-surface with minimal (<10%) lysosomal colocalization and minimal (≤15%) degradation. In the absence of ligands, ICAM-1 also underwent amiloride-sensitive endocytosis with peripheral distribution, suggesting that monomeric (not multimeric) anti-ICAM follows the route of this receptor. In conclusion, ICAM-1 can mediate different intracellular itineraries, revealing new insight into this biological pathway and alternative avenues for drug delivery.

PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3β/GATA-6 signaling pathways in TNF-α-activated human endothelial cells.

PubMed

Tsoyi, Konstantin; Jang, Hwa Jin; Nizamutdinova, Irina Tsoy; Park, Kyungok; Kim, Young Min; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Chang, Ki Churl

2010-11-01

Phosphotase and tensin homolog deleted on chromosome 10 (PTEN) is a potent negative regulator of PI3K/Akt pathway. Here, we tried to elucidate the role of PTEN in the regulation of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1, induced by TNF-α in human endothelial cells (ECs). Transfection with PTEN overexpressing vector resulted in the significant decrease in phosphorylation of Akt in TNF-α-treated ECs. PTEN strongly inhibited VCAM-1 but not ICAM-1, however this inhibitory effect was reversed by co-transfection with constitutively active-Akt (CA-Akt-HA) in TNF-α-stimulated ECs. Additionally, silencing of PTEN with specific siRNA showed significant increase of phosphor-Akt compared with TNF-α alone treated ECs. siPTEN significantly upregulated VCAM-1 but was indifferent to ICAM-1 in TNF-α-treated cells. Further, chromatin immunoprecipitation (ChIP) assay showed that PTEN targets GATA-6 but not IRF-1 binding to VCAM-1 promoter. In addition, GATA-6 is associated with glycogen synthesis kinase-3beta (GSK-3β) which is in turn regulated by PTEN-dependent Akt activity. Finally, PTEN significantly prevented monocyte adhesion to TNF-α-induced ECs probably through VCAM-1 regulation. It is concluded that PTEN selectively inhibits expression of VCAM-1 but not ICAM-1 through modulation of PI3K/Akt/GSK-3β/GATA-6 signaling cascade in TNF-α-treated ECs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Concluding remarks to ICAME2011

NASA Astrophysics Data System (ADS)

Campbell, S. J.

2012-03-01

An overview of the main aspects of ICAME2011 - tutorial lectures, oral and poster presentations, evening sessions - is presented along with a brief outline of several of the scientific highlights. Among other topics considered are the involvements of young scientists and female scientists, and operation of the oral and poster sessions. Despite the most challenging combinations of circumstances in the lead up to ICAME2011 that resulted in the change of venue at an advanced stage from Tokyo to Kobe, the Committee organised a high quality conference with many positive outcomes for the future. The Mössbauer community acknowledges and appreciates these efforts greatly.

Serological level of ICAM and ELAM adhesion molecules in allergic vascularitis.

PubMed

Alecu, M; Coman, G; Gălăţescu, E

1997-01-01

A 24-patient lot with hypersensitivity vasculitis was investigated for serological determinations of ICAM and ELAM adhesion molecules. Determinations were made in attack and in remission. Over two thirds of the cases presented elevated serological levels of ICAM and ELAM in attack, with twofold higher values than normal. In remission, in the absence of clinical signs, ICAM and ELAM values were normal in 19 cases (ICAM) and 22 cases (ELAM). Serological level of ICAM and ELAM was concordant with serological level of IL-2, IL-6, circulating immune complexes and clinical status. The increased values of ICAM and ELAM are due to the expression of these molecules both on the surface of endothelial cells and on immune cells. The adherence of leukocytes on the endothelial cells, by adhesion molecules involvement, followed by their extravasation represents an important event in the vascular lesion pathogeny of the hypersensitivity vasculitis.

The ICAM-1 antisense oligonucleotide ISIS-3082 prevents the development of postoperative ileus in mice

PubMed Central

The, Frans O; de Jonge, Wouter J; Bennink, Roel J; van den Wijngaard, Rene M; Boeckxstaens, Guy E

2005-01-01

Intestinal manipulation (IM) during abdominal surgery triggers the influx of inflammatory cells, leading to postoperative ileus. Prevention of this local muscle inflammation, using intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1-specific antibodies, has been shown to shorten postoperative ileus. However, the therapeutic use of antibodies has considerable disadvantages. The aim of the current study was to evaluate the effect of ISIS-3082, a mouse-specific ICAM-1 antisense oligonucleotide, on postoperative ileus in mice. Mice underwent a laparotomy or a laparotomy combined with IM after treatment with ICAM-1 antibodies, 0.1–10 mg kg−1 ISIS-3082, saline or ISIS-8997 (scrambled control antisense oligonucleotides, 1 and 3 mg kg−1). At 24 h after surgery, gastric emptying of a 99mTC labelled semi-liquid meal was determined using scintigraphy. Intestinal inflammation was assessed by myeloperoxidase (MPO) activity in ileal muscle whole mounts. IM significantly reduced gastric emptying compared to laparotomy. Pretreatment with ISIS-3082 (0.1–1 mg kg−1) as well as ICAM-1 antibodies (10 mg kg−1), but not ISIS-8997 or saline, improved gastric emptying in a dose-dependent manner. This effect diminished with higher doses of ISIS-3082 (3–10 mg kg−1). Similarly, ISIS-3082 (0.1–1 mg kg−1) and ICAM-1 antibodies, but not ISIS-8997 or higher doses of ISIS-3082 (3–10 mg kg−1), reduced manipulation-induced inflammation. Immunohistochemistry showed reduction of ICAM-1 expression with ISIS-3082 only. ISIS-3082 pretreatment prevents postoperative ileus in mice by reduction of manipulation-induced local intestinal muscle inflammation. Our data suggest that targeting ICAM-1 using antisense oligonucleotides may represent a new therapeutic approach to the prevention of postoperative ileus. PMID:15997238

The ICAM-1 antisense oligonucleotide ISIS-3082 prevents the development of postoperative ileus in mice.

PubMed

The, Frans O; de Jonge, Wouter J; Bennink, Roel J; van den Wijngaard, Rene M; Boeckxstaens, Guy E

2005-09-01

Intestinal manipulation (IM) during abdominal surgery triggers the influx of inflammatory cells, leading to postoperative ileus. Prevention of this local muscle inflammation, using intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1-specific antibodies, has been shown to shorten postoperative ileus. However, the therapeutic use of antibodies has considerable disadvantages. The aim of the current study was to evaluate the effect of ISIS-3082, a mouse-specific ICAM-1 antisense oligonucleotide, on postoperative ileus in mice. Mice underwent a laparotomy or a laparotomy combined with IM after treatment with ICAM-1 antibodies, 0.1-10 mg kg(-1) ISIS-3082, saline or ISIS-8997 (scrambled control antisense oligonucleotides, 1 and 3 mg kg(-1)). At 24 h after surgery, gastric emptying of a 99mTC labelled semi-liquid meal was determined using scintigraphy. Intestinal inflammation was assessed by myeloperoxidase (MPO) activity in ileal muscle whole mounts. IM significantly reduced gastric emptying compared to laparotomy. Pretreatment with ISIS-3082 (0.1-1 mg kg(-1)) as well as ICAM-1 antibodies (10 mg kg(-1)), but not ISIS-8997 or saline, improved gastric emptying in a dose-dependent manner. This effect diminished with higher doses of ISIS-3082 (3-10 mg kg(-1)). Similarly, ISIS-3082 (0.1-1 mg kg(-1)) and ICAM-1 antibodies, but not ISIS-8997 or higher doses of ISIS-3082 (3-10 mg kg(-1)), reduced manipulation-induced inflammation. Immunohistochemistry showed reduction of ICAM-1 expression with ISIS-3082 only. ISIS-3082 pretreatment prevents postoperative ileus in mice by reduction of manipulation-induced local intestinal muscle inflammation. Our data suggest that targeting ICAM-1 using antisense oligonucleotides may represent a new therapeutic approach to the prevention of postoperative ileus.

VCAM1 and ICAM1 expression in oral lichen planus

PubMed Central

Seyedmajidi, Maryam; Shafaee, Shahryar; Bijani, Ali; Bagheri, Soodabeh

2013-01-01

Oral lichen planus is a chronic inflammatory immune-mediated disease. ICAM-1 and VCAM-1 are vascular adhesion molecules that their receptors are located on endothelial cells and leukocytes. The aim of this study is the immunohistochemical evaluation of VCAM1 and ICAM1 in oral lichen planus and to compare these two markers with normal mucosa for evaluation of angiogenesis. This descriptive-analytical study was performed on 70 paraffined blocks of oral lichen planus and 30 normal mucosa samples taken from around the lesions. Samples were stained with H & E and then with Immunohistochemistry using monoclonal mouse anti human VCAM1 (CD106), & monoclonal mouse anti human ICAM1(CD54) for confirmation of diagnosis. Slides were evaluated under light microscope and VCAM1 and ICAM1 positive cells (endothelial cells and leukocytes) were counted. Data were analyzed with Mann-Whitney test, Wilcoxon and Chi-Square and p<0.001 was declared significant. VCAM1 and ICAM1 expression significantly increased compared to normal mucosa in oral lichen planus according to the percentage of stained cells (p=0.000& p=0.000, Mann-Whitney test). Thirty cases of oral normal mucosa associated with lichen planus showed that the VCAM1 has increased significantly in comparison to normal mucosa (p<0.001). Also, ICAM1 expression between lichen planus and normal mucosa, showed a significantly difference (p<0.001). A significant difference between VCAM1 and ICAM1 expression and type of lichen planus was not observed (p>0.05). Regarding the results, it seems that high expression of VCAM1 and ICAM1 is related to oral lichen planus. PMID:24551788

ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia.

PubMed

Woodfin, Abigail; Beyrau, Martina; Voisin, Mathieu-Benoit; Ma, Bin; Whiteford, James R; Hordijk, Peter L; Hogg, Nancy; Nourshargh, Sussan

2016-02-18

Intracellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed on the cell surface of numerous cell types such as endothelial and epithelial cells, vascular smooth muscle cells, and certain leukocyte subsets. With respect to the latter, ICAM-1 has been detected on neutrophils in several clinical and experimental settings, but little is known about the regulation of expression or function of neutrophil ICAM-1. In this study, we report on the de novo induction of ICAM-1 on the cell surface of murine neutrophils by lipopolysaccharide (LPS), tumor necrosis factor, and zymosan particles in vitro. The induction of neutrophil ICAM-1 was associated with enhanced phagocytosis of zymosan particles and reactive oxygen species (ROS) generation. Conversely, neutrophils from ICAM-1-deficient mice were defective in these effector functions. Mechanistically, ICAM-1-mediated intracellular signaling appeared to support neutrophil ROS generation and phagocytosis. In vivo, LPS-induced inflammation in the mouse cremaster muscle and peritoneal cavity led to ICAM-1 expression on intravascular and locally transmigrated neutrophils. The use of chimeric mice deficient in ICAM-1 on myeloid cells demonstrated that neutrophil ICAM-1 was not required for local neutrophil transmigration, but supported optimal intravascular and extravascular phagocytosis of zymosan particles. Collectively, the present results shed light on regulation of expression and function of ICAM-1 on neutrophils and identify it as an additional regulator of neutrophil effector responses in host defense. © 2016 by The American Society of Hematology.

Induction of ICAM-1 Expression in Mouse Embryonic Fibroblasts Cultured on Fibroin-Gelatin Scaffolds

PubMed Central

Nosenko, M. A.; Maluchenko, N. V.; Drutskaya, M. S.; Arkhipova, A. Y.; Agapov, I. I.; Nedospasov, S. A.; Moisenovich, M. M.

2017-01-01

Culturing of allogeneic or autologous cells in three-dimensional bioresorbable scaffolds is an important step in the engineering of constructs for regenerative medicine, as well as for experimental systems to study the mechanisms of cell differentiation and cell-to-cell interaction. Artificial substrates can modulate the phenotype and functional activity of immobilized cells. Investigating these changes is important for understanding the fundamental processes underlying cellular interactions in a 3D microenvironment and for improving tissue-engineered structures. In this study, we investigated the expression of the ICAM-1 adhesion molecule in mouse embryonic fibroblasts (MEF) when cultured on gelatin-fibroin scaffolds. Increased expression of ICAM-1 in MEF was detected only under 3D culture conditions both at the mRNA and protein levels. At the same time, the MEF cultured on various substrates did not oerexpress MAdCAM-1, indicating the selective effect of 3D culture conditions on ICAM-1 expression. One possible mechanism for ICAM-1 induction in MEF is associated with the activation of AP-1, since expression of c-Fos and Junb (but not cJun and Jund) was increased in MEF in 3D. When cultured under 2D conditions, the expression level of AP-1 components did not change. PMID:29104780

Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression

PubMed Central

Huang, Chongbiao; Li, Na; Li, Zengxun; Chang, Antao; Chen, Yanan; Zhao, Tiansuo; Li, Yang; Wang, Xiuchao; Zhang, Wei; Wang, Zhimin; Luo, Lin; Shi, Jingjing; Yang, Shengyu; Ren, He; Hao, Jihui

2017-01-01

Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation. Mechanistically, IL-35 promotes ICAM1 overexpression through a GP130-STAT1 signalling pathway, which facilitates endothelial adhesion and transendothelial migration via an ICAM1–fibrinogen–ICAM1 bridge. In an orthotopic xenograft model, IL-35 promotes spontaneous pancreatic cancer metastasis in an ICAM1-dependent manner. Together, our results indicate additional functions of IL-35 in promoting PDAC metastasis through mediating ICAM1 expression. PMID:28102193

Enhancement of CCL15 expression and monocyte adhesion to endothelial cells (ECs) after hypoxia/reoxygenation and induction of ICAM-1 expression by CCL15 via the JAK2/STAT3 pathway in ECs.

PubMed

Park, Keun Hyung; Lee, Tae Hoon; Kim, Chan Woo; Kim, Jiyoung

2013-06-15

CCL15, a member of the CC chemokine family, is a potent chemoattractant for leukocytes and endothelial cells (ECs). Given that chemokines play key roles in vascular inflammation, we investigated the effects of hypoxia/reoxygenation (H/R) on expression of human CCL15 and a role of CCL15 in upregulating ICAM-1 in ECs. We found that exposure of ECs to H/R increased expression of CCL15 and ICAM-1, which resulted in an increase in monocyte adhesivity to the ECs. Further studies revealed that knockdown of CCL15 or CCR1 attenuated expression of ICAM-1 in ECs after H/R, suggesting that expression of ICAM-1 is upregulated by CCL15. Stimulation of ECs with CCL15 significantly increased expression of ICAM-1 predominantly via the CCR1 receptor. We observed that phosphorylation of JAK2 and STAT3 was stimulated by CCL15 treatment of ECs. Results from reporter and chromatin immunoprecipitation assays revealed that CCL15 activates transcription from the IFN-γ activation site promoter and stimulates binding of STAT3 to the ICAM-1 promoter. Our data also showed that CCL15 increased cell adhesion of human monocytes to ECs under static and shear-stress conditions. Pretreatment of these cells with inhibitors for JAK, PI3K, and AKT prevented the CCL15-induced expression of ICAM-1 and monocyte adhesion to ECs, suggesting the involvement of those signaling molecules in ICAM-1 gene activation by CCL15. The results suggest that CCR1 and its ligands may be a potential target for treating inflammatory diseases involving upregulation of cell adhesion molecules.

Hug tightly and say goodbye: role of endothelial ICAM-1 in leukocyte transmigration.

PubMed

Rahman, Arshad; Fazal, Fabeha

2009-04-01

Stable adhesion of leukocytes to endothelium is crucial for transendothelial migration (TEM) of leukocytes evoked during inflammatory responses, immune surveillance, and homing and mobilization of hematopoietic progenitor cells. The basis of stable adhesion involves expression of intercellular adhesion molecule-1 (ICAM-1), an inducible endothelial adhesive protein that serves as a counter-receptor for beta(2)-integrins on leukocytes. Interaction of ICAM-1 with beta(2)-integrins enables leukocytes to adhere firmly to the vascular endothelium and subsequently, to migrate across the endothelial barrier. The emerging paradigm is that ICAM-1, in addition to firmly capturing leukocytes, triggers intracellular signaling events that may contribute to active participation of the endothelium in facilitating the TEM of adherent leukocytes. The nature, duration, and intensity of ICAM-1-dependent signaling events may contribute to the determination of the route (paracellular vs. transcellular) of leukocyte passage; these aspects of ICAM-1 signaling may in turn be influenced by density and distribution of ICAM-1 on the endothelial cell surface, the source of endothelial cells it is present on, and the type of leukocytes with which it is engaged. This review summarizes our current understanding of the "ICAM-1 paradigm" of TEM with an emphasis on the signaling events mediating ICAM-1 expression and activated by ICAM-1 engagement in endothelial cells.

ICAM-1 Targeting of Doxorubicin-Loaded PLGA Nanoparticles to Lung Epithelial Cells

PubMed Central

Chuda, Chittasupho; Sheng-Xue, Xie; Abdulgader, Baoum; Tatyana, Yakovleva; Teruna, Siahaan J.; Cory, Berkland

2009-01-01

Interaction of leukocyte function associated antigen-1 (LFA-1) on T-lymphoctytes and intercellular adhesion molecule-1 (ICAM-1) on epithelial cells controls leukocyte adhesion, spreading, and extravasation. This process plays an important role in leukocyte recruitment to a specific site of inflammation and has been indentified as a biomarker for certain types of carcinomas. Cyclo-(1,12)-PenITDGEATDSGC (cLABL) has been shown to inhibit LFA-1 and ICAM-1 interaction via binding to ICAM-1. In addition, cLABL has been shown to internalize after binding ICAM-1. The possibility of using cLABL conjugated nanoparticles (cLABL-NP) as a targeted and controlled release drug delivery system has been investigated in this study. The cLABL peptide was conjugated to a modified Pluronic® surfactant on poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles. The cLABL-NP showed more rapid cellular uptake by A549 lung epithelial cells compared to nanoparticles without peptide. The specificity of ICAM-1 mediated internalization was confirmed by blocking the uptake of cLABL-NP to ICAM-1 using free cLABL peptide to block the binding of cLABL-NP to ICAM-1 on the cell surface. Cell studies suggested that cLABL-NPs targeted encapsulated doxorubicin to ICAM-1 expressing cells. Cytotoxicity assay confirmed the activity of the drug incorporated in nanoparticles. Sustained release of doxorubicin afforded by PLGA nanoparticles may enable cLABL-NP as a targeted, controlled release drug delivery system. PMID:19429421

Radiation resistence of microorganisms from radiation sterilization processing environments

NASA Astrophysics Data System (ADS)

Sabovljev, Svetlana A.; Žunić, Zora S.

The radiation resistance of microorganisms was examined on the samples of dust collected from the radiation sterilization processing environments including assembly, storage, and sterilization plant areas. The isolation of radiation resistant strains was performed by irradiation with screening doses ranging from 10 to 35 kGy and test pieces containing 10 6 to 10 8 CFU in dried serum-broth, representing 100 to 5000 colonies of primary cultures of microorganisms from 7 different sites. In an examination of 16900 colonies of aerobic microorganisms from 3 hygienically controlled production sites and 4 uncontrolled ones, 30 strains of bacteria were isolated. Of those 15 were classified as genus Bacillus, 9 as Micrococcus and 6 as Sarcina. All of the 15 strains of Gram positive sporeforming aerobic rods exhibited an exponential decrease in the surviving fraction as a function of dose, indicating that the inactivation of spores of aerobic rods is a consequence of a single energy deposition into the target. All strains were found to be moderately resistant to radiation with D-6 values (dose required to reduce survival to 6 log cycles) between 18 and 26 kGy. All of the isolated Gram positive cocci showed inactivation curves having a shoulder, indicating that different processes are involved in the inactivation of these cells, e.g. accumulation of sublethal lesions, or final repair capacity of potential lethal lesions. Moderate radiation resistance was observed in 13 strains with D-6 values between 16 to 30 kGy. Two slow-growing, red pigmented strains tentatively classified as genus Micrococcus isolated from uncontrolled sites (human dwellings) were exceptionally resistant with D-6 more than 45 kGy. For hygienically controlled sites, Gram positive spereforming rods composed two thirds of the resistant microflora, while Gram positive cocci comprised one third. For hygienically uncontrolled sites this ratio was reversed. An assumption is made that one isolated strain has grown

Integrated Computer-Aided Manufacturing (ICAM) Architecture. Part 3. Volume 7. MFG01 Glossary.

DTIC Science & Technology

1983-09-01

lat oe C % 000 Sj C4 le ’ 4, 4,4 2:4 tj t*K l- X: 44 0’~ k IW- C4 % 40 Go r 00 c ~ IL P v C c -. . v IL zl - 4 1 S . v I .I a w I 1 v c u > c- -FT U 4...CC c .C C aI o , 0 A Z . 6--c 0 cCrV 46 a .0 b. 1 c 1 . Ga, v 0 M 0 44 c c c f-V - 4 0 aLS C C - . l-l - 2 - 0 S- C (~ b , J O’~ 0 .4. hSV b... ~ b...RD-R144 426 INTEGRATED COMPUTER-AIDED MANUFACTURING (ICAM)_ 1 /3 ARCHITECTURE PART 3 VOLUME.. (U) SOFTECH INC WALTHAM MRR HEINE ET RL. SEP 83 RFWRL-TR

PI3Kδ promotes CD4(+) T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1.

PubMed

Garçon, Fabien; Okkenhaug, Klaus

2016-05-01

Activation of T lymphocytes by peptide/major histocompatibility complex on antigen-presenting cells (APCs) involves dynamic contacts between the two cells, during which T cells undergo marked morphological changes. These interactions are facilitated by integrins. Activation of the T cells increases the binding of the integrin lymphocyte function-associated antigen 1 (LFA-1) expressed by T cells to intercellular adhesion molecule (ICAM)-1 and ICAM-2 expressed by APCs. The signalling pathways that control integrin affinities are incompletely defined. The phosphoinositide 3-kinases (PI3Ks) generate second-messenger signalling molecules that control cell growth, proliferation, differentiation and trafficking. Here we show that in T cells, PI3Kδ attenuates the activation of Rac1, but sustains the activation of Rap1. Consequently, PI3Kδ increases LFA-1-dependent adhesion to form stable conjugates with APCs. Increased Rap1 activity and LFA-1 adhesion were only in part mediated by the downstream kinase Akt, suggesting the involvement of additional phosphatidylinositol(3,4,5)P3-binding proteins. These results establish a link between PI3K activity, cytoskeletal changes and integrin binding and help explain the impaired T-cell-dependent immune responses in PI3Kδ-deficient mice.

Regulation of ICAM-1 in cells of the monocyte/macrophage system in microgravity.

PubMed

Paulsen, Katrin; Tauber, Svantje; Dumrese, Claudia; Bradacs, Gesine; Simmet, Dana M; Gölz, Nadine; Hauschild, Swantje; Raig, Christiane; Engeli, Stephanie; Gutewort, Annett; Hürlimann, Eva; Biskup, Josefine; Unverdorben, Felix; Rieder, Gabriela; Hofmänner, Daniel; Mutschler, Lisa; Krammer, Sonja; Buttron, Isabell; Philpot, Claudia; Huge, Andreas; Lier, Hartwin; Barz, Ines; Engelmann, Frank; Layer, Liliana E; Thiel, Cora S; Ullrich, Oliver

2015-01-01

Cells of the immune system are highly sensitive to altered gravity, and the monocyte as well as the macrophage function is proven to be impaired under microgravity conditions. In our study, we investigated the surface expression of ICAM-1 protein and expression of ICAM-1 mRNA in cells of the monocyte/macrophage system in microgravity during clinostat, parabolic flight, sounding rocket, and orbital experiments. In murine BV-2 microglial cells, we detected a downregulation of ICAM-1 expression in clinorotation experiments and a rapid and reversible downregulation in the microgravity phase of parabolic flight experiments. In contrast, ICAM-1 expression increased in macrophage-like differentiated human U937 cells during the microgravity phase of parabolic flights and in long-term microgravity provided by a 2D clinostat or during the orbital SIMBOX/Shenzhou-8 mission. In nondifferentiated U937 cells, no effect of microgravity on ICAM-1 expression could be observed during parabolic flight experiments. We conclude that disturbed immune function in microgravity could be a consequence of ICAM-1 modulation in the monocyte/macrophage system, which in turn could have a strong impact on the interaction with T lymphocytes and cell migration. Thus, ICAM-1 can be considered as a rapid-reacting and sustained gravity-regulated molecule in mammalian cells.

Regulation of ICAM-1 in Cells of the Monocyte/Macrophage System in Microgravity

PubMed Central

Paulsen, Katrin; Tauber, Svantje; Dumrese, Claudia; Bradacs, Gesine; Simmet, Dana M.; Gölz, Nadine; Hauschild, Swantje; Raig, Christiane; Engeli, Stephanie; Gutewort, Annett; Hürlimann, Eva; Biskup, Josefine; Rieder, Gabriela; Hofmänner, Daniel; Mutschler, Lisa; Krammer, Sonja; Philpot, Claudia; Huge, Andreas; Lier, Hartwin; Barz, Ines; Engelmann, Frank; Layer, Liliana E.; Thiel, Cora S.

2015-01-01

Cells of the immune system are highly sensitive to altered gravity, and the monocyte as well as the macrophage function is proven to be impaired under microgravity conditions. In our study, we investigated the surface expression of ICAM-1 protein and expression of ICAM-1 mRNA in cells of the monocyte/macrophage system in microgravity during clinostat, parabolic flight, sounding rocket, and orbital experiments. In murine BV-2 microglial cells, we detected a downregulation of ICAM-1 expression in clinorotation experiments and a rapid and reversible downregulation in the microgravity phase of parabolic flight experiments. In contrast, ICAM-1 expression increased in macrophage-like differentiated human U937 cells during the microgravity phase of parabolic flights and in long-term microgravity provided by a 2D clinostat or during the orbital SIMBOX/Shenzhou-8 mission. In nondifferentiated U937 cells, no effect of microgravity on ICAM-1 expression could be observed during parabolic flight experiments. We conclude that disturbed immune function in microgravity could be a consequence of ICAM-1 modulation in the monocyte/macrophage system, which in turn could have a strong impact on the interaction with T lymphocytes and cell migration. Thus, ICAM-1 can be considered as a rapid-reacting and sustained gravity-regulated molecule in mammalian cells. PMID:25654110

Blocking pulmonary ICAM-1 expression ameliorates lung injury in established diet-induced pancreatitis.

PubMed

Lundberg, A H; Fukatsu, K; Gaber, L; Callicutt, S; Kotb, M; Wilcox, H; Kudsk, K; Gaber, A O

2001-02-01

To determine whether blocking the cell surface expression of intracellular adhesion molecules (ICAM-1) in established severe acute pancreatitis (AP) would ameliorate pulmonary injury. Lung injury in AP is in part mediated by infiltrating leukocytes, which are directed to lung tissue by ICAM-l. The authors' laboratory has previously demonstrated that AP results in overproduction of inflammatory cytokines, upregulation of pulmonary ICAM-1 expression, and a concomitant infiltration of neutrophils, which results in lung injury. Young female mice were fed a choline-deficient/ethionine-supplemented diet to induce AP and were treated with a blocking dose of monoclonal antibody specific to the ICAM-1 receptor. Antibody treatment was administered at 72, 96, and 120 hours after beginning the diet, and all animals were killed at 144 hours. The degree of pancreatitis was evaluated by serum biochemical and tumor necrosis factor alpha levels as well as histology. The dual radiolabeled monoclonal antibody method was used to quantitate ICAM-1 cell surface expression in pulmonary tissue. Lung injury was assessed histologically and by determining lung microvascular permeability by measuring accumulated 125I-radiolabeled albumin. Pulmonary neutrophil sequestration was determined by the myeloperoxidase assay. All mice developed severe AP, and pancreatic injury was equally severe in both treated and untreated groups. Pulmonary ICAM-1 expression was significantly upregulated in animals with AP compared with controls. Treatment with a blocking dose of anti-ICAM-1 antibody after the induction of AP resulted in inhibited ICAM-1 cell surface expression to near control levels. Compared to untreated animals with AP, mice treated with anti-ICAM-1 mice had significantly reduced histologic lung injury and neutrophil sequestration, and a decreased microvascular permeability by more than twofold. These results demonstrate for the first time that treatment targeting the cell surface expression of

High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria.

PubMed

Adukpo, Selorme; Kusi, Kwadwo A; Ofori, Michael F; Tetteh, John K A; Amoako-Sakyi, Daniel; Goka, Bamenla Q; Adjei, George O; Edoh, Dominic A; Akanmori, Bartholomew D; Gyan, Ben A; Dodoo, Daniel

2013-01-01

Cerebral malaria (CM) is responsible for most of the malaria-related deaths in children in sub-Saharan Africa. Although, not well understood, the pathogenesis of CM involves parasite and host factors which contribute to parasite sequestration through cytoadherence to the vascular endothelium. Cytoadherence to brain microvasculature is believed to involve host endothelial receptor, CD54 or intercellular adhesion molecule (ICAM)-1, while other receptors such as CD36 are generally involved in cytoadherence of parasites in other organs. We therefore investigated the contributions of host ICAM-1 expression and levels of antibodies against ICAM-1 binding variant surface antigen (VSA) on parasites to the development of CM. Paediatric malaria patients, 0.5 to 13 years were recruited and grouped into CM and uncomplicated malaria (UM) patients, based on well defined criteria. Standardized ELISA protocol was used to measure soluble ICAM-1 (sICAM-1) levels from acute plasma samples. Levels of IgG to CD36- or ICAM-1-binding VSA were measured by flow cytometry during acute and convalescent states. Wilcoxon sign rank-test analysis to compare groups revealed association between sICAM-1 levels and CM (p<0.0037). Median levels of antibodies to CD36-binding VSA were comparable in the two groups at the time of admission and 7 days after treatment was initiated (p>0.05). Median levels of antibodies to CD36-binding VSAs were also comparable between acute and convalescent samples within any patient group. Median levels of antibodies to ICAM-1-binding VSAs were however significantly lower at admission time than during recovery in both groups. High levels of sICAM-1 were associated with CM, and the sICAM-1 levels may reflect expression levels of the membrane bound form. Anti-VSA antibody levels to ICAM-binding parasites was more strongly associated with both UM and CM than antibodies to CD36 binding parasites. Thus, increasing host sICAM-1 levels were associated with CM whilst antibodies

Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.

PubMed

Muro, Silvia; Schuchman, Edward H; Muzykantov, Vladimir R

2006-01-01

Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.

Silibinin Inhibits ICAM-1 Expression via Regulation of N-Linked and O-Linked Glycosylation in ARPE-19 Cells

PubMed Central

Chen, Yi-Hao; Chen, Ching-Long; Liang, Chang-Min; Liang, Jy-Been; Tai, Ming-Cheng; Chang, Yun-Hsiang; Lu, Da-Wen; Chen, Jiann-Torng

2014-01-01

To evaluate the effects of silibinin on intercellular adhesion molecule-1 (ICAM-1) expression, we used ARPE-19 cells as a model in which tumor necrosis factor (TNF-α) and interferon (IFN-γ) enhanced ICAM-1 expression. This upregulation was inhibited by silibinin. In an adherence assay using ARPE-19 and THP-1 cells, silibinin inhibited the cell adhesion function of ICAM-1. The inhibitory effects of silibinin on ICAM-1 expression were mediated via the blockage of nuclear translocation of p65 proteins in TNF-α and phosphorylation of STAT1 in IFN-γ-stimulated cells. In addition, silibinin altered the degree of N-linked glycosylation posttranslationally in ARPE-19 cells by significantly enhancing MGAT3 gene expression. Silibinin can increase the O-GlcNAc levels of glycoproteins in ARPE-19 cells. In a reporter gene assay, PUGNAc, which can also increase O-GlcNAc levels, inhibited NF-κB reporter activity in TNF-α-induced ARPE-19 cells and this process was augmented by silibinin treatment. Overexpression of OGT gene was associated with reduced TNF-α-induced ICAM-1 levels, which is consistent with that induced by silibinin treatment. Taken together, silibinin inhibits ICAM-1 expression and its function through altered O-linked glycosylation in NF-κB and STAT1 signaling pathways and decreases the N-linked glycosylation of ICAM-1 transmembrane protein in proinflammatory cytokine-stimulated ARPE-19 cells. PMID:25032222

Diversity of ionizing radiation-resistant bacteria obtained from the Taklimakan Desert.

PubMed

Yu, Li Zhi-Han; Luo, Xue-Song; Liu, Ming; Huang, Qiaoyun

2015-01-01

So far, little is known about the diversity of the radiation-resistant microbes of the hyperarid Taklimakan Desert. In this study, ionizing radiation (IR)-resistant bacteria from two sites in Xinjiang were investigated. After exposing the arid (water content of 0.8 ± 0.3%) and non-arid (water content of 21.3 ± 0.9%) sediment samples to IR of 3000 Gy using a (60)Co source, a total of 52 γ-radiation-resistant bacteria were isolated from the desert sample. The 16S rRNA genes of all isolates were sequenced. The phylogenetic tree places these isolates into five groups: Cytophaga-Flavobacterium-Bacteroides, Proteobacteria, Deinococcus-Thermus, Firmicutes, and Actinobacteria. Interestingly, this is the first report of radiation-resistant bacteria belonging to the genera Knoellia, Lysobacter, Nocardioides, Paracoccus, Pontibacter, Rufibacter and Microvirga. The 16s rRNA genes of four isolates showed low sequence similarities to those of the published species. Phenotypic analysis showed that all bacteria in this study are able to produce catalase, suggesting that these bacteria possess reactive oxygen species (ROS)-scavenging enzymes. These radiation-resistant bacteria also displayed diverse metabolic properties. Moreover, their radiation resistances were found to differ. The diversity of the radiation-resistant bacteria in the desert provides further ecological support for the hypothesis that the ionizing-radiation resistance phenotype is a consequence of the evolution of ROS-scavenging systems that protect cells against oxidative damage caused by desiccation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma concentration of soluble intercellular adhesion molecule-1 (sICAM-1) is elevated in type 2 diabetic patients, and sICAM-1 synthesis is associated with leptin-induced activation of the mitogen-activated protein kinase (MAPK) pathway.

PubMed

Cha, Jin Joo; Hyun, Young Youl; Jee, Yi Hwa; Lee, Mi Jin; Han, Kum Hyun; Kang, Young Sun; Han, Sang Youb; Cha, Dae Ryong

2013-08-01

The intercellular adhesion molecule-1 (ICAM-1) and leptin are important inflammatory biomarkers. We investigated whether plasma-soluble ICAM-1 levels were related to the diabetic nephropathy and systemic inflammation. One hundred forty-seven type 2 diabetic patients and 46 healthy control subjects were studied. Plasma sICAM-1 concentrations were significantly higher in the diabetic groups than controls and increased significantly as diabetic nephropathy advanced. Plasma sICAM-1 levels were positively correlated with body mass index, fasting and postprandial blood glucose, urinary albumin excretion, and negatively correlated with creatinine clearance. Multiple regression analysis showed that plasma leptin levels were associated with a significant increase in plasma sICAM-1 levels. In cultured HUVECs, leptin increased ICAM-1 production in a dose-dependent manner, and this stimulating effect of leptin on ICAM-1 expression was reversed by MEK inhibitor, PD98059. Overall, these findings suggest that activation of leptin synthesis in a diabetic environment promotes ICAM-1 activation via mitogen-activated protein kinase pathway in type 2 diabetic patients.

MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression in inflammatory myopathies.

PubMed Central

Bartoccioni, E; Gallucci, S; Scuderi, F; Ricci, E; Servidei, S; Broccolini, A; Tonali, P

1994-01-01

We investigated the relationship between the MHC-I, MHC-II and intercellular adhesion molecule-1 (ICAM-1) expression on myofibres and the presence of inflammatory cells in muscle specimens of 18 patients with inflammatory myopathies (nine polymyositis, seven dermatomyositis, two inclusion body myositis). We observed MHC-I expression in muscle fibres, infiltrating mononuclear cells and endothelial cells in every specimen. In seven patients, some muscle fibres were MHC-II-positive for the DR antigen, while the DP and DQ antigens were absent. ICAM-1 expression, detected in seven patients, was found in clusters of myofibres, associated with a marked MHC-I positivity and a widespread mononuclear infiltration. Most of the ICAM-1-positive fibres were regenerating fibres. Furthermore, some fibres expressed both ICAM-1 and DR antigens near infiltrating cells. This finding could support the hypothesis that myofibres may themselves be the site of autosensitization. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7507012

O-GlcNAc modification of Sp1 mediates hyperglycaemia-induced ICAM-1 up-regulation in endothelial cells.

PubMed

Zhang, Yuan; Qu, Yuan; Niu, Tian; Wang, Haiyan; Liu, Kun

2017-02-26

Intracellular adhesion molecule 1 (ICAM-1) is an important inflammatory factor that causes retinal damage during diabetic retinopathy. Hyperglycaemia can increase ICAM-1 expression in endothelial cells and the ICAM-1 promoter is responsive to the transcription factor specificity protein 1 (Sp1). O-GlcNAc modification is driven by the glucose concentration and has a profound effect on Sp1 activity. In this study, we investigated the underlying mechanism through which hyperglycaemia triggers ICAM-1 expression, which is mediated by O-GlcNAc modification of Sp1 in human umbilical vein endothelial cells (HUVECs) and rat retinal capillary endothelial cells (RRCECs). We showed that hyperglycaemia (30 mM) increased ICAM-1 expression compared to control conditions (5 mM). The addition of an OGT inhibitor decreased ICAM-1 expression and addition of an OGA inhibitor enhanced ICAM-1 expression. Furthermore, cells transduced with siSp1 exhibited dramatically decreased ICAM-1 expression. These results proved that the up-regulation of ICAM-1 with hyperglycaemia is mediated by O-GlcNAc modification of Sp1. It helps to explain the mechanism of ICAM-1 processing in HUVECs and RRCECs. Understanding how this inflammatory factor is modulated during diabetic retinopathy will ultimately help to design novel therapeutics to treat this condition. Copyright © 2017. Published by Elsevier Inc.

Elevated levels of serum sICAM-1 in asphyxiated low birth weight newborns

PubMed Central

Huseynova, Saadat; Panakhova, Nushaba; Orujova, Pusta; Hasanov, Safikhan; Guliyev, Mehman; Orujov, Agil

2014-01-01

Perinatal hypoxia results in neuronal and endothelial cell damage. The main purpose of this study was to investigate the correlation of soluble intercellular adhesion molecule 1 (sICAM-1) expression and peripheral blood changes in perinatal asphyxia with neuronal injury markers in low birth weight (LBW) neonates. We compared the concentrations of serum sICAM-1, neuron-specific enolase (NSE) and antibodies specific for NR2 glutamate receptors in 29 asphyxiated and 20 control infants using standard enzyme immunoassay procedures. The mean total concentrations of sICAM-1 and neuron-specific proteins (NSE and NR2-specific antibodies) were higher in the asphyxiated infants than in the control infants. The serum sICAM-1 concentrations significantly correlated with Apgar scoring and with the pH and lactate data from capillary or arterial cord blood. No significant correlation between serum concentrations of neuron specific proteins and blood changes of asphyxia was found. Therefore, endothelial sICAM-1 expression levels might be accepted as an indicator of the severity of perinatal asphyxia in LBW infants. PMID:25358349

Tumourigenicity and radiation resistance of mesenchymal stem cells.

PubMed

D'Andrea, Filippo P; Horsman, Michael R; Kassem, Moustapha; Overgaard, Jens; Safwat, Akmal

2012-05-01

Cancer stem cells are believed to be more radiation resistant than differentiated tumour cells of the same origin. It is not known, however, whether normal nontransformed adult stem cells share the same radioresistance as their cancerous counterpart. Nontumourigenic (TERT4) and tumourigenic (TRET20) cell lines, from an immortalised mesenchymal stem cell line, were grown in culture prior to irradiation and gene expression analysis. Radiation resistance was measured using a clonogenic assay. Differences in gene expression between the two cell lines, both under nontreated and irradiated conditions, were assessed with microarrays (Affymetrix Human Exon 1.0 ST array). The cellular functions affected by the altered gene expressions were assessed through gene pathway mapping (Ingenuity Pathway Analysis). Based on the clonogenic assay the nontumourigenic cell line was found to be more sensitive to radiation than the tumourigenic cell line. Using the exon chips, 297 genes were found altered between untreated samples of the cell lines whereas only 16 genes responded to radiation treatment. Among the genes with altered expression between the untreated samples were PLAU, PLAUR, TIMP3, MMP1 and LOX. The pathway analysis based on the alteration between the untreated samples indicated cancer and connective tissue disorders. This study has shown possible common genetic events linking tumourigenicity and radiation response. The PLAU and PLAUR genes are involved in apoptosis evasion while the genes TIMP3, MMP1 and LOX are involved in regulation of the surrounding matrix. The first group may contribute to the difference in radiation resistance observed and the latter could be a major contributor to the tumourigenic capabilities by degrading the intercellular matrix. These results also indicate that cancer stem cells are more radiation resistant than stem cells of the same origin.

Serum ICAM-1 level and ICAM-1 gene 1462A>G (K469E) polimorphism on microalbuminuria in nondiabetic, nonhypertensive and normolipidemic obese patients: Genetical background of microalbuminuria in obesity.

PubMed

Atay, Ahmet Engin; Esen, Bennur; Akbas, Halit; Gokmen, Emel Saglam; Pilten, Saadet; Guler, Hale; Yavuz, Dilek Gogas

A growing body of evidence suggest that obese individuals are under risk of renal parenchymal disorders when compared to nonobese counterparts. Microalbuminuria is the early marker of renal involvement. Although most of obese patients carries multiple risk factors for microalbuminuria, some obese individuals without risk factor may progress to microalbuminuria. The present study was performed to examine the role of ICAM-1 gene 1462A>G (K469E) polymorphism on microalbuminuria in obese subjects without diabetes mellitus, hypertension, hiperlipidemia and older age. Ninety eight obese and 96 nonobese individuals without a comorbidity enrolled into the study. Serum ICAM-1 level was measured by enzyme linked immunoabsorbent assay (ELISA) method. ICAM-1 gene 1462A>G (K469E) polymorphism was examined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Nepholometric method was used to examine urinary albumin loss, and microalbuminuria was measured by albumin to creatinine ratio. Obese individuals had significantly higher microalbuminuria and proteinuria level compared to nonobese subjects (p: 0.043 and p: 0.011; respectively). GG genotype of ICAM-1 carriers have significantly higher microalbuminuria compared to individuals with AA or AG genotype carriers (p: 0.042). Serum ICAM-1 level was significantly correlated with creatinine and microalbuminuria (p: 0.002 and p: 0.03; respectively). Logistic regression analysis indicated a 7.39 fold increased risk of microalbuminuria in individuals with GG genotype of ICAM-1 gene 1462A>G (K469E) polymorphism. GG genotype of ICAM-1 gene K469E polymorphism is associated with increased microalbuminuria in obese individuals without another metabolic risk factor. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Levels of sVCAM-1 and sICAM-1 in patients with lyme disease.

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Sobczyk-Krupiarz, Iwona; Salamon, Dominika; Garlicki, Aleksander; Mach, Tomasz

2009-04-01

Lyme disease is a multi-organ animal-borne disease caused by the spirochete Borrelia burgdorferi (Bb). As the pathogenesis of Lyme borreliosis is not fully understood, the study has been designed to examine levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum and the cerebrospinal fluid (CSF) of patients with Lyme borreliosis and their associations with clinical signs and symptoms and anti-Borrelia burgdorferi (anti-Bb) antibody titers. Sixty-four patients were enrolled in the study, including 39 patients treated for Lyme borreliosis and 25 without the disease (control group). In both groups sVCAM-1 and sICAM-1 levels were determined in serum and the CSF. Mean serum sICAM-1 and sVCAM-1 levels were higher in patients with Lyme borreliosis than in the control group. Serum sICAM-1 levels were significantly lower among patients with results positive for immunoglobulin M seroreactivity with Bb than among those with negative antibody responses. In patients with Bb-specific serum immunoglobulin G (IgG) antibodies, significantly higher serum sICAM-1 levels were found. Higher sVCAM-1 and sICAM-1 levels in the CSF were observed in patients positive for anti-Bb IgG antibody titers in the CSF. In patients with Lyme borreliosis, endothelial cell activation results in elevated levels of sICAM-1 and sVCAM-1 in serum and the CSF.

Isolation of Radiation-Resistant Bacteria from Mars Analog Antarctic Dry Valleys by Preselection, and the Correlation between Radiation and Desiccation Resistance.

PubMed

Musilova, Michaela; Wright, Gary; Ward, John M; Dartnell, Lewis R

2015-12-01

Extreme radiation-resistant microorganisms can survive doses of ionizing radiation far greater than are present in the natural environment. Radiation resistance is believed to be an incidental adaptation to desiccation resistance, as both hazards cause similar cellular damage. Desert soils are, therefore, promising targets to prospect for new radiation-resistant strains. This is the first study to isolate radiation-resistant microbes by using gamma-ray exposure preselection from the extreme cold desert of the Antarctic Dry Valleys (a martian surface analogue). Halomonads, identified by 16S rRNA gene sequencing, were the most numerous survivors of the highest irradiation exposures. They were studied here for the first time for both their desiccation and irradiation survival characteristics. In addition, the association between desiccation and radiation resistance has not been investigated quantitatively before for a broad diversity of microorganisms. Thus, a meta-analysis of scientific literature was conducted to gather a larger data set. A strong correlation was found between desiccation and radiation resistance, indicating that an increase in the desiccation resistance of 5 days corresponds to an increase in the room-temperature irradiation survival of 1 kGy. Irradiation at -79°C (representative of average martian surface temperatures) increases the microbial radiation resistance 9-fold. Consequently, the survival of the cold-, desiccation-, and radiation-resistant organisms isolated here has implications for the potential habitability of dormant or cryopreserved life on Mars. Extremophiles-Halomonas sp.-Antarctica-Mars-Ionizing radiation-Cosmic rays.

An Analysis of the Binding Characteristics of a Panel of Recently Selected ICAM-1 Binding Plasmodium falciparum Patient Isolates

PubMed Central

Madkhali, Aymen M.; Alkurbi, Mohammed O.; Szestak, Tadge; Bengtsson, Anja; Patil, Pradeep R.; Wu, Yang; Alharthi, Saeed; Jensen, Anja T. R.; Pleass, Richard; Craig, Alister G.

2014-01-01

The basis of severe malaria pathogenesis in part includes sequestration of Plasmodium falciparum-infected erythrocytes (IE) from the peripheral circulation. This phenomenon is mediated by the interaction between several endothelial receptors and one of the main parasite-derived variant antigens (PfEMP1) expressed on the surface of the infected erythrocyte membrane. One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive. The current study examined the cytoadherence patterns of lab-adapted patient isolates after selecting on ICAM-1. We investigated the binding phenotypes using variant ICAM-1 proteins including ICAM-1Ref, ICAM-1Kilifi, ICAM-1S22/A, ICAM-1L42/A and ICAM-1L44/A using static assays. The study also examined ICAM-1 blocking by four anti-ICAM-1 monoclonal antibodies (mAb) under static conditions. We also characterised the binding phenotypes using Human Dermal Microvascular Endothelial Cells (HDMEC) under flow conditions. The results show that different isolates have variant-specific binding phenotypes under both static and flow conditions, extending our previous observations that this variation might be due to variable contact residues on ICAM-1 being used by different parasite PfEMP1 variants. PMID:25360558

Optical imaging of radiation-induced metabolic changes in radiation-sensitive and resistant cancer cells

NASA Astrophysics Data System (ADS)

Alhallak, Kinan; Jenkins, Samir V.; Lee, David E.; Greene, Nicholas P.; Quinn, Kyle P.; Griffin, Robert J.; Dings, Ruud P. M.; Rajaram, Narasimhan

2017-06-01

Radiation resistance remains a significant problem for cancer patients, especially due to the time required to definitively determine treatment outcome. For fractionated radiation therapy, nearly 7 to 8 weeks can elapse before a tumor is deemed to be radiation-resistant. We used the optical redox ratio of FAD/(FAD+NADH) to identify early metabolic changes in radiation-resistant lung cancer cells. These radiation-resistant human A549 lung cancer cells were developed by exposing the parental A549 cells to repeated doses of radiation (2 Gy). Although there were no significant differences in the optical redox ratio between the parental and resistant cell lines prior to radiation, there was a significant decrease in the optical redox ratio of the radiation-resistant cells 24 h after a single radiation exposure (p=0.01). This change in the redox ratio was indicative of increased catabolism of glucose in the resistant cells after radiation and was associated with significantly greater protein content of hypoxia-inducible factor 1 (HIF-1α), a key promoter of glycolytic metabolism. Our results demonstrate that the optical redox ratio could provide a rapid method of determining radiation resistance status based on early metabolic changes in cancer cells.

ICAM-1 expression and organization in human endothelial cells is sensitive to gravity

NASA Astrophysics Data System (ADS)

Zhang, Yu; Sang, Chen; Paulsen, Katrin; Arenz, Andrea; Zhao, Ziyan; Jia, Xiaoling; Ullrich, Oliver; Zhuang, Fengyuan

2010-11-01

Transendothelial migration (TEM) of immune cells is a crucial process during a multitude of physiological and pathological conditions such as development, defense against infections and wound healing. Migration within the body tissues and through endothelial barriers is strongly dependent and regulated both by cytoskeletal processes and by expression of surface adhesion molecules such as ICAM-1 and VCAM-1. Space flight experiments have confirmed that TEM will be inhibited and may cause astronauts' immune function decreased and make them easy for infection. We used NASA RCCS to provide a simulated microgravity environment; endothelial cells were cultured on microcarrier beads and activated by TNF-α. Results demonstrate after clinorotation ICAM-1 expression increased, consistent with the notion in parabolic flights. However, VCAM-1 showed no significant change between activated or inactivated cells. Depolymerization of F-actin and clustering of ICAM-1 on cell membrane were also observed in short-term simulated microgravity, and after 24 h clinorotation, actin fiber rearrangement was initiated and clustering of ICAM-1 became stable. ICAM-1 mRNA and VCAM-1 mRNA were up-regulated after 30 min clinorotation, and returned to the same level with controls after 24 h clinorotation.

Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis.

PubMed

Kuessel, L; Wenzl, R; Proestling, K; Balendran, S; Pateisky, P; Yotova; Yerlikaya, G; Streubel, B; Husslein, H

2017-04-01

Do cell adhesion molecules play a role in endometriosis, and can they be used as a biomarker for diagnosing endometriosis? Altered expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endometrium and peritoneum may play a key role in endometriosis and the soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker. Cell adhesion molecules are cell surface proteins that mediate cellular adherence, inflammatory and immune responses, and cancer-related biological processes. Altered expression of VCAM-1 and ICAM-1 in women with endometriosis has been investigated previously; however, gene expression levels in tissues and protein levels in the serum have not been investigated in the same patients. We performed a prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent a laparoscopy for benign gynecological pathology in a university-based tertiary referral center for endometriosis. From a total of 138 women who were included in the study from July 2013 through September 2014, 97 had not received hormonal treatment for at least 3 months prior to recruitment and were included in the analysis; 49 (50.5%) of these women had endometriosis, and the 48 (49.5%) who did not have endometriosis served as a control group. During laparoscopy, tissue samples were obtained from ectopic and eutopic endometrium, and from normal pelvic peritoneum. In addition, serum samples were collected immediately before and 6-10 weeks after surgery. The mRNA levels of VCAM-1, ICAM-1 and epithelial cell adhesion molecule (EpCAM) were measured using quantitative real-time PCR, and serum protein levels of soluble VCAM-1 (sVCAM-1), ICAM-1 (sICAM-1) and EpCAM (sEpCAM) were measured using ELISA and correlated with endometriosis status. The mRNA levels of both VCAM-1 and ICAM-1 were higher in ectopic endometriotic lesions than in eutopic endometrium (P < 0.001). Moreover, the mRNA levels of both VCAM-1 and ICAM-1

Effect of antisense oligodeoxynucleotides for ICAM-1 on renal ischaemia–reperfusion injury in the anaesthetised rat

PubMed Central

Kiew, Lik Voon; Munavvar, Abdul Sattar; Law, Chung Hiong; Azizan, Abdullah Nor; Nazarina, Abdul Rahman; Sidik, Khalifah; Johns, Edward J

2004-01-01

An antisense oligodeoxynucleotide (As-ODN) to the 3′ untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia–reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin–As-ODN (As-ODN group), lipofectin–reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia–reperfusion injury. PMID:15047774

Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.

PubMed

Schellhorn, Melina; Haustein, Maria; Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

2015-11-17

The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, rofecoxib, valdecoxib), was found to cause a substantial upregulation of ICAM-1 protein levels. Likewise, ICAM-1 mRNA expression was increased by celecoxib. Celecoxib enhanced the susceptibility of cancer cells to be lysed by LAK cells with the respective effect being reversed by a neutralizing ICAM-1 antibody. In addition, enhanced killing of celecoxib-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen 1 (LFA-1), suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. Finally, celecoxib elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate celecoxib-induced upregulation of ICAM-1 on lung cancer cells to be responsible for intercellular ICAM-1/LFA-1 crosslink that confers increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of celecoxib.

Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1

PubMed Central

Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

2015-01-01

The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, rofecoxib, valdecoxib), was found to cause a substantial upregulation of ICAM-1 protein levels. Likewise, ICAM-1 mRNA expression was increased by celecoxib. Celecoxib enhanced the susceptibility of cancer cells to be lysed by LAK cells with the respective effect being reversed by a neutralizing ICAM-1 antibody. In addition, enhanced killing of celecoxib-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen 1 (LFA-1), suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. Finally, celecoxib elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate celecoxib-induced upregulation of ICAM-1 on lung cancer cells to be responsible for intercellular ICAM-1/LFA-1 crosslink that confers increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of celecoxib. PMID:26513172

Integrated Computer-Aided Manufacturing (ICAM) Architecture Part 2. Volume 6. Dynamics Modeling Manual (IDEF2)

DTIC Science & Technology

1981-06-01

design of manufacturing systems, "ilidation and verification of ICAM modules, integration of ICAM modules and the orderly transition of ICAM modules into...Function Model of "Manufacture Product" (MFGO) VIII - Composite Function Model of " Design Product" (DESIGNO) IX - Composite Information Model of...User Interface Requirements; and the Architecture of Design . This work was performed during the period of 29 September 1978 through 10

HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells

PubMed Central

Tabet, Fatiha; Vickers, Kasey C.; Cuesta Torres, Luisa F.; Wiese, Carrie B.; Shoucri, Bassem M.; Lambert, Gilles; Catherinet, Claire; Prado-Lourenco, Leonel; Levin, Michael G.; Thacker, Seth; Sethupathy, Praveen; Barter, Philip J.; Remaley, Alan T.; Rye, Kerry-Anne

2014-01-01

High-density lipoproteins (HDL) have many biological functions, including reducing endothelial activation and adhesion molecule expression. We recently reported that HDL transport and deliver functional microRNAs (miRNA). Here we show that HDL suppresses expression of intercellular adhesion molecule 1 (ICAM-1) through the transfer of miR-223 to endothelial cells. After incubation of endothelial cells with HDL, mature miR-223 levels are significantly increased in endothelial cells and decreased on HDL. However, miR-223 is not transcribed in endothelial cells and is not increased in cells treated with HDL from miR-223−/− mice. HDL inhibit ICAM-1 protein levels, but not in cells pretreated with miR-223 inhibitors. ICAM-1 is a direct target of HDL-transferred miR-223 and this is the first example of an extracellular miRNA regulating gene expression in cells where it is not transcribed. Collectively, we demonstrate that HDL’s anti-inflammatory properties are conferred, in part, through HDL-miR-223 delivery and translational repression of ICAM-1 in endothelial cells. PMID:24576947

Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction.

PubMed

Yan, Meiping; Zhang, Xinhua; Chen, Ao; Gu, Wei; Liu, Jie; Ren, Xiaojiao; Zhang, Jianping; Wu, Xiaoxiong; Place, Aaron T; Minshall, Richard D; Liu, Guoquan

2017-11-01

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells and initiates subsequent signaling that promotes their transendothelial migration (TEM). Vascular endothelial (VE)-cadherin plays a critical role in endothelial cell-cell adhesion, thereby controlling endothelial permeability and leukocyte transmigration. This study aimed to determine the molecular signaling events that originate from the ICAM-1-mediated firm adhesion of neutrophils that regulate VE-cadherin's role as a negative regulator of leukocyte transmigration. We observed that ICAM-1 interacts with Src homology domain 2-containing phosphatase-2 (SHP-2), and SHP-2 down-regulation via silencing of small interfering RNA in endothelial cells enhanced neutrophil adhesion to endothelial cells but inhibited neutrophil transmigration. We also found that VE-cadherin associated with the ICAM-1-SHP-2 complex. Moreover, whereas the activation of ICAM-1 leads to VE-cadherin dissociation from ICAM-1 and VE-cadherin association with actin, SHP-2 down-regulation prevented ICAM-1-VE-cadherin association and promoted VE-cadherin-actin association. Furthermore, SHP-2 down-regulation in vivo promoted LPS-induced neutrophil recruitment in mouse lung but delayed neutrophil extravasation. These results suggest that SHP-2- via association with ICAM-1-mediates ICAM-1-induced Src activation and modulates VE-cadherin switching association with ICAM-1 or actin, thereby negatively regulating neutrophil adhesion to endothelial cells and enhancing their TEM.-Yan, M., Zhang, X., Chen, A., Gu, W., Liu, J., Ren, X., Zhang, J., Wu, X., Place, A. T., Minshall, R. D., Liu, G. Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction. © FASEB.

Flame-retardant EPDM compounds containing phenanthrene to enhance radiation resistance

NASA Astrophysics Data System (ADS)

Chen, Jian; Huang, Wei; Jiang, Shu-Bin; Li, Xiao-Yan; An, You; Li, Chuang; Gao, Xiao-Ling; Chen, Hong-Bing

2017-01-01

Ethylene propylene diene monomer (EPDM) compounds with good flame-retardant and γ-ray radiation resistant properties were prepared by adding complex flame retardants and phenathrene. The resultant EPDM formulations have a long time to ignition (TTI >46 s), a low peak heat release rate (PHRR 341 kW/m2) and a high limited oxygen index (LOI >30). Effects of γ-ray radiation on the resultant flame-retardant EPDM was investigated. The formulated EPDM is a crosslinking dominated polymer under γ-ray radiation. The γ-ray radiation resistant property of EPDM was enhanced by adding phenanthrene. Elongation at break of EPDM formulated with phenanthrene could retain 91% after being irradiated to 0.3 MGy and still retains 40% elongation even after being irradiated to 0.9 MGy, which is much better the control. It is expected that the formulated flame-retardant and radiation resistant EPDM materials could meet the requirements for use in radiation environments.

Isolation of Radiation-Resistant Bacteria from Mars Analog Antarctic Dry Valleys by Preselection, and the Correlation between Radiation and Desiccation Resistance

PubMed Central

Wright, Gary; Ward, John M.; Dartnell, Lewis R.

2015-01-01

Abstract Extreme radiation–resistant microorganisms can survive doses of ionizing radiation far greater than are present in the natural environment. Radiation resistance is believed to be an incidental adaptation to desiccation resistance, as both hazards cause similar cellular damage. Desert soils are, therefore, promising targets to prospect for new radiation-resistant strains. This is the first study to isolate radiation-resistant microbes by using gamma-ray exposure preselection from the extreme cold desert of the Antarctic Dry Valleys (a martian surface analogue). Halomonads, identified by 16S rRNA gene sequencing, were the most numerous survivors of the highest irradiation exposures. They were studied here for the first time for both their desiccation and irradiation survival characteristics. In addition, the association between desiccation and radiation resistance has not been investigated quantitatively before for a broad diversity of microorganisms. Thus, a meta-analysis of scientific literature was conducted to gather a larger data set. A strong correlation was found between desiccation and radiation resistance, indicating that an increase in the desiccation resistance of 5 days corresponds to an increase in the room-temperature irradiation survival of 1 kGy. Irradiation at −79°C (representative of average martian surface temperatures) increases the microbial radiation resistance 9-fold. Consequently, the survival of the cold-, desiccation-, and radiation-resistant organisms isolated here has implications for the potential habitability of dormant or cryopreserved life on Mars. Key Words: Extremophiles—Halomonas sp.—Antarctica—Mars—Ionizing radiation—Cosmic rays. Astrobiology 15, 1076–1090. PMID:26684506

Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells.

PubMed

Dorecka, Mariola; Siemianowicz, Krzysztof; Francuz, Tomasz; Garczorz, Wojciech; Chyra, Agnieszka; Klych, Agnieszka; Romaniuk, Wanda

2013-01-01

Advanced glycation end products (AGEs) take part in the development of diabetic retinopathy. Hyperglycemia triggers an inflammatory response in the retina. These mechanisms may lead to an enhanced expression of adhesion molecules (ICAM-1 and VCAM-1) in human retinal pigment epithelium (HRPE). Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone with antidiabetogenic properties. GLP-1 also possesses vasoprotective properties. The aim of our study was to evaluate the influence of glycated albumin (GlyAlb; 100; 500 and 1000 mg/l) and pro-inflammatory cytokine, TNF-α (2.5 and 10 ng/ml), on expression of RAGE, ICAM-1 and VCAM-1 and to evaluate the influence of GLP-1 (100 nM) and its analogue, exendin-4 (10 nM), on the expression of RAGE, ICAM-1 and VCAM-1 in stimulated HRPE. TNF-α increased RAGE expression in HRPE cells. The addition of GlyAlb (500 and 1000 mg/l) resulted in a decrease of RAGE expression. Both TNF-α and GlyAlb increased the secretion of both adhesion molecules. In cells co-treated with GLP-1 or exendin-4 both incretins decreased RAGE expression in TNF-α treated cells, and in GlyAlb group. The ICAM-1 expression was lowered by exendin-4 and GLP-1 in cells stimulated by TNF-α and GlyAlb. The similar results were obtained for VCAM-1. All observed alterations were statistically significant. The obtained results indicate that both GLP-1 and exendin-4 by decreasing the expression of RAGE in HRPE can make these cells more resistant to circulating AGEs, and decreased expression of circulating VCAM-1 and ICAM-1, can be the result of anti-inflammatory properties of incretins and decreased expression of RAGE.

Resistance of Marine Bacterioneuston to Solar Radiation

PubMed Central

Agogué, Hélène; Joux, Fabien; Obernosterer, Ingrid; Lebaron, Philippe

2005-01-01

A total of 90 bacterial strains were isolated from the sea surface microlayer (i.e., bacterioneuston) and underlying waters (i.e., bacterioplankton) from two sites of the northwestern Mediterranean Sea. The strains were identified by sequence analysis, and growth recovery was investigated after exposure to simulated solar radiation. Bacterioneuston and bacterioplankton isolates were subjected to six different exposure times, ranging from 0.5 to 7 h of simulated noontime solar radiation. Following exposure, the growth of each isolate was monitored, and different classes of resistance were determined according to the growth pattern. Large interspecific differences among the 90 marine isolates were observed. Medium and highly resistant strains accounted for 41% and 22% of the isolates, respectively, and only 16% were sensitive strains. Resistance to solar radiation was equally distributed within the bacterioneuston and bacterioplankton. Relative contributions to the highly resistant class were 43% for γ-proteobacteria and 14% and 8% for α-proteobacteria and the Cytophaga/Flavobacterium/Bacteroides (CFB) group, respectively. Within the γ-proteobacteria, the Pseudoalteromonas and Alteromonas genera appeared to be highly resistant to solar radiation. The majority of the CFB group (76%) had medium resistance. Our study further provides evidence that pigmented bacteria are not more resistant to solar radiation than nonpigmented bacteria. PMID:16151115

Peptides based on alphaV-binding domains of erythrocyte ICAM-4 inhibit sickle red cell-endothelial interactions and vaso-occlusion in the microcirculation.

PubMed

Kaul, Dhananjay K; Liu, Xiao-du; Zhang, Xiaoqin; Mankelow, Tosti; Parsons, Stephen; Spring, Frances; An, Xiuli; Mohandas, Narla; Anstee, David; Chasis, Joel Anne

2006-11-01

Growing evidence shows that adhesion molecules on sickle erythrocytes interact with vascular endothelium leading to vaso-occlusion. Erythrocyte intercellular adhesion molecule-4 (ICAM-4) binds alphaV-integrins, including alphaVbeta3 on endothelial cells. To explore the contribution of ICAM-4 to vascular pathology of sickle cell disease, we tested the effects of synthetic peptides, V(16)PFWVRMS (FWV) and T(91)RWATSRI (ATSR), based on alphaV-binding domains of ICAM-4 and capable of inhibiting ICAM-4 and alphaV-binding in vitro. For these studies, we utilized an established ex vivo microvascular model system that enables intravital microscopy and quantitation of adhesion under shear flow. In this model, the use of platelet-activating factor, which causes endothelial oxidant generation and endothelial activation, mimicked physiological states known to occur in sickle cell disease. Infusion of sickle erythrocytes into platelet-activating factor-treated ex vivo rat mesocecum vasculature produced pronounced adhesion of erythrocytes; small-diameter venules were sites of maximal adhesion and frequent blockage. Both FWV and ATSR peptides markedly decreased adhesion, and no vessel blockage was observed with either of the peptides, resulting in improved hemodynamics. ATSR also inhibited adhesion in unactivated microvasculature. Although infused fluoresceinated ATSR colocalized with vascular endothelium, pretreatment with function-blocking antibody to alphaVbeta3-integrin markedly inhibited this interaction. Our data strengthen the thesis that ICAM-4 on sickle erythrocytes binds endothelium via alphaVbeta3 and that this interaction contributes to vaso-occlusion. Thus peptides or small molecule mimetics of ICAM-4 may have therapeutic potential.

Impacts of ICAM-1 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

PubMed

Wang, Shian-Shiang; Hsieh, Ming-Ju; Ou, Yen-Chuan; Chen, Chuan-Shu; Li, Jian-Ri; Hsiao, Pei-Ching; Yang, Shun-Fa

2014-08-01

Intercellular adhesion molecule (ICAM)-1, a cell adhesion molecule, is reportedly overexpressed in several cancers and may contribute to tumorgenesis and metastasis. The current study explored the effect of ICAM-1 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC) and the clinicopathological status. A total of 558 participants, including 279 healthy people and 279 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms of the ICAM-1 gene were assessed by a real-time polymerase chain reaction with the TaqMan assay. After adjusting for other covariants, the individuals carrying at least one G allele at ICAM-1 rs5498 had a 1.603-fold risk of developing UCC than did wild-type (AA) carriers. Furthermore, UCC patients who carried at least one G allele at rs5498 had a higher invasive stage risk (p < 0.05) than did patients carrying the wild-type allele. In conclusion, the rs5498 polymorphic genotypes of ICAM-1 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with ICAM-1 variants in carcinogenesis of UCC in Taiwan.

Utilization of SRNL-developed radiation-resistant polymer in high radiation environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skibo, A.

The radiation-resistant polymer developed by the Savannah River National Laboratory is adaptable for multiple applications to enhance polymer endurance and effectiveness in radiation environments. SRNL offers to collaborate with TEPCO in evaluation, testing, and utilization of SRNL’s radiation-resistant polymer in the D&D of the Fukushima Daiichi NPS. Refinement of the scope and associated costs will be conducted in consultation with TECPO.

Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria.

PubMed

Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

2017-04-01

A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compensate for the genome-destabilizing effect of environmental DNA damage and may be expected to result in a more conserved gene order in radiation-resistant species. However, here we show that rates of genome rearrangements, measured as loss of gene order conservation with time, are higher in radiation-resistant species in multiple, phylogenetically independent groups of bacteria. Comparison of indicators of selection for genome organization between radiation-resistant and phylogenetically matched, nonresistant species argues against tolerance to disruption of genome structure as a strategy for radiation resistance. Interestingly, an important mechanism affecting genome rearrangements in prokaryotes, the symmetrical inversions around the origin of DNA replication, shapes genome structure of both radiation-resistant and nonresistant species. In conclusion, the opposing effects of environmental DNA damage and DNA repair result in elevated rates of genome rearrangements in radiation-resistant bacteria. Copyright © 2017 Repar et al.

Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.

PubMed

Haustein, Maria; Ramer, Robert; Linnebacher, Michael; Manda, Katrin; Hinz, Burkhard

2014-11-15

Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study addressed the impact of cannabinoid-induced ICAM-1 on cancer cell adhesion to lymphokine-activated killer (LAK) cells and LAK cell-mediated cytotoxicity. Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently be lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody. Increased cancer cell lysis by CBD was likewise abrogated when CBD-induced ICAM-1 expression was blocked by specific siRNA or by antagonists to cannabinoid receptors (CB1, CB2) and to transient receptor potential vanilloid 1. In addition, enhanced killing of CBD-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen-1 (LFA-1) suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC) and R(+)-methanandamide (MA), a hydrolysis-stable endocannabinoid analogue. Finally, each cannabinoid elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less pronounced (CBD, THC) or absent (MA) ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of cannabinoids. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of TLR2 S450S and ICAM1 K469E polymorphisms with polycystic ovary syndrome (PCOS) and obesity.

PubMed

Ojeda-Ojeda, Miriam; Martínez-García, M Ángeles; Alpañés, Macarena; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2016-02-01

Toll-like receptors (TLRs) are activated by inflammatory stimuli and influence endothelial functions, contributing to the pathogenesis of atherosclerosis. We investigate the influence of polymorphisms in the genes encoding toll-like receptor 2 (TLR2) and 4 (TLR4) and endothelial adhesion molecules on polycystic ovary syndrome (PCOS) and its interaction with obesity. Ten single nucleotide polymorphisms were genotyped in 305 women with PCOS and 166 non-hyperandrogenic control women. In obese women, TLR2 S450S and ICAM1 K469E polymorphisms differently influenced metabolic variables and PCOS, respectively. Irrespective of PCOS, variant alleles of TLR2 S450S increased triglycerides, fasting insulin levels, and insulin resistance in obese women. TLR2 S450S interacted with obesity and PCOS on androstenedione levels, mutant alleles were associated with increased androstenedione concentrations in all women, with the exception of obese patients with PCOS (P=0.034). Regarding ICAM1 K469E, homozygosis for K469 alleles was more frequent in PCOS, but only in obese women (P=0.014). K469 alleles were also related to increased body mass index (P=0.017) and diastolic blood pressure (P=0.034). Moreover, ICAM1 K469E interacted with obesity and PCOS on serum triglyceride levels (P=0.019) and with PCOS on serum sex hormone-binding globulin concentrations (P=0.006). In conclusion, TLR2 S450S and ICAM1 K469E polymorphisms may be associated with PCOS and metabolic comorbidities in obese women. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of Culture Media on the Radiation Resistance of Micrococcus radiodurans

PubMed Central

Krabbenhoft, K. L.; Anderson, A. W.; Elliker, P. R.

1967-01-01

The addition of NZ-case (a tryptic digest of casein) to a growth medium (PC) consisting of tryptone, glucose, and yeast extract caused a significant decrease in γ radiation resistance of Micrococcus radiodurans. The level of radiation resistance was inversely related to the concentration of NZ-case. The ld50 for this organism was approximately 700 krad when grown in tryptone, glucose, yeast extract, and dl-methionine (TGYM) broth, but it was approximately one-half as resistant when grown in a PC medium containing 0.5% NZ-case (PCNZ). The resistance to ultraviolet light was also reduced. Cultures transferred from PCNZ to TGYM media regained the high level of resistance. Images Fig. 2 Fig. 3 PMID:5340165

Radiation Resistance of Soil Azotobacter

PubMed Central

Vela, Gerard R.; Wyss, Orville

1965-01-01

Vela, Gerard R. (School of Aerospace Medicine, Brooks Air Force Base, Tex.), and Orville Wyss. Radiation resistance of soil Azotobacter. J. Bacteriol. 89:1280–1285. 1965.—Quantitative recovery of Azotobacter from soils subjected to γ-radiation from a cobalt-60 source showed the soil populations to be much more highly resistant than isolates from such cultures grown on laboratory media. Even in the encysted state, the laboratory populations were reduced 10,000-fold by exposure to 200 kr, whereas the soil populations were not measurably reduced by that dose. PMID:14292998

Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure.

PubMed

Li, Ping-Chia; Chen, Wen-Chung; Chang, Li-Ching; Lin, Shao-Chieh

2008-05-01

This study aimed to 1) assess whether substance P (SP) acts via neurokinin (NK)-1 and NK-2 receptors to stimulate neurogenic inflammation (indicated by formation of ICAM-1 expression and oxidative stress) following oil smoke exposure (OSE) in rats; and 2) determine if pretreatment with antioxidants ameliorates the deleterious effects of OSE. Rats were pretreated with NK-1 receptor antagonist CP-96345, NK-2 receptor antagonist SR-48968, vitamin C, or catechins. OSE was for 30-120 min. Rats were killed 0-8 h later. Total lung resistance (RL), airway smooth muscle activity (ASMA), lung ICAM-1 expression, neurogenic plasma extravasation (via India ink and Evans blue dye), bronchoalveolar lavage fluid SP concentrations, and reactive oxygen species formation [via lucigenin- and luminal-amplified chemiluminescence (CL)] were assessed. Lung histology was performed. SP concentrations increased significantly in nonpretreated rats following OSE in a dose-dependent manner. RL and total ASMA increased over time after OSE. Vitamin C and catechin pretreatments were associated with significantly reduced lucigenin CL 2 and 4 h after OSE. Pretreatment with catechins significantly reduced luminal CL counts 4 and 8 h after OSE. Evans blue levels were significantly reduced following 60 and 120 min of OSE in catechin- and CP-96345-pretreated rats. ICAM-1 protein expression was significantly decreased in all pretreatment groups after OSE. Thickening of the alveolar capillary membrane, focal hemorrhaging, interstitial pneumonitis, and peribronchiolar inflammation were apparent in OSE lungs. These findings suggest that SP acts via the NK-1 receptor to provoke neurogenic inflammation, oxidative stress, and ICAM-1 expression after OSE in rats.

Extreme Ionizing-Radiation-Resistant Bacterium

NASA Technical Reports Server (NTRS)

Vaishampayan, Parag A.; Venkateswaran, Kasthuri J.; Schwendner, Petra

2012-01-01

There is a growing concern that desiccation and extreme radiation-resistant, non-spore-forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequent proliferation on another solar body. Such forward contamination would jeopardize future life detection or sample return technologies. The prime focus of NASA s planetary protection efforts is the development of strategies for inactivating resistance-bearing microorganisms. Eradification techniques can be designed to target resistance-conferring microbial populations by first identifying and understanding their physiologic and biochemical capabilities that confers its elevated tolerance (as is being studied in Deinococcus phoenicis, as a result of this description). Furthermore, hospitals, food, and government agencies frequently use biological indicators to ensure the efficacy of a wide range of radiation- based sterilization processes. Due to their resistance to a variety of perturbations, the non-spore forming D. phoenicis may be a more appropriate biological indicator than those currently in use. The high flux of cosmic rays during space travel and onto the unshielded surface of Mars poses a significant hazard to the survival of microbial life. Thus, radiation-resistant microorganisms are of particular concern that can survive extreme radiation, desiccation, and low temperatures experienced during space travel. Spore-forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate these extreme conditions. Since the Viking era, spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Members of the non-spore-forming bacterial community such as Deinococcus radiodurans can survive acute exposures to ionizing radiation (5 kGy), ultraviolet light (1 kJ/sq m), and desiccation (years). These resistive phenotypes of Deinococcus enhance the

Extreme Ionizing-Radiation-Resistant Bacterium

NASA Technical Reports Server (NTRS)

Vaishampayan, Parag A.; Venkateswaran, Kasthuri J.; Schwendner, Petra

2013-01-01

There is a growing concern that desiccation and extreme radiation-resistant, non-spore-forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequent proliferation on another solar body. Such forward contamination would jeopardize future life detection or sample return technologies. The prime focus of NASA s planetary protection efforts is the development of strategies for inactivating resistance-bearing micro-organisms. Eradi cation techniques can be designed to target resistance-conferring microbial populations by first identifying and understanding their physiologic and biochemical capabilities that confers its elevated tolerance (as is being studied in Deinococcus phoenicis, as a result of this description). Furthermore, hospitals, food, and government agencies frequently use biological indicators to ensure the efficacy of a wide range of radiation-based sterilization processes. Due to their resistance to a variety of perturbations, the nonspore forming D. phoenicis may be a more appropriate biological indicator than those currently in use. The high flux of cosmic rays during space travel and onto the unshielded surface of Mars poses a significant hazard to the survival of microbial life. Thus, radiation-resistant microorganisms are of particular concern that can survive extreme radiation, desiccation, and low temperatures experienced during space travel. Spore-forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate these extreme conditions. Since the Viking era, spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. Members of the non-sporeforming bacterial community such as Deinococcus radiodurans can survive acute exposures to ionizing radiation (5 kGy), ultraviolet light (1 kJ/m2), and desiccation (years). These resistive phenotypes of Deinococcus enhance the

Environmental Assessment and Monitoring with ICAMS (Image Characterization and Modeling System) Using Multiscale Remote-Sensing Data

NASA Technical Reports Server (NTRS)

Lam, N.; Qiu, H.-I.; Quattrochi, Dale A.; Zhao, Wei

1997-01-01

With the rapid increase in spatial data, especially in the NASA-EOS (Earth Observing System) era, it is necessary to develop efficient and innovative tools to handle and analyze these data so that environmental conditions can be assessed and monitored. A main difficulty facing geographers and environmental scientists in environmental assessment and measurement is that spatial analytical tools are not easily accessible. We have recently developed a remote sensing/GIS software module called Image Characterization and Modeling System (ICAMS) to provide specialized spatial analytical tools for the measurement and characterization of satellite and other forms of spatial data. ICAMS runs on both the Intergraph-MGE and Arc/info UNIX and Windows-NT platforms. The main techniques in ICAMS include fractal measurement methods, variogram analysis, spatial autocorrelation statistics, textural measures, aggregation techniques, normalized difference vegetation index (NDVI), and delineation of land/water and vegetated/non-vegetated boundaries. In this paper, we demonstrate the main applications of ICAMS on the Intergraph-MGE platform using Landsat Thematic Mapper images from the city of Lake Charles, Louisiana. While the utilities of ICAMS' spatial measurement methods (e.g., fractal indices) in assessing environmental conditions remain to be researched, making the software available to a wider scientific community can permit the techniques in ICAMS to be evaluated and used for a diversity of applications. The findings from these various studies should lead to improved algorithms and more reliable models for environmental assessment and monitoring.

ICAMs Redistributed by Chemokines to Cellular Uropods as a Mechanism for Recruitment of T Lymphocytes

PubMed Central

del Pozo, Miguel Angel; Cabañas, Carlos; Montoya, María C.; Ager, Ann; Sánchez-Mateos, Paloma; Sánchez-Madrid, Francisco

1997-01-01

The recruitment of leukocytes from the bloodstream is a key step in the inflammatory reaction, and chemokines are among the main regulators of this process. During lymphocyte–endothelial interaction, chemokines induce the polarization of T lymphocytes, with the formation of a cytoplasmic projection (uropod) and redistribution of several adhesion molecules (ICAM-1,-3, CD43, CD44) to this structure. Although it has been reported that these cytokines regulate the adhesive state of integrins in leukocytes, their precise mechanisms of chemoattraction remain to be elucidated. We have herein studied the functional role of the lymphocyte uropod. Confocal microscopy studies clearly showed that cell uropods project away from the cell bodies of adhered lymphocytes and that polarized T cells contact other T cells through the uropod structure. Time-lapse videomicroscopy studies revealed that uropod-bearing T cells were able, through this cellular projection, to contact, capture, and transport additional bystander T cells. Quantitative analysis revealed that the induction of uropods results in a 5–10-fold increase in cell recruitment. Uropod-mediated cell recruitment seems to have physiological relevance, since it was promoted by both CD45R0+ peripheral blood memory T cells as well as by in vivo activated lymphocytes. Additional studies showed that the cell recruitment mediated by uropods was abrogated with antibodies to ICAM-1, -3, and LFA-1, whereas mAb to CD43, CD44, CD45, and L-selectin did not have a significant effect, thus indicating that the interaction of LFA-1 with ICAM-1 and -3 appears to be responsible for this process. To determine whether the increment in cell recruitment mediated by uropod may affect the transendothelial migration of T cells, we carried out chemotaxis assays through confluent monolayers of endothelial cells specialized in lymphocyte extravasation. An enhancement of T cell migration was observed under conditions of uropod formation, and this

Endothelial microparticles reduce ICAM-1 expression in a microRNA-222-dependent mechanism

PubMed Central

Jansen, Felix; Yang, Xiaoyan; Baumann, Katharina; Przybilla, David; Schmitz, Theresa; Flender, Anna; Paul, Kathrin; Alhusseiny, Adil; Nickenig, Georg; Werner, Nikos

2015-01-01

Endothelial microparticles (EMP) are released from activated or apoptotic endothelial cells (ECs) and can be taken up by adjacent ECs, but their effect on vascular inflammation after engulfment is largely unknown. We sought to determine the role of EMP in EC inflammation. In vitro, EMP treatment significantly reduced tumour necrosis factor-α-induced endothelial intercellular adhesion molecule (ICAM)-1 expression on mRNA and protein level, whereas there was no effect on vascular cell adhesion molecule-1 expression. Reduced ICAM-1 expression after EMP treatment resulted in diminished monocyte adhesion in vitro. In vivo, systemic treatment of ApoE−/− mice with EMP significantly reduced murine endothelial ICAM-1 expression. To explore the underlying mechanisms, Taqman microRNA array was performed and microRNA (miR)-222 was identified as the strongest regulated miR between EMP and ECs. Following experiments demonstrated that miR-222 was transported into recipient ECs by EMP and functionally regulated expression of its target protein ICAM-1 in vitro and in vivo. After simulating diabetic conditions, EMP derived from glucose-treated ECs contained significantly lower amounts of miR-222 and showed reduced anti-inflammatory capacity in vitro and in vivo. Finally, circulating miR-222 level was diminished in patients with coronary artery disease (CAD) compared to patients without CAD. EMPs promote anti-inflammatory effects in vitro and in vivo by reducing endothelial ICAM-1 expression via the transfer of functional miR-222 into recipient cells. In pathological hyperglycaemic conditions, EMP-mediated miR-222-dependent anti-inflammatory effects are reduced. PMID:26081516

Structure-activity relationship of ortho- and meta-phenol based LFA-1 ICAM inhibitors.

PubMed

Lin, Edward Yin-Shiang; Guckian, Kevin M; Silvian, Laura; Chin, Donovan; Boriack-Sjodin, P Ann; van Vlijmen, Herman; Friedman, Jessica E; Scott, Daniel M

2008-10-01

LFA-1 ICAM inhibitors based on ortho- and meta-phenol templates were designed and synthesized by Mitsunobu chemistry. The selection of targets was guided by X-ray co-crystal data, and led to compounds which showed an up to 30-fold increase in potency over reference compound 1 in the LFA-1/ICAM1-Ig assay. The most active compound exploited a new hydrogen bond to the I-domain and exhibited subnanomolar potency.

Radiation-induced amorphization resistance and radiation tolerance in structurally related oxides.

PubMed

Sickafus, Kurt E; Grimes, Robin W; Valdez, James A; Cleave, Antony; Tang, Ming; Ishimaru, Manabu; Corish, Siobhan M; Stanek, Christopher R; Uberuaga, Blas P

2007-03-01

Ceramics destined for use in hostile environments such as nuclear reactors or waste immobilization must be highly durable and especially resistant to radiation damage effects. In particular, they must not be prone to amorphization or swelling. Few ceramics meet these criteria and much work has been devoted in recent years to identifying radiation-tolerant ceramics and the characteristics that promote radiation tolerance. Here, we examine trends in radiation damage behaviour for families of compounds related by crystal structure. Specifically, we consider oxides with structures related to the fluorite crystal structure. We demonstrate that improved amorphization resistance characteristics are to be found in compounds that have a natural tendency to accommodate lattice disorder.

Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia.

PubMed

Obi, Andrea T; Andraska, Elizabeth; Kanthi, Yogendra; Kessinger, Chase W; Elfline, Megan; Luke, Cathy; Siahaan, Teruna J; Jaffer, Farouc A; Wakefield, Thomas W; Henke, Peter K

2017-01-26

Venous thromboembolism is a major cause of death during and immediately post-sepsis. Venous thrombosis (VT) is mediated by cell adhesion molecules and leukocytes, including neutrophil extracellular traps (NETs). Sepsis, or experimentally, endotoxaemia, shares similar characteristics and is modulated via toll like receptor 4 (TLR4). This study was undertaken to determine if endotoxaemia potentiates early stasis thrombogenesis, and secondarily to determine the role of VT TLR4, ICAM-1 and neutrophils (PMNs). Wild-type (WT), ICAM-1 -/- and TLR4 -/- mice underwent treatment with saline or LPS (10 mg/kg i. p.) alone, or followed by inferior vena cava (IVC) ligation to generate stasis VT. In vivo microscopy of leukocyte trafficking was performed in non-thrombosed mice, and tissue and plasma were harvested during early VT formation. Pre-thrombosis, circulating ICAM-1 was elevated and increased leukocyte adhesion and rolling occurred on the IVC of LPS-treated mice. Post-thrombosis, endotoxaemic mice formed larger, platelet-poor thrombi. Endotoxaemic TLR4 -/- mice did not have an augmented thrombotic response and exhibited significantly decreased circulating ICAM-1 compared to endotoxaemic WT controls. Endotoxaemic ICAM-1 -/- mice had significantly smaller thrombi compared to controls. Hypothesising that PMNs localised to the inflamed endothelium were promoting thrombosis, PMN depletion using anti-Ly6G antibody was performed. Paradoxically, VT formed without PMNs was amplified, potentially related to endotoxaemia induced elevation of PAI-1 and circulating FXIII, and decreased uPA. Endotoxaemia enhanced early VT occurs in a TLR-4 and ICAM-1 dependent fashion, and is potentiated by neutropenia. ICAM-1 and/or TLR-4 inhibition may be a unique strategy to prevent sepsis-associated VT.

Enhanced radiation resistant fiber optics

DOEpatents

Lyons, P.B.; Looney, L.D.

1993-11-30

A process for producing an optical fiber having enhanced radiation resistance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation. 4 figures.

MicroSPECT imaging of triple negative breast cancer cell tumor xenografted in athymic mice with radioiodinated anti-ICAM-1 monoclonal antibody.

PubMed

You, Linyi; Wang, Xiangyu; Guo, Zhide; Zhang, Deliang; Zhang, Pu; Li, Jindian; Su, Xinhui; Pan, Weimin; Zhang, Xianzhong

2018-04-04

Intercellular adhesion molecule-1(ICAM-1) is a potential molecular target and biomarker for triple negative breast cancer (TNBC) therapy and diagnosis. In this study, aICAM-1 was radioiodinated with 125 I/ 131 I in high radiochemical yield and the probes for TNBC tumor targeting and radioimmunotherapy were evaluated in tumor-bearing mice. High and specific accumulation of 125 I-aICAM1 in TNBC MDA-MB-231 tumor was observed in SPECT imaging and the tumor grew was inhibited obviously by 131 I-aICAM1. Thus, the radioiodinated aICAM1 could serve as potential agents for TNBC theranostics. Copyright © 2018 Elsevier Ltd. All rights reserved.

IFN-gamma priming up-regulates IFN-stimulated gene factor 3 (ISGF3) components, augmenting responsiveness of IFN-resistant melanoma cells to type I IFNs.

PubMed

Wong, L H; Hatzinisiriou, I; Devenish, R J; Ralph, S J

1998-06-01

IFN-stimulated gene factor 3 (ISGF3) mediates transcriptional activation of IFN-sensitive genes (ISGs). The component subunits of ISGF3, STAT1alphabeta, STAT2, and p48-ISGF3gamma, are tyrosine phosphorylated before their assembly into a complex. Subsequently, the ISGF3 complex is translocated to the nucleus. We have recently established that the responsiveness of human melanoma cell lines to type I IFNs correlates directly with their intracellular levels of ISGF3 components, particularly STAT1. In the present study, we show that pretreating IFN-resistant melanoma cell lines with IFN-gamma (IFN-gamma priming) before stimulation with type I IFN also results in increased levels of ISGF3 components and enhanced DNA-binding activation of ISGF3. In addition, IFN-gamma priming of IFN-resistant melanoma cell lines increased expression of type I IFN-induced ISG products, including ISG54, 2'-5'-oligoadenylate synthase, HLA class I, B7-1, and ICAM-1 Ags. Furthermore, IFN-gamma priming enhanced the antiviral effect of IFN-beta on the IFN-resistant melanoma cell line, MM96. These results support a role for IFN-gamma priming in up-regulating ISGF3, thereby augmenting the responsiveness of IFN-resistant melanoma cell lines to type I IFN and providing a molecular basis and justification for using sequential IFN therapy, as proposed by others, to enhance the use of IFNs in the treatment of melanoma.

Inactivation of the Radiation-Resistant Spoilage Bacterium Micrococcus radiodurans

PubMed Central

Duggan, D. E.; Anderson, A. W.; Elliker, P. R.

1963-01-01

A simplified technique permitting the pipetting of raw puréed meats for quantitative bacteriological study is described for use in determining survival of these non-sporing bacteria, which are exceptionally resistant to radiation. Survival curves, using gamma radiation as the sterilizing agent, were determined in raw beef with four strains of Micrococcus radiodurans. Survival curves of the R1 strain in other meat substrates showed that survival was significantly greater in raw beef and raw chicken than in raw fish or in cooked beef. Resistance was lowest in the buffer. Cells grown in broth (an artificial growth medium) and resuspended in beef did not differ in resistance from cells that had been grown and irradiated in beef. Survival rate was statistically independent of the initial cell concentration, even though there appeared to be a correlation between lower death rate and lower initial cell concentrations. The initial viable count of this culture of the domesticated R1 strain in beef was reduced by a factor of about 10-5 by 3.0 megarad, and 4.0 megarad reduced the initial count by a factor of more than 10-9. Data suggest that M. radiodurans R1 is more resistant to radiation than spore-forming spoilage bacteria for which inactivation rates have been published. PMID:14063780

Endothelial microparticles reduce ICAM-1 expression in a microRNA-222-dependent mechanism.

PubMed

Jansen, Felix; Yang, Xiaoyan; Baumann, Katharina; Przybilla, David; Schmitz, Theresa; Flender, Anna; Paul, Kathrin; Alhusseiny, Adil; Nickenig, Georg; Werner, Nikos

2015-09-01

Endothelial microparticles (EMP) are released from activated or apoptotic endothelial cells (ECs) and can be taken up by adjacent ECs, but their effect on vascular inflammation after engulfment is largely unknown. We sought to determine the role of EMP in EC inflammation. In vitro, EMP treatment significantly reduced tumour necrosis factor-α-induced endothelial intercellular adhesion molecule (ICAM)-1 expression on mRNA and protein level, whereas there was no effect on vascular cell adhesion molecule-1 expression. Reduced ICAM-1 expression after EMP treatment resulted in diminished monocyte adhesion in vitro. In vivo, systemic treatment of ApoE-/- mice with EMP significantly reduced murine endothelial ICAM-1 expression. To explore the underlying mechanisms, Taqman microRNA array was performed and microRNA (miR)-222 was identified as the strongest regulated miR between EMP and ECs. Following experiments demonstrated that miR-222 was transported into recipient ECs by EMP and functionally regulated expression of its target protein ICAM-1 in vitro and in vivo. After simulating diabetic conditions, EMP derived from glucose-treated ECs contained significantly lower amounts of miR-222 and showed reduced anti-inflammatory capacity in vitro and in vivo. Finally, circulating miR-222 level was diminished in patients with coronary artery disease (CAD) compared to patients without CAD. EMPs promote anti-inflammatory effects in vitro and in vivo by reducing endothelial ICAM-1 expression via the transfer of functional miR-222 into recipient cells. In pathological hyperglycaemic conditions, EMP-mediated miR-222-dependent anti-inflammatory effects are reduced. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Synthesis and radiation resistance of fullerenes and fullerene derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shilin, V. A., E-mail: shilin@pnpi.spb.ru; Lebedev, V. T.; Sedov, V. P.

2016-07-15

The parameters of an electric-arc facility for the synthesis of fullerenes and endohedral metallofullerenes are optimized. The resistance of C{sub 60} and C{sub 70} fullerenes and C{sub 60}(OH){sub 30} and C{sub 70}(OH){sub 30} fullerenols against neutron irradiation is studied. It is established that the radiation resistance of the fullerenes is higher than that of the fullerenols, but the radiation resistance of the Gd@C{sub 2n} endometallofullerenes is lower than that of the corresponding Gd@C{sub 2n}(OH){sub 38} fullerenols. The radiation resistance of mixtures of Me@C{sub 2n}(OH){sub 38} (Me = Gd, Tb, Sc, Fe, and Pr) endometallofullerenes with C{sub 60}(OH){sub 30} is determined.more » The factors affecting the radiation resistance of the fullerenes and fullerenols are discussed.« less

INF-gamma rearranges membrane topography of MHC-I and ICAM-1 in colon carcinoma cells.

PubMed

Bacsó, Zsolt; Bene, László; Damjanovich, László; Damjanovich, Sándor

2002-01-18

Flow-cytometric fluorescence energy transfer (FCET) measurements between fluorescently labeled cell surface MHC-I and ICAM-1 molecules indicated similar receptor patterns in the plasma membrane of interferon-gamma (INF-gamma)-treated colon carcinoma cells as those observed earlier at the surface of lymphoid cells. INF-gamma activation significantly increased the density of MHC-I and ICAM-1 proteins in the membrane. This increase in receptor density was accompanied by decreased proximity level of the homo-associated MHC-I receptors. Hetero-association of MHC-I and ICAM-1 molecules was increased by INF-gamma treatment. INF-gamma changed neither hetero- nor homo-association of transferrin receptors. By staining the sphingomyelin/cholesterol-enriched lipid microdomains with fluorescently labeled cholera toxin B subunit, we found an increase in the amount of lipid-raft associated G(M1)-gangliosides due to INF-gamma treatment. Confocal microscopic results and FCET measurements show that MHC-I and ICAM-1 are components of G(M1)-ganglioside containing lipid-rafts and also support an increase in the size of these lipid-rafts upon INF-gamma treatment.

ICAM-1-Targeted Liposomes Loaded with Liver X Receptor Agonists Suppress PDGF-Induced Proliferation of Vascular Smooth Muscle Cells

NASA Astrophysics Data System (ADS)

Huang, Xu; Xu, Meng-Qi; Zhang, Wei; Ma, Sai; Guo, Weisheng; Wang, Yabin; Zhang, Yan; Gou, Tiantian; Chen, Yundai; Liang, Xing-Jie; Cao, Feng

2017-05-01

The proliferation of vascular smooth muscle cells (VSMCs) is one of the key events during the progress of atherosclerosis. The activated liver X receptor (LXR) signalling pathway is demonstrated to inhibit platelet-derived growth factor BB (PDGF-BB)-induced VSMC proliferation. Notably, following PDGF-BB stimulation, the expression of intercellular adhesion molecule-1 (ICAM-1) by VSMCs increases significantly. In this study, anti-ICAM-1 antibody-conjugated liposomes were fabricated for targeted delivery of a water-insoluble LXR agonist (T0901317) to inhibit VSMC proliferation. The liposomes were prepared by filming-rehydration method with uniform size distribution and considerable drug entrapment efficiency. The targeting effect of the anti-ICAM-T0901317 liposomes was evaluated by confocal laser scanning microscope (CLSM) and flow cytometry. Anti-ICAM-T0901317 liposomes showed significantly higher inhibition effect of VSMC proliferation than free T0901317 by CCk8 proliferation assays and BrdU staining. Western blot assay further confirmed that anti-ICAM-T0901317 liposomes inhibited retinoblastoma (Rb) phosphorylation and MCM6 expression. In conclusion, this study identified anti-ICAM-T0901317 liposomes as a promising nanotherapeutic approach to overcome VSMC proliferation during atherosclerosis progression.

Circulating soluble adhesion molecules in patients with giant cell arteritis. Correlation between soluble intercellular adhesion molecule-1 (sICAM-1) concentrations and disease activity

PubMed Central

Coll-Vinent, B.; Vilardell, C.; Font, C.; Oristrell, J.; Hernandez-Rodrigu..., J.; Yague, J.; Urbano-Marquez, A.; Grau, J.; Cid, M.

1999-01-01

OBJECTIVE—To evaluate whether changes in concentrations of circulating adhesion molecules are related to disease activity in patients with giant cell arteritis (GCA).
METHODS—A sandwich ELISA was used to measure soluble intercellular adhesion molecule-1 (sICAM-1), sICAM-3, vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), and L-selectin (sL-selectin) in serum and plasma samples from patients with GCA. A cross sectional study was performed on 64 GCA patients at different activity stages and on 35 age and sex matched healthy donors. Thirteen of these patients were evaluated at the time of diagnosis and serially during follow up.
RESULTS—At the time of diagnosis, sICAM-1 concentrations were significantly higher in active GCA patients than in controls (mean (SD) 360.55 (129.78) ng/ml versus 243.25 (47.43) ng/ml, p<0.001). In contrast, sICAM-3, sVCAM-1, sE-selectin, and sL-selectin values did not differ from those obtained in normal donors. With corticosteroid administration, a decrease in sICAM-1 concentrations was observed, reaching normal values when clinical remission was achieved (263.18 (92.7) ng/ml globally, 293.59 (108.39) ng/ml in the group of patients in recent remission, and 236.83 (70.02) ng/ml in those in long term remission). In the 13 patients followed up longitudinally, sICAM-1 values also normalised with clinical remission (225.87 (64.25) ng/ml in patients in recent remission, and 256.29 (75.15) ng/ml in those in long term remission).
CONCLUSIONS—Circulating sICAM-1 concentrations clearly correlate with clinically apparent disease activity in GCA patients. Differences with results previously found in patients with other vasculitides may indicate that different pathogenic mechanisms contribute to vascular inflammation in different disorders.

 Keywords: adhesion molecules; giant cell arteritis; inflammation PMID:10364919

Acid Sphingomyelinase-Derived Ceramide Regulates ICAM-1 Function during T Cell Transmigration across Brain Endothelial Cells.

PubMed

Lopes Pinheiro, Melissa A; Kroon, Jeffrey; Hoogenboezem, Mark; Geerts, Dirk; van Het Hof, Bert; van der Pol, Susanne M A; van Buul, Jaap D; de Vries, Helga E

2016-01-01

Multiple sclerosis (MS) is a chronic demyelinating disorder of the CNS characterized by immune cell infiltration across the brain vasculature into the brain, a process not yet fully understood. We previously demonstrated that the sphingolipid metabolism is altered in MS lesions. In particular, acid sphingomyelinase (ASM), a critical enzyme in the production of the bioactive lipid ceramide, is involved in the pathogenesis of MS; however, its role in the brain vasculature remains unknown. Transmigration of T lymphocytes is highly dependent on adhesion molecules in the vasculature such as intercellular adhesion molecule-1 (ICAM-1). In this article, we hypothesize that ASM controls T cell migration by regulating ICAM-1 function. To study the role of endothelial ASM in transmigration, we generated brain endothelial cells lacking ASM activity using a lentiviral shRNA approach. Interestingly, although ICAM-1 expression was increased in cells lacking ASM activity, we measured a significant decrease in T lymphocyte adhesion and consequently transmigration both in static and under flow conditions. As an underlying mechanism, we revealed that upon lack of endothelial ASM activity, the phosphorylation of ezrin was perturbed as well as the interaction between filamin and ICAM-1 upon ICAM-1 clustering. Functionally this resulted in reduced microvilli formation and impaired transendothelial migration of T cells. In conclusion, in this article, we show that ASM coordinates ICAM-1 function in brain endothelial cells by regulating its interaction with filamin and phosphorylation of ezrin. The understanding of these underlying mechanisms of T lymphocyte transmigration is of great value to develop new strategies against MS lesion formation. Copyright © 2015 by The American Association of Immunologists, Inc.

Ras Labs.-CASIS-ISS NL experiment for synthetic muscle: resistance to ionizing radiation

NASA Astrophysics Data System (ADS)

Rasmussen, Lenore; Sandberg, Eric; Albers, Leila N.; Rodriguez, Simone; Gentile, Charles A.; Meixler, Lewis D.; Ascione, George; Hitchner, Robert; Taylor, James; Hoffman, Dan; Cylinder, David; Moy, Leon; Mark, Patrick S.; Prillaman, Daniel L.; Nordarse, Robert; Menegus, Michael J.; Ratto, Jo Ann; Thellen, Christopher; Froio, Danielle; Furlong, Cosme; Razavi, Payam; Valenza, Logan; Hablani, Surbhi; Fuerst, Tyler; Gallucci, Sergio; Blocher, Whitney; Liffland, Stephanie

2016-04-01

In anticipation of deep space travel, new materials are being explored to assist and relieve humans in dangerous environments, such as high radiation, extreme temperature, and extreme pressure. Ras Labs Synthetic Muscle - electroactive polymers (EAPs) that contract and expand at low voltages - which mimic the unique gentle-yet-strong nature of human tissue, is a potential asset to manned space travel through protective gear and human assist robotics and for unmanned space exploration through deep space. Generation 3 Synthetic Muscle was proven to be resistant to extreme temperatures, and there were indications that these materials may also be radiation resistant. The purpose of the Ras Labs-CASIS-ISS Experiment is to test the radiation resistivity of the third and fourth generation of these EAPs, as well as to make them even more radiation resistant or radiation hardened. On Earth, exposure of the Generation 3 and Generation 4 EAPs to a Cs-137 radiation source for 47.8 hours with a total dose of 305.931 kRad of gamma radiation was performed at the US Department of Energy's Princeton Plasma Physics Laboratory (PPPL) at Princeton University, followed by pH, peroxide, Shore Hardness Durometry, and electroactivity testing to determine the inherent radiation resistivity of these contractile EAPs and to determine whether the EAPs could be made even more radiation resistant through the application of appropriate additives and coatings. The on Earth preliminary tests determined that selected Ras Labs EAPs were not only inherently radiation resistant, but with the appropriate coatings and additives, could be made even more radiation resistant. Gforce testing to over 10 G's was performed at US Army's ARDEC Labs, with excellent results, in preparation for space flight to the International Space Station National Laboratory (ISS-NL). Selected samples of Generation 3 and Generation 4 Synthetic Muscle™, with various additives and coatings, were launched to the ISS-NL on April

Expression, production, and renaturation of a functional single-chain variable antibody fragment (scFv) against human ICAM-1

PubMed Central

Sun, H.; Wu, G.M.; Chen, Y.Y.; Tian, Y.; Yue, Y.H.; Zhang, G.L.

2014-01-01

Intercellular adhesion molecule-1 (ICAM-1) is an important factor in the progression of inflammatory responses in vivo. To develop a new anti-inflammatory drug to block the biological activity of ICAM-1, we produced a monoclonal antibody (Ka=4.19×10−8 M) against human ICAM-1. The anti-ICAM-1 single-chain variable antibody fragment (scFv) was expressed at a high level as inclusion bodies in Escherichia coli. We refolded the scFv (Ka=2.35×10−7 M) by ion-exchange chromatography, dialysis, and dilution. The results showed that column chromatography refolding by high-performance Q Sepharose had remarkable advantages over conventional dilution and dialysis methods. Furthermore, the anti-ICAM-1 scFv yield of about 60 mg/L was higher with this method. The purity of the final product was greater than 90%, as shown by denaturing gel electrophoresis. Enzyme-linked immunosorbent assay, cell culture, and animal experiments were used to assess the immunological properties and biological activities of the renatured scFv. PMID:24919171

MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression in inflammatory myopathies.

PubMed

Bartoccioni, E; Gallucci, S; Scuderi, F; Ricci, E; Servidei, S; Broccolini, A; Tonali, P

1994-01-01

We investigated the relationship between the MHC-I, MHC-II and intercellular adhesion molecule-1 (ICAM-1) expression on myofibres and the presence of inflammatory cells in muscle specimens of 18 patients with inflammatory myopathies (nine polymyositis, seven dermatomyositis, two inclusion body myositis). We observed MHC-I expression in muscle fibres, infiltrating mononuclear cells and endothelial cells in every specimen. In seven patients, some muscle fibres were MHC-II-positive for the DR antigen, while the DP and DQ antigens were absent. ICAM-1 expression, detected in seven patients, was found in clusters of myofibres, associated with a marked MHC-I positivity and a widespread mononuclear infiltration. Most of the ICAM-1-positive fibres were regenerating fibres. Furthermore, some fibres expressed both ICAM-1 and DR antigens near infiltrating cells. This finding could support the hypothesis that myofibres may themselves be the site of autosensitization.

Evolution of radiation resistance in a complex microenvironment

NASA Astrophysics Data System (ADS)

Kim, So Hyun; Austin, Robert; Mehta, Monal; Kahn, Atif

2013-03-01

Radiation treatment responses in brain cancers are typically associated with short progression-free intervals in highly lethal malignancies such as glioblastomas. Even as patients routinely progress through second and third line salvage therapies, which are usually empirically selected, surprisingly little information exists on how cancer cells evolve resistance. We will present experimental results showing how in the presence of complex radiation gradients evolution of resistance to radiation occurs. Sponsored by the NCI/NIH Physical Sciences Oncology Centers

Radiation resistant austenitic stainless steel alloys

DOEpatents

Maziasz, Philip J.; Braski, David N.; Rowcliffe, Arthur F.

1989-01-01

An austenitic stainless steel alloy, with improved resistance to radiation-induced swelling and helium embrittlement, and improved resistance to thermal creep at high temperatures, consisting essentially of, by weight percent: from 16 to 18% nickel; from 13 to 17% chromium; from 2 to 3% molybdenum; from 1.5 to 2.5% manganese; from 0.01 to 0.5% silicon; from 0.2 to 0.4% titanium; from 0.1 to 0.2% niobium; from 0.1 to 0.6% vanadium; from 0.06 to 0.12% carbon; from 0.01% to 0.03% nitrogen; from 0.03 to 0.08% phosphorus; from 0.005 to 0.01% boron; and the balance iron, and wherein the alloy may be thermomechanically treated to enhance physical and mechanical properties.

Transmigrated neutrophils in the intestinal lumen engage ICAM 1 to regulate the epithelial barrier and neutrophil recruitment

PubMed Central

Sumagin, Ronen; Robin, Alex Z.; Nusrat, Asma; Parkos, Charles A.

2014-01-01

Neutrophil (PMN) transepithelial migration (TEM) and accumulation in luminal spaces is a hallmark of mucosal inflammation. TEM has been extensively modeled, however the functional consequences and molecular basis of PMN interactions with luminal epithelial ligands are not clear. Here we report that cytokine-induced expression of a PMN ligand, intercellular adhesion molecule-1 (ICAM-1), exclusively on the luminal (apical) membrane of the intestinal epithelium results in accumulation and enhanced motility of transmigrated PMN on the apical epithelial surface. Using complementary in-vitro and in-vivo approaches we demonstrate that ligation of epithelial ICAM-1 by PMN or with specific antibodies results in myosin light chain kinase (MLCK)-dependent increases in epithelial permeability that are associated with enhanced PMN TEM. Effects of ICAM-1 ligation on epithelial permeability and PMN migration in-vivo were blocked after intraluminal addition of peptides derived from the cytoplasmic domain of ICAM-1. These findings provide new evidence for functional interactions between PMN and epithelial cells after migration into the intestinal lumen. While such interactions may aid in clearance of invading microorganisms by promoting PMN recruitment, engagement of ICAM-1 under pathologic conditions would increase accumulation of epithelial-associated PMN, thus contributing to mucosal injury as observed in conditions including ulcerative colitis. PMID:24345805

ICAM-1, ELAM-1, TNF-alpha and IL-6 in serum and blister liquid of pemphigus vulgaris patients.

PubMed

Alecu, M; Alecu, S; Coman, G; Gălăţescu, E; Ursaciuc, C

1999-01-01

The levels of ICAM-1, ELAM-1, TNF-alpha and IL-6 were determined in 12 patients with pemphigus vulgaris (PV) both in serum and the blister liquid. As a control, the same parameters were determined in 7 patients with herpes zoster (HZ). The patients with PV presented significantly higher values of ICAM-1 in the blister liquid, as compared to the serum values. The values of TNF-alpha and IL-6 were increased both in serum and the blister liquid. The ELAM-1 values did not show significant differences between serum and the blister liquid. In HZ patients, the blister liquid values did not significantly exceed the serum values both for ICAM-1 and ELAM-1. TNF-alpha and IL-6 presented high values both in serum and the blister liquid. We consider that the high values of ICAM-1 in the blister liquid from PV patients suggest the involvement of this adhesion molecule in the PV pathogenic features. The implication of ICAM-1 could be nonspecific and limited, and could possibly represent a reaction to the destruction of the desmosomal bonds within keratinocytes.

Glycyrrhetinic acid inhibits ICAM-1 expression via blocking JNK and NF-κB pathways in TNF-α-activated endothelial cells

PubMed Central

Chang, Ying-ling; Chen, Chien-lin; Kuo, Chao-Lin; Chen, Bor-chyuan; You, Jyh-sheng

2010-01-01

Aim: To investigate the effects of glycyrrhetinic acid (GA), an active component extracted from the root of Glycyrrhizae glabra, on the expression of intercellular adhesion molecule-1 (ICAM-1) in tumor necrosis factor-α (TNF-α)-activated human umbilical vein endothelial cells (HUVEC). Methods: ICAM-1 mRNA and protein levels were detected using RT-PCR and cell enzyme-linked immunosorbent assays. The adherence of human monocytic THP-1 cells labeled with [3H]thymidine to HUVEC was determined by counting radioactivity with a scintillation counter. The activation of mitogen-activated protein kinases as well as the degradation of IκB and nuclear factor-κB (NF-κB) or phospho-c-Jun in the nucleus were detected by western blots. NF-κB binding activity was detected using electrophoretic mobility shift assay. Results: GA (50 and 100 μmol/L) significantly inhibits TNF-α-induced ICAM-1 mRNA and protein expressions, as well as THP-1 cell adhesiveness in HUVEC. GA selectively inhibited TNF-α-activated signal pathway of c-Jun N-terminal kinase (JNK), without affecting extracellular signal-regulated kinase 1/2 and p38. Furthermore, GA apparently inhibited IκB/NF-κB signaling system by preventing IκB degradation, NF-κB translocation, and NF-κB/DNA binding activity. Finally, pretreatment with GA or the inhibitors of NF-κB, JNK, and p38 reduced the ICAM-1 protein expression induced by TNF-α. Conclusion: GA inhibits TNF-α-stimulated ICAM-1 expression, leading to a decrease in adherent monocytes to HUVEC. This inhibition is attributed to GA interruption of both JNK/c-Jun and IκB/NF-κB signaling pathways, which decrease activator protein-1 (AP-1) and NF-κB mediated ICAM-1 expressions. The results suggest that GA may provide a beneficial effect in treating vascular diseases associated with inflammation, such as atherosclerosis. PMID:20418897

Dietary intake and cardiometabolic biomarkers in relation to insulin resistance and hypertension in a middle-aged and elderly population in Beijing, China.

PubMed

Wang, Jia; Hong, Zhongxin; Wu, Li; Ding, Bingjie; Bi, Yanxia; Gu, Zhongyi; Li, Wei

2017-08-01

This study investigated the relationships of dietary intake and cardiometabolic biomarkers with insulin resistance and hypertension in rural middle-aged and elderly people in China. One hundred and eight middle-aged and elderly adults were recruited in Zhangfang village in May 2014. We measured blood pressure, anthropometric parameters, and biochemical indexes, including high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), glucose, insulin, and blood lipids. Homeostasis model assessment of insulin resistance index (HOMA-IR) was assessed on the basis of fasting glucose and insulin. We recorded participant demographic characteristics, dietary intake, and lifestyle using questionnaires. Hypertensive participants had higher levels of triglycerides (TG), hsCRP, sICAM-1, body fat percentage (BF%), arm muscle circumference (AMC) and HOMA-IR than nonhypertensive individuals. Hypertensive participants had higher carbohydrate intake but lower intakes of protein and fat. Carbohydrate intake was positively correlated with hsCRP, sICAM-1, TG, BF%, and HOMA-IR, and was negatively correlated with AMC. Protein and fat intakes were negatively correlated with hsCRP and sICAM-1. Protein intake was also significantly negatively correlated with TG and HOMA-IR, and positively correlated with AMC. HOMA-IR was positively correlated with hsCRP, sICAM-1, TG and BF%, and negatively correlated with AMC. Multivariable linear regression indicated that TG, sICAM-1, and hsCRP were significantly associated with HOMA-IR. In conclusion, in a rural Chinese population, high intake of carbohydrate and low intake of fat and protein were associated with insulin resistance and hypertension, possibly by increasing inflammatory factors such as sICAM-1 and hsCRP, increasing BF% and increasing the level of plasma TG.

Increased radiation resistance in lithium-counterdoped silicon solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.; Mehta, S.

1984-01-01

Lithium-counterdoped n(+)p silicon solar cells are found to exhibit significantly increased radiation resistance to 1-MeV electron irradiation when compared to boron-doped n(+)p silicon solar cells. In addition to improved radiation resistance, considerable damage recovery by annealing is observed in the counterdoped cells at T less than or equal to 100 C. Deep level transient spectroscopy measurements are used to identify the defect whose removal results in the low-temperature aneal. It is suggested that the increased radiation resistance of the counterdoped cells is primarily due to interaction of the lithium with interstitial oxygen.

Radiation resistant austenitic stainless steel alloys

DOEpatents

Maziasz, P.J.; Braski, D.N.; Rowcliffe, A.F.

1987-02-11

An austenitic stainless steel alloy, with improved resistance to radiation-induced swelling and helium embrittlement, and improved resistance to thermal creep at high temperatures, consisting essentially of, by weight percent: from 16 to 18% nickel; from 13 to 17% chromium; from 2 to 3% molybdenum; from 1.5 to 2.5% manganese; from 0.01 to 0.5% silicon; from 0.2 to 0.4% titanium; from 0.1 to 0.2% niobium; from 0.1 to 0.6% vanadium; from 0.06 to 0.12% carbon; from 0.01 to 0.03% nitrogen; from 0.03 to 0.08% phosphorus; from 0.005 to 0.01% boron; and the balance iron, and wherein the alloy may be thermomechanically treated to enhance physical and mechanical properties. 4 figs.

Specific Binding, Uptake, and Transport of ICAM-1-Targeted Nanocarriers Across Endothelial and Subendothelial Cell Components of the Blood-Brain Barrier

PubMed Central

Hsu, Janet; Rappaport, Jeff; Muro, Silvia

2014-01-01

Purpose The blood-brain barrier (BBB) represents a target for therapeutic intervention and an obstacle for brain drug delivery. Targeting endocytic receptors on brain endothelial cells (ECs) helps transporting drugs and carriers into and across this barrier. While most receptors tested are associated with clathrin-mediated pathways, clathrin-independent routes are rather unexplored. We have examined the potential for one of these pathways, cell adhesion molecule (CAM)-mediated endocytosis induced by targeting intercellular adhesion molecule 1 (ICAM-1), to transport drug carriers into and across BBB models. Methods Model polymer nanocarriers (NCs) coated with control IgG or antibodies against ICAM-1 (IgG NCs vs. anti-ICAM NCs; ~250-nm) were incubated with human brain ECs, astrocytes (ACs), or pericytes (PCs) grown as monocultures or bilayered (endothelial+subendothelial) co-cultures. Results ICAM-1 was present and overexpressed in disease-like conditions on ECs and, at a lesser extent, on ACs and PCs which are BBB subendothelial components. Specific targeting and CAM-mediated uptake of anti-ICAM NCs occurred in these cells, although this was greater for ECs. Anti-ICAM NCs were transported across endothelial monolayers and endothelial+subendothelial co-cultures modeling the BBB. Conclusions CAM-mediated transport induced by ICAM-1 targeting operates in endothelial and subendothelial cellular components of the BBB, which may provide an avenue to overcome this barrier. PMID:24558007

Specific binding, uptake, and transport of ICAM-1-targeted nanocarriers across endothelial and subendothelial cell components of the blood-brain barrier.

PubMed

Hsu, Janet; Rappaport, Jeff; Muro, Silvia

2014-07-01

The blood-brain barrier (BBB) represents a target for therapeutic intervention and an obstacle for brain drug delivery. Targeting endocytic receptors on brain endothelial cells (ECs) helps transport drugs and carriers into and across this barrier. While most receptors tested are associated with clathrin-mediated pathways, clathrin-independent routes are rather unexplored. We have examined the potential for one of these pathways, cell adhesion molecule (CAM)-mediated endocytosis induced by targeting intercellular adhesion molecule -1 (ICAM-1), to transport drug carriers into and across BBB models. Model polymer nanocarriers (NCs) coated with control IgG or antibodies against ICAM-1 (IgG NCs vs. anti-ICAM NCs; ~250-nm) were incubated with human brain ECs, astrocytes (ACs), or pericytes (PCs) grown as monocultures or bilayered (endothelial+subendothelial) co-cultures. ICAM-1 was present and overexpressed in disease-like conditions on ECs and, at a lesser extent, on ACs and PCs which are BBB subendothelial components. Specific targeting and CAM-mediated uptake of anti-ICAM NCs occurred in these cells, although this was greater for ECs. Anti-ICAM NCs were transported across endothelial monolayers and endothelial+subendothelial co-cultures modeling the BBB. CAM-mediated transport induced by ICAM-1 targeting operates in endothelial and subendothelial cellular components of the BBB, which may provide an avenue to overcome this barrier.

Modulating Radiation Resistance: Novel Protection Paradigms Based on Defenses against Ionizing Radiation in the Extrempohile Deinococcus radiodurans

DTIC Science & Technology

2013-07-01

USA (2013); 2) Many environmental yeast are extremely radiation-resistant, accumulate nitrogenous Mn2+-Pi complexes, and highly resistant to...5 important in aerobic environments . Numerous organisms which accumulate “compatible solutes” fit this model, including representative archaea...cyanobacteria, lichens, alpine yeast, and tardigrades. 4.3 Knowns and Unknowns of Deinococcus Mn2+ Complexes It is worth reminding the reader

Bacterial and archaeal resistance to ionizing radiation

NASA Astrophysics Data System (ADS)

Confalonieri, F.; Sommer, S.

2011-01-01

Organisms living in extreme environments must cope with large fluctuations of temperature, high levels of radiation and/or desiccation, conditions that can induce DNA damage ranging from base modifications to DNA double-strand breaks. The bacterium Deinococcus radiodurans is known for its resistance to extremely high doses of ionizing radiation and for its ability to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Recently, extreme ionizing radiation resistance was also generated by directed evolution of an apparently radiation-sensitive bacterial species, Escherichia coli. Radioresistant organisms are not only found among the Eubacteria but also among the Archaea that represent the third kingdom of life. They present a set of particular features that differentiate them from the Eubacteria and eukaryotes. Moreover, Archaea are often isolated from extreme environments where they live under severe conditions of temperature, pressure, pH, salts or toxic compounds that are lethal for the large majority of living organisms. Thus, Archaea offer the opportunity to understand how cells are able to cope with such harsh conditions. Among them, the halophilic archaeon Halobacterium sp and several Pyrococcus or Thermococcus species, such as Thermococcus gammatolerans, were also shown to display high level of radiation resistance. The dispersion, in the phylogenetic tree, of radioresistant prokaryotes suggests that they have independently acquired radioresistance. Different strategies were selected during evolution including several mechanisms of radiation byproduct detoxification and subtle cellular metabolism modifications to help cells recover from radiation-induced injuries, protection of proteins against oxidation, an efficient DNA repair tool box, an original pathway of DNA double-strand break repair, a condensed nucleoid that may prevent the dispersion of the DNA fragments and specific radiation-induced proteins involved in

Radiation-resistant composite for biological shield of personnel

NASA Astrophysics Data System (ADS)

Barabash, D. E.; Barabash, A. D.; Potapov, Yu B.; Panfilov, D. V.; Perekalskiy, O. E.

2017-10-01

This article presents the results of theoretical and practical justification for the use of polymer concrete based on nonisocyanate polyurethanes in biological shield structures. We have identified the impact of ratio: polymer - radiation-resistant filling compound on the durability and protection properties of polymer concrete. The article expounds regression dependence of the change of basic properties of the aforementioned polymer concrete on the absorbed radiation dose rate. Synergy effect in attenuation of radioactivity release in case of conjoint use of hydrogenous polymer base and radiation-resistant powder is also addressed herein.

In situ study on surface roughening in radiation-resistant Ag nanowires

NASA Astrophysics Data System (ADS)

Shang, Z.; Li, Jin; Fan, C.; Chen, Y.; Li, Q.; Wang, H.; Shen, T. D.; Zhang, X.

2018-05-01

Metallic materials subjected to heavy ion irradiation experience significant radiation damage. Free surface is a type of effective defect sinks to improve the radiation resistance in metallic materials. However, the radiation resistance of metallic nanowires (NWs) is largely unknown. Here we show, via in situ Kr ion irradiations in a transmission electron microscope, Ag NWs exhibited much better radiation resistance than coarse-grained Ag. Irradiation-induced prominent surface roughening in Ag NWs provides direct evidence for interaction between defect clusters and free surface. Diameter dependent variation of the surface roughness in irradiated Ag NWs has also been observed. This study provides insight on mechanisms of enhanced radiation resistance via free surfaces in metallic NWs.

In situ study on surface roughening in radiation-resistant Ag nanowires.

PubMed

Shang, Z; Li, Jin; Fan, C; Chen, Y; Li, Q; Wang, H; Shen, T D; Zhang, X

2018-05-25

Metallic materials subjected to heavy ion irradiation experience significant radiation damage. Free surface is a type of effective defect sinks to improve the radiation resistance in metallic materials. However, the radiation resistance of metallic nanowires (NWs) is largely unknown. Here we show, via in situ Kr ion irradiations in a transmission electron microscope, Ag NWs exhibited much better radiation resistance than coarse-grained Ag. Irradiation-induced prominent surface roughening in Ag NWs provides direct evidence for interaction between defect clusters and free surface. Diameter dependent variation of the surface roughness in irradiated Ag NWs has also been observed. This study provides insight on mechanisms of enhanced radiation resistance via free surfaces in metallic NWs.

Comparative immunoexpression of ICAM-1, TGF-β1 and ki-67 in periapical and residual cysts

PubMed Central

Armada, Luciana; dos Santos, Teresa-Cristina; Pires, Fabio-Ramoa

2017-01-01

Background This study compared the immunohistochemical expression of ki-67, transforming growth factor beta 1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in inflammatory periapical cysts and residual cysts. Material and Methods The study sample was composed by 25 periapical cysts and 25 residual cysts and immunohistochemical reactions were carried out using antibodies directed against ICAM-1, TGF-β1 and ki-67. Clinical, radiological, gross, histological and immunohistochemical data were tabulated for descriptive and comparative analysis using the SPSS software and differences were considered statistically significant when p<0.05%. Results There were no differences between the expression of ICAM-1 (p=0.239) and TGF-β1 (p=0.258) when comparing both groups. Ki-67 labeling index was higher in residual cysts compared to periapical cysts (p=0.017). Conclusions Results from the present study suggest that some specific inflammatory stimuli on residual cysts would modulate their mechanisms of etiopathogenesis, growing and repair. Key words:Periapical cyst, radicular cyst, residual cyst, transforming growth factor beta 1 (TGF-β1), intercellular adhesion molecule 1 (ICAM-1), ki-67. PMID:27918735

RADIATION-INDUCED MUTATIONS FOR STEM RUST RESISTANCE IN OATS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konzak, C.F.

1959-01-01

Stem rust rcsistant viriants from earlier experiments on the induction or resistance in oats by radiation were found to result from natural field hybridization. Recent controlled experiments did, however, yield new variants at a low frequency in one instance. and no variants in another. Both experiments included over 3,000 lines from irradiated seeds. One previously unknown type of rust resistance reaction was obtained in a mutant plant. This mutant shows a temperature sensitive response for resistance to race 7A of Puccinia graminis avenae. It was suggested that some, as yet unknown, mcdifying factors mav limit the development of induced changesmore » into mutations. (auth)« less

ICAM-1 Binding Rhinoviruses A89 and B14 Uncoat in Different Endosomal Compartments

PubMed Central

Conzemius, Rick; Ganjian, Haleh; Blaas, Dieter

2016-01-01

ABSTRACT Human rhinovirus A89 (HRV-A89) and HRV-B14 bind to and are internalized by intercellular adhesion molecule 1 (ICAM-1); as demonstrated earlier, the RNA genome of HRV-B14 penetrates into the cytoplasm from endosomal compartments of the lysosomal pathway. Here, we show by immunofluorescence microscopy that HRV-A89 but not HRV-B14 colocalizes with transferrin in the endocytic recycling compartment (ERC). Applying drugs differentially interfering with endosomal recycling and with the pathway to lysosomes, we demonstrate that these two major-group HRVs productively uncoat in distinct endosomal compartments. Overexpression of constitutively active (Rab11-GTP) and dominant negative (Rab11-GDP) mutants revealed that uncoating of HRV-A89 depends on functional Rab11. Thus, two ICAM-1 binding HRVs are routed into distinct endosomal compartments for productive uncoating. IMPORTANCE Based on similarity of their RNA genomic sequences, the more than 150 currently known common cold virus serotypes were classified as species A, B, and C. The majority of HRV-A viruses and all HRV-B viruses use ICAM-1 for cell attachment and entry. Our results highlight important differences of two ICAM-1 binding HRVs with respect to their intracellular trafficking and productive uncoating; they demonstrate that serotypes belonging to species A and B, but entering the cell via the same receptors, direct the endocytosis machinery to ferry them along distinct pathways toward different endocytic compartments for uncoating. PMID:27334586

Radiation resistance of endohedral metallofullerenols under neutron irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Szhogina, A. A.; Shilin, V. A., E-mail: allin-ok2@mail.ru; Sedov, V. P.

2016-07-15

The endohedral metallofullerenols Me@C{sub 2n}(OH){sub 38–40} + C{sub 2n}(OH){sub 38–40} (Me = Tb, Sc, Gd, Fe, Pr, Mo) have been obtained and their radiation resistance under irradiation by a neutron flux of 8 × 10{sup 13} cm{sup –2} s{sup –1} has been studied. The factors affecting the radiation resistance of endohedral metallofullerenols are discussed.

Metal-nanotube composites as radiation resistant materials

NASA Astrophysics Data System (ADS)

González, Rafael I.; Valencia, Felipe; Mella, José; van Duin, Adri C. T.; So, Kang Pyo; Li, Ju; Kiwi, Miguel; Bringa, Eduardo M.

2016-07-01

The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role of nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.

Circulating sICAM-1 and sE-Selectin as biomarker of infection and prognosis in patients with systemic inflammatory response syndrome.

PubMed

de Pablo, Raúl; Monserrat, Jorge; Reyes, Eduardo; Díaz, David; Rodríguez-Zapata, Manuel; de la Hera, Antonio; Prieto, Alfredo; Álvarez-Mon, Melchor

2013-03-01

Vascular endothelium activation is a key pathogenic step in systemic inflammatory response syndrome (SIRS) that can be triggered by both microbial and sterile proinflammatory stimuli. The relevance of soluble adhesion molecules as clinical biomarkers to discriminate between infectious and non-infectious SIRS, and the individual patient prognosis, has not been established. We prospectively measured by sandwich ELISA, serum levels of soluble E-Selectin (sE-Selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble intercellular adhesion molecule-2 (sICAM-2) at ICU admission and at days 3, 7, 14 and 28 in patients with sepsis and at days 3 and 7 in patients with non-infectious SIRS. At ICU admission, sE-Selectin, sVCAM-1 and sICAM-1 in patients with infectious SIRS were significantly higher than those found in patients with non-infectious SIRS. ROC analysis revealed that the AUC for infection identification was best for sICAM-1 (0.900±0.041; 95% CI 0.819-0.981; p<0.0001). Moreover, multivariate analysis showed that 4 variables were significantly and independently associated with mortality at 28 days: male gender (OR 15.90; 95% CI, 2.54-99.32), MODS score (OR 5.60; 95% CI, 1.67-18.74), circulating sE-Selectin levels (OR 4.81; 95% CI, 1.34-17.19) and sVCAM-1 concentrations (OR 4.80; 95% CI, 1.34-17.14). Patients with SIRS secondary to infectious or non-infectious etiology show distinctive patterns of disturbance in serum soluble adhesion molecules. Serum ICAM-1 is a reliable biomarker for classifying patients with infectious SIRS from those with non-infectious SIRS. In addition, soluble E-Selectin is a prognostic biomarker with higher levels in patients with SIRS and fatal outcome. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Nanoparticle induced piezoelectric, super toughened, radiation resistant, multi-functional nanohybrids.

PubMed

Tiwari, Vimal K; Shripathi, T; Lalla, N P; Maiti, Pralay

2012-01-07

We have developed multifunctional nanohybrids of poly(vinylidene fluoride-co-chlorotrifluoroethylene) (CTFE) with a small percentage of surface modified inorganic layered silicate showing dramatic improvement in toughness, radiation resistant and piezoelectric properties vis-à-vis pristine polymer. Massive intercalation (d(001) 1.8 → 3.9 nm) of polymer inside the nanoclay galleries and unique crystallization behavior of the fluoropolymer on the surface of individual silicate layer has been reported. Toughness in the nanohybrid increases more than three orders of magnitude as compared to pure CTFE. High energy radiation (80 MeV Si(+7)) causes chain session, amorphization and creates olefinic bonds in the pure polymer while the nanohybrids are radiation resistant at a similar dose. Nanoclay induces the metastable piezoelectric β-phase in CTFE, suitable for sensor and actuator application. Molecular level changes after irradiation and controlled morphology for smart membrane have been confirmed by using spectroscopy, sol-gel technique, surface morphology studies and in situ residual gas analysis.

Increased ICAM-1 Expression in Transformed Human Oral Epithelial Cells: Molecular Mechanism and Functional Role in Peripheral Blood Mononuclear Cell Adhesion and Lymphokine-Activated-Killer Cell Cytotoxicity

PubMed Central

Huang, George T.-J.; Zhang, Xinli; Park, No-Hee

2012-01-01

The intercellular adhesion molecule-1 (ICAM-1, CD54) serves as a counter-receptor for the β2-integrins, LFA-1 and Mac-1, which are expressed on leukocytes. Although expression of ICAM-1 on tumor cells has a role in tumor progression and development, information on ICAM-1 expression and its role in oral cancer has not been established. Normal human oral keratinocytes (NHOK), human papilloma virus (HPV)-immortalized human oral keratinocyte lines (HOK-16B, HOK-18A, and HOK-18C), and six human oral neoplastic cell lines (HOK-16B-BaP-T1, SCC-4, SCC-9, HEp-2, Tu-177 and 1483) were used to study ICAM-1 expression and its functional role in vitro. Our results demonstrated that NHOK express negligible levels of ICAM-1, whereas immortalized human oral keratinocytes and cancer cells express significantly higher levels of ICAM-1, except for HOK-16B-BaP-T1 and HEp-2. Altered mRNA half-lives did not fully account for the increased accumulation of ICAM-1 mRNA. Adhesion of peripheral blood mononuclear cells (PBMC) to epithelial cells correlated with cell surface ICAM-1 expression levels. This adhesion was inhibited by antibodies specific for either ICAM-1 or LFA-1/Mac-1, suggesting a role for these molecules in adhesion. In contrast, lymphokine-activated-killer (LAK) cell cytotoxic killing of epithelial cells did not correlate with ICAM-1 levels or with adhesion. Nonetheless, within each cell line, blocking of ICAM-1 or LFA-1/Mac-1 reduced LAK cells killing, suggesting that ICAM-1 is involved in mediating this killing. PMID:10938387

Accumulation of Mn(II) in Deinococcus radiodurans Facilitates Gamma-Radiation Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daly, Michael J.; Gaidamakova, E; Matrosova, V

2004-11-05

Deinococcus radiodurans is extremely resistant to ionizing radiation. How this bacterium can grow under chronic gamma-radiation (50 Gy/hour) or recover from acute doses greater than 10 kGy is unknown. We show that D. radiodurans accumulates very high intracellular manganese and low iron levels compared to radiation sensitive bacteria, and resistance exhibits a concentration-dependent response to Mn(II). Among the most radiation-resistant bacterial groups reported, Deinococcus, Enterococcus, Lactobacillus and cyanobacteria spp. accumulate Mn(II). In contrast, Shewanella oneidensis and Pseudomonas putida have high Fe but low intracellular Mn concentrations and are very sensitive. We propose that Mn(II) accumulation facilitates recovery from radiation injury.

The interactive effects of genetic polymorphisms within LFA-1/ICAM-1/GSK-3β pathway and environmental hazards on the development of Graves' opthalmopathy.

PubMed

Yang, Ge; Fu, Yang; Lu, Xiaoyan; Wang, Menghua; Dong, Hongtao; Li, Qiuming

2018-05-22

The purpose of this investigation was to explore the combined effects of single nucleotide polymorphisms (SNPs) within LFA-1/ICAM-1/GSK-3β pathway and environmental hazards on susceptibility to Graves' opthalmopathy (GO) among a Chinese Han population. Altogether 305 GO patients and 283 Graves' disease (GD) subjects were recruited. Information relevant to the participants' age, gender, body mass index (BMI), regular physical activity, smoking history, alcohol intake, stressful work environment, stress at work, family history of thyroid disease and 131 I treatment were summarized, and the participants' related SNPs of LFA-1/ICAM-1/GSK-3β were also detected. Then the gene-gene and gene-environment interactions were evaluated by logistic regression model and multi-factor dimensionality reduction (MDR) modeling. The results exhibited that age, BMI, smoking history, stressful work, stress at home, family history of thyroid disease and 131 I treatment appeared as potential indicators regulating GO risk, when either univariate or multivariate regression analysis was performed (all P < 0.05). Moreover, rs12716977 (T > C) and rs2230433 (G > C) of LFA-1, rs1799969 (G > A) and rs5498 (A > G) of ICAM-1, as well as rs6438552 (T > C) and rs334558 (T > C) of GSK-3β were significantly associated with altered susceptibility to GO under the allelic models (all P < 0.05). Also haplotype TGAATC acted as a protective factor against GO risk (P < 0.05), whereas haplotype CGAACC largely elevated risk of GO (P < 0.05). Besides, logistic regression analysis demonstrated that rs12716927, rs5498 and rs6438552 all would affect the influences exerted by age, BMI, smoking history, stressful work, stress at home, family history of thyroid disease or 131 I treatment on GO susceptibility (all P < 0.05). MDR modeling implied that the combined model of rs12716977, rs2230433 and rs1799969 was the supreme interactive model when BMI was co-assessed, and the

I-domain of lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow.

PubMed

Eniola, A Omolola; Krasik, Ellen F; Smith, Lee A; Song, Gang; Hammer, Daniel A

2005-11-01

In their active state, beta(2)-integrins, such as LFA-1, mediate the firm arrest of leukocytes by binding intercellular adhesion molecules (ICAMs) expressed on endothelium. Although the primary function of LFA-1 is assumed to be the ability to mediate firm adhesion, recent work has shown that LFA-1 can contribute to cell tethering and rolling under hydrodynamic flow, a role previously largely attributed to the selectins. The inserted (I) domain of LFA-1 has recently been crystallized in the wild-type (wt) and locked-open conformations and has been shown to, respectively, support rolling and firm adhesion under flow when expressed in alpha(L)beta(2) heterodimers or as isolated domains on cells. Here, we report results from cell-free adhesion assays where wt I-domain-coated polystyrene particles were allowed to interact with ICAM-1-coated surfaces in shear flow. We show that wt I-domain can independently mediate the capture of particles from flow and support their rolling on ICAM-1 surfaces in a manner similar to how carbohydrate-selectin interactions mediate rolling. Adhesion is specific and blocked by appropriate antibodies. We also show that the rolling velocity of I-domain-coated particles depends on the wall shear stress in flow chamber, I-domain site density on microsphere surfaces, and ICAM-1 site density on substrate surfaces. Furthermore, we show that rolling is less sensitive to wall shear stress and ICAM-1 substrate density at high density of I-domain on the microsphere surface. Computer simulations using adhesive dynamics can recreate bead rolling dynamics and show that the mechanochemical properties of ICAM-1-I-domain interactions are similar to those of carbohydrate-selectin interactions. Understanding the biophysics of adhesion mediated by the I-domain of LFA-1 can elucidate the complex roles this integrin plays in leukocyte adhesion in inflammation.

Essential Role of Cofilin-1 in Regulating Thrombin-induced RelA/p65 Nuclear Translocation and Intercellular Adhesion Molecule 1 (ICAM-1) Expression in Endothelial Cells*

PubMed Central

Fazal, Fabeha; Bijli, Kaiser M.; Minhajuddin, Mohd; Rein, Theo; Finkelstein, Jacob N.; Rahman, Arshad

2009-01-01

Activation of RhoA/Rho-associated kinase (ROCK) pathway and the associated changes in actin cytoskeleton induced by thrombin are crucial for activation of NF-κB and expression of its target gene ICAM-1 in endothelial cells. However, the events acting downstream of RhoA/ROCK to mediate these responses remain unclear. Here, we show a central role of cofilin-1, an actin-binding protein that promotes actin depolymerization, in linking RhoA/ROCK pathway to dynamic alterations in actin cytoskeleton that are necessary for activation of NF-κB and thereby expression of ICAM-1 in these cells. Stimulation of human umbilical vein endothelial cells with thrombin resulted in Ser3 phosphorylation/inactivation of cofilin and formation of actin stress fibers in a ROCK-dependent manner. RNA interference knockdown of cofilin-1 stabilized the actin filaments and inhibited thrombin- and RhoA-induced NF-κB activity. Similarly, constitutively inactive mutant of cofilin-1 (Cof1-S3D), known to stabilize the actin cytoskeleton, inhibited NF-κB activity by thrombin. Overexpression of wild type cofilin-1 or constitutively active cofilin-1 mutant (Cof1-S3A), known to destabilize the actin cytoskeleton, also impaired thrombin-induced NF-κB activity. Additionally, depletion of cofilin-1 was associated with a marked reduction in ICAM-1 expression induced by thrombin. The effect of cofilin-1 depletion on NF-κB activity and ICAM-1 expression occurred downstream of IκBα degradation and was a result of impaired RelA/p65 nuclear translocation and consequently, RelA/p65 binding to DNA. Together, these data show that cofilin-1 occupies a central position in RhoA-actin pathway mediating nuclear translocation of RelA/p65 and expression of ICAM-1 in endothelial cells. PMID:19483084

Essential role of cofilin-1 in regulating thrombin-induced RelA/p65 nuclear translocation and intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells.

PubMed

Fazal, Fabeha; Bijli, Kaiser M; Minhajuddin, Mohd; Rein, Theo; Finkelstein, Jacob N; Rahman, Arshad

2009-07-31

Activation of RhoA/Rho-associated kinase (ROCK) pathway and the associated changes in actin cytoskeleton induced by thrombin are crucial for activation of NF-kappaB and expression of its target gene ICAM-1 in endothelial cells. However, the events acting downstream of RhoA/ROCK to mediate these responses remain unclear. Here, we show a central role of cofilin-1, an actin-binding protein that promotes actin depolymerization, in linking RhoA/ROCK pathway to dynamic alterations in actin cytoskeleton that are necessary for activation of NF-kappaB and thereby expression of ICAM-1 in these cells. Stimulation of human umbilical vein endothelial cells with thrombin resulted in Ser(3) phosphorylation/inactivation of cofilin and formation of actin stress fibers in a ROCK-dependent manner. RNA interference knockdown of cofilin-1 stabilized the actin filaments and inhibited thrombin- and RhoA-induced NF-kappaB activity. Similarly, constitutively inactive mutant of cofilin-1 (Cof1-S3D), known to stabilize the actin cytoskeleton, inhibited NF-kappaB activity by thrombin. Overexpression of wild type cofilin-1 or constitutively active cofilin-1 mutant (Cof1-S3A), known to destabilize the actin cytoskeleton, also impaired thrombin-induced NF-kappaB activity. Additionally, depletion of cofilin-1 was associated with a marked reduction in ICAM-1 expression induced by thrombin. The effect of cofilin-1 depletion on NF-kappaB activity and ICAM-1 expression occurred downstream of IkappaBalpha degradation and was a result of impaired RelA/p65 nuclear translocation and consequently, RelA/p65 binding to DNA. Together, these data show that cofilin-1 occupies a central position in RhoA-actin pathway mediating nuclear translocation of RelA/p65 and expression of ICAM-1 in endothelial cells.

Radiation and Heat Resistance of Moraxella-Acinetobacter in Meats

DTIC Science & Technology

1978-01-23

Parrish, and D. Duggan. 1956. Studies on a radiation-resistant Micrococcus . I. Isolation, morphology, cul- tural characteristics, and resistance to...Anderson, and P. R. Elliker. 1965. Ecology of Micrococcus radiodurans. Appl. Microbiol. 13: 1030. Lewis, N. F. 1973. Radio-resistant Micrococcus

Radiation tolerance of low resistivity, high voltage silicon solar cells

NASA Technical Reports Server (NTRS)

Weizer, V. G.; Weinberg, I.; Swartz, C. K.

1984-01-01

The radiation tolerance of the following three low resistivity, high voltage silicon solar cells was investigated: (1) the COMSAT MSD (multi-step diffused) cell, (2) the MinMIS cell, and (3) the MIND cell. A description of these solar cells is given along with drawings of their configurations. The diffusion length damage coefficients for the cells were calculated and presented. Solar cell spectral response was also discussed. Cells of the MinMIS type were judged to be unsuitable for use in the space radiation environment.

Determination of the radiation resistance order of high explosives by the two dimensional correlation X-ray photoelectron spectroscopy

NASA Astrophysics Data System (ADS)

Sui, Heliang; Hao, Xiaofei; Luo, Yiwei; Xu, Jinjiang; Zhong, Fachun; Xu, Ruijuan

2017-09-01

Two-dimensional X-ray photoelectron spectroscopy (2DXPS) was employed to obtain the radiation resistance order of high explosives. Mixed hexanitrohexaazaisowurtzitane (CL-20) and 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) were irradiated by X-ray radiation. The time-dependent N1s XPS spectra were collected. 2DXPS was used to analyze the variation of the binding energy peaks. The main degradation time of TATB was longer than that of CL-20. CL-20 changes occurred prior to that of TATB during radiation. These changes suggest that TATB exhibited higher radiation resistance property than CL-20. 2DXPS is a very useful method to distinguish the radiation resistance orders of materials.

Radiation Resistance of the U(Al, Si)3 Alloy: Ion-Induced Disordering

PubMed Central

Yaniv, Gili; Horak, Pavel; Vacik, Jiri; Mykytenko, Natalia; Rafailov, Gennady; Dahan, Itzchak; Fuks, David; Kiv, Arik

2018-01-01

During the exploitation of nuclear reactors, various U-Al based ternary intermetallides are formed in the fuel-cladding interaction layer. Structure and physical properties of these intermetallides determine the radiation resistance of cladding and, ultimately, the reliability and lifetime of the nuclear reactor. In current research, U(Al, Si)3 composition was studied as a potential constituent of an interaction layer. Phase content of the alloy of an interest was ordered U(Al, Si)3, structure of which was reported earlier, and pure Al (constituting less than 20 vol % of the alloy). This alloy was investigated prior and after the irradiation performed by Ar ions at 30 keV. The irradiation was performed on the transmission electron microscopy (TEM, JEOL, Japan) samples, characterized before and after the irradiation process. Irradiation induced disorder accompanied by stress relief. Furthermore, it was found that there is a dose threshold for disordering of the crystalline matter in the irradiated region. Irradiation at doses equal or higher than this threshold resulted in almost solely disordered phase. Using the program “Stopping and Range of Ions in Matter” (SRIM), the parameters of penetration of Ar ions into the irradiated samples were estimated. Based on these estimations, the dose threshold for ion-induced disordering of the studied material was assessed. PMID:29393870

Effect of Internet-Based Cognitive Apprenticeship Model (i-CAM) on Statistics Learning among Postgraduate Students.

PubMed

Saadati, Farzaneh; Ahmad Tarmizi, Rohani; Mohd Ayub, Ahmad Fauzi; Abu Bakar, Kamariah

2015-01-01

Because students' ability to use statistics, which is mathematical in nature, is one of the concerns of educators, embedding within an e-learning system the pedagogical characteristics of learning is 'value added' because it facilitates the conventional method of learning mathematics. Many researchers emphasize the effectiveness of cognitive apprenticeship in learning and problem solving in the workplace. In a cognitive apprenticeship learning model, skills are learned within a community of practitioners through observation of modelling and then practice plus coaching. This study utilized an internet-based Cognitive Apprenticeship Model (i-CAM) in three phases and evaluated its effectiveness for improving statistics problem-solving performance among postgraduate students. The results showed that, when compared to the conventional mathematics learning model, the i-CAM could significantly promote students' problem-solving performance at the end of each phase. In addition, the combination of the differences in students' test scores were considered to be statistically significant after controlling for the pre-test scores. The findings conveyed in this paper confirmed the considerable value of i-CAM in the improvement of statistics learning for non-specialized postgraduate students.

Comparative immunoexpression of ICAM-1, TGF-β1 and ki-67 in periapical and residual cysts.

PubMed

Martins, R; Armada, L; Dos Santos, T-C; Pires, F-R

2017-01-01

This study compared the immunohistochemical expression of ki-67, transforming growth factor beta 1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in inflammatory periapical cysts and residual cysts. The study sample was composed by 25 periapical cysts and 25 residual cysts and immunohistochemical reactions were carried out using antibodies directed against ICAM-1, TGF-β1 and ki-67. Clinical, radiological, gross, histological and immunohistochemical data were tabulated for descriptive and comparative analysis using the SPSS software and differences were considered statistically significant when p<0.05%. There were no differences between the expression of ICAM-1 (p=0.239) and TGF-β1 (p=0.258) when comparing both groups. Ki-67 labeling index was higher in residual cysts compared to periapical cysts (p=0.017). Results from the present study suggest that some specific inflammatory stimuli on residual cysts would modulate their mechanisms of etiopathogenesis, growing and repair.

[Circuit resistance training improved endothelial dysfunction in obese aged women].

PubMed

Rosety, Ignacio; Pery, María Teresa; Rosety, Jesús; García, Natalia; Rodríguez-Pareja, María Antonia; Brenes-Martín, Francisco; Díaz, Antonio; Rosety-Rodríguez, Manuel; Ordoñez, Francisco Javier; Rosety, Miguel Ángel

2016-02-16

It is widely accepted that obesity is associated with endothelial dysfunction. In a recent paper, we have also found circuit resistance training may reduce visceral fat in obese aged women. Accordingly, the current study was conducted to ascertain the effects of circuit resistance training on markers of endothelial dysfunction in this population group. In the present interventional study, a total of 48 obese aged women were recruited from the community. Twenty-four of them were randomly assigned to perform a 12-week resistance circuit training programme, 3-days per week. This training was circularly performed in 6 stations: arm curl, leg extension, seated row, leg curl, triceps extension and leg press. The Jamar handgrip electronic dynamometer was used to assess maximal handgrip strength of the dominant hand. Lastly, serum samples were analysed using an immunoassay (ELISA) for endothelin-1, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). When compared to baseline, resistance training significantly reduced serum levels of endothelin-1 (2.28 ± 0.7 vs. 1.98 ± 1.1 pg/ml; p = 0.019; d = 0.67) and ICAM-1 (290 ± 69 vs. 255 ± 76 ng/ml; p = 0.004; d = 0.92) in the experimental group. No significant changes in any of the tested outcomes were found in the control group. A short-term circuit resistance program improved endothelial dysfunction in aged obese women. Further studies on this topic are still required to consolidate this approach in clinical application.

Survival of antibiotic resistant bacteria following artificial solar radiation of secondary wastewater effluent.

PubMed

Glady-Croue, Julie; Niu, Xi-Zhi; Ramsay, Joshua P; Watkin, Elizabeth; Murphy, Riley J T; Croue, Jean-Philippe

2018-06-01

Urban wastewater treatment plant effluents represent one of the major emission sources of antibiotic-resistant bacteria (ARB) in natural aquatic environments. In this study, the effect of artificial solar radiation on total culturable heterotrophic bacteria and ARB (including amoxicillin-resistant, ciprofloxacin-resistant, rifampicin-resistant, sulfamethoxazole-resistant, and tetracycline-resistant bacteria) present in secondary effluent was investigated. Artificial solar radiation was effective in inactivating the majority of environmental bacteria, however, the proportion of strains with ciprofloxacin-resistance and rifampicin-resistance increased in the surviving populations. Isolates of Pseudomonas putida, Serratia marcescens, and Stenotrophomonas maltophilia nosocomial pathogens were identified as resistant to solar radiation and to at least three antibiotics. Draft genome sequencing and typing revealed isolates carrying multiple resistance genes; where S. maltophilia (resistant to all studied antibiotics) sequence type was similar to strains isolated in blood infections. Results from this study confirm that solar radiation reduces total bacterial load in secondary effluent, but may indirectly increase the relative abundance of ARB. Copyright © 2018 Elsevier B.V. All rights reserved.

Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule Are Induced by Ionizing Radiation on Lymphatic Endothelium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Ruiz, María E., E-mail: mrruiz@unav.es; Radiation Oncology, University Clinic, University of Navarra, Pamplona; Garasa, Saray

Purpose/Objectives: The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Materials/Methods: Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using amore » Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGFβ in this process anti-TGFβ blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGFβ and /or anti-ICAM1 blocking mAb. Results: We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGFβ. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Conclusion: Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to

Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule Are Induced by Ionizing Radiation on Lymphatic Endothelium.

PubMed

Rodriguez-Ruiz, María E; Garasa, Saray; Rodriguez, Inmaculada; Solorzano, Jose Luis; Barbes, Benigno; Yanguas, Alba; Teijeira, Alvaro; Etxeberria, Iñaki; Aristu, José Javier; Halin, Cornelia; Melero, Ignacio; Rouzaut, Ana

2017-02-01

The goal of this study was to assess the effects of ionizing radiation on the expression of the integrin ligands ICAM-1 and VCAM that control leucocyte transit by lymphatic endothelial cells. Confluent monolayers of primary human lymphatic endothelial cells (LEC) were irradiated with single dose of 2, 5, 10 or 20 Gy, with 6 MeV-x-rays using a Linear-Accelerator. ICAM-1 and VCAM expression was determined by flow cytometry. Human tissue specimens received a single dose of 20 Gy with 15 MeV-x-rays. MC38, B16-OVA or B16-VEGF-C tumors grown in C57BL/6 mice were irradiated with single dose of 20Gy using a Linear-Accelerator fitted with a 10mm Radiosurgery collimator. Clinical samples were obtained from patients previous and 4 weeks after complete standard radiotherapy. ICAM-1 and VCAM expression was detected in all tissue specimens by confocal microscopy. To understand the role of TGFβ in this process anti-TGFβ blocking mAb were injected i.p. 30min before radiotherapy. Cell adhesion to irradiated LEC was analyzed in adhesion experiments performed in the presence or in the absence of anti- TGFβ and /or anti-ICAM1 blocking mAb. We demonstrate that lymphatic endothelial cells in tumor samples experience induction of surface ICAM-1 and VCAM when exposed to ionizing radiation in a dose- and time-dependent manner. These effects can be recapitulated in cultured LEC, and are in part mediated by TGFβ. These data are consistent with increases in ICAM-1 and VCAM expression on LYVE-1+ endothelial cells in freshly explanted human tumor tissue and in mouse transplanted tumors after radiotherapy. Finally, ICAM-1 and VCAM expression accounts for enhanced adherence of human T lymphocytes to irradiated LEC. Our results show induction of ICAM-1 and VCAM on LVs in irradiated lesions and offer a starting point for elucidating the biological and therapeutic implications of targeting leukocyte traffic in combination to immunotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiation Effects of Commercial Resistive Random Access Memories

NASA Technical Reports Server (NTRS)

Chen, Dakai; LaBel, Kenneth A.; Berg, Melanie; Wilcox, Edward; Kim, Hak; Phan, Anthony; Figueiredo, Marco; Buchner, Stephen; Khachatrian, Ani; Roche, Nicolas

2014-01-01

We present results for the single-event effect response of commercial production-level resistive random access memories. We found that the resistive memory arrays are immune to heavy ion-induced upsets. However, the devices were susceptible to single-event functional interrupts, due to upsets from the control circuits. The intrinsic radiation tolerant nature of resistive memory makes the technology an attractive consideration for future space applications.

Lifitegrast: First LFA-1/ICAM-1 antagonist for treatment of dry eye disease.

PubMed

Paton, D M

2016-09-01

Dry eye disease is an extremely common condition affecting millions worldwide. The underlying pathophysiological mechanism is thought to be localized inflammation of the ocular surface resulting in the localization of T cells at this surface followed by their activation and subsequent liberation of cytokines. This effect on T cells results from the binding of lymphocyte function-associated antigen-1 (LFA-1) located on T cells to intercellular adhesion molecule 1 (ICAM-1) expressed on inflamed epithelium and endothelium, and on T cells. Lifitegrast is a T-cell integrin antagonist designed to mimic ICAM-1, thus blocking the interaction of LFA-1 and ICAM-1. Lifitegrast enters the systemic circulation to a limited extent thus reducing the likelihood of unwanted systemic reactions. Clinical trials in over 2,500 subjects with dry eye disease have shown that 5.0% lifitegrast given by ocular instillation causes a significant reduction in objective and subjective signs and symptoms of the disease. These beneficial effects are associated with a relatively low incidence of unwanted effects, almost all local in nature. In light of these findings, lifitegrast was approved by the Food and Drug Administration (FDA) in 2016 for the treatment of dry eye disease, the first drug with this mechanism of action to be so approved. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells.

PubMed

Lumsden, Amanda L; Ma, Yuefang; Ashander, Liam M; Stempel, Andrew J; Keating, Damien J; Smith, Justine R; Appukuttan, Binoy

2018-05-09

Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized. To address this issue, we undertook a comprehensive in silico analysis of the human ICR gene promoter region. We used genomic evolutionary rate profiling to identify a 115 base pair (bp) sequence within 500 bp upstream of the transcription start site of the annotated human ICR gene that was conserved across 25 eutherian genomes. A second constrained sequence upstream of the orthologous mouse gene (68 bp; conserved across 27 Eutherian genomes including human) was also discovered. Searching these elements identified 33 matrices predictive of binding sites for transcription factors known to be responsive to a broad range of pathological stimuli, including hypoxia, and metabolic and inflammatory proteins. Five phenotype-associated single nucleotide polymorphisms (SNPs) in the immediate vicinity of these elements included four SNPs (i.e. rs2569693, rs281439, rs281440 and rs11575074) predicted to impact binding motifs of transcription factors, and thus the expression of ICR and ICAM-1 genes, with potential to influence disease susceptibility. We verified that human retinal endothelial cells expressed ICR, and observed induction of expression by tumor necrosis factor-α.

ICAM-1 (CD54) expression on B lymphocytes is associated with their costimulatory function and can be increased by coactivation with IL-1 and IL-7.

PubMed

Dennig, D; Lacerda, J; Yan, Y; Gasparetto, C; O'Reilly, R J

1994-07-01

Recent studies have demonstrated that acute lymphoblastic leukemia-derived pre-B cell lines are deficient in their costimulatory function for T cell proliferation in response to the mitogen Con A and the superantigens TSST-1 and SEB. Stimulation of these pre-B cells with IL-7 increased their costimulatory function which involved the B7/CD28 pathway. In the present study, we stimulated T cells with Con A, TSST-1, and SEB in the presence of peripheral blood B lineage cells that do not constitutively express B7/BB1 on their surface and investigated whether their costimulatory function could also be enhanced by IL-7. We found that, in the presence of IL-1, stimulation with IL-7 increased the costimulatory function of B cells and their surface expression level of ICAM-1 (CD54). We then investigated whether costimulatory B cell function could be inhibited by blocking the ICAM-1/LFA-1 pathway. Addition of anti-ICAM-1 mAb to the coculture of T and B cells inhibited T cell proliferation by approximately 20%. In contrast, addition of anti-LFA-1 beta (CD18) mAb, directed against the T cell ligand of ICAM-1, inhibited T cell proliferation almost completely. To determine the role of ICAM-1 in costimulatory B cell function, we sorted B cells into ICAM-1low-and ICAM-1high-expressing populations. We found that B cells expressing high levels of surface ICAM-1 elicited significantly higher T cell responses than those with low levels, suggesting that the expression level of ICAM-1 on peripheral blood B cells correlates with their costimulatory function.

Ras Labs-CASIS-ISS NL experiment for synthetic muscle returned to Earth: resistance to ionizing radiation

NASA Astrophysics Data System (ADS)

Rasmussen, Lenore; Albers, Leila N.; Rodriguez, Simone; Gentile, Charles; Meixler, Lewis D.; Ascione, George; Hitchner, Robert; Taylor, James; Hoffman, Dan; Cylinder, David; Gaza, Ramona; Moy, Leon; Mark, Patrick S.; Prillaman, Daniel L.; Nodarse, Robert; Menegus, Michael J.; Ratto, Jo Ann; Thellen, Christopher T.; Froio, Danielle; Valenza, Logan; Poirier, Catherine; Sinkler, Charles; Corl, Dylan; Hablani, Surbhi; Fuerst, Tyler; Gallucci, Sergio; Blocher, Whitney; Liffland, Stephanie

2017-04-01

In anticipation of deep space travel, new materials are being explored to assist and relieve humans in dangerous environments, such as high radiation, extreme temperature, and extreme pressure. Ras Labs Synthetic Muscle™ - electroactive polymers (EAPs) that contract and expand at low voltages - which mimic the unique gentle-yet-strong nature of human tissue, is a potential asset to manned space travel through protective gear and human assist robotics and for unmanned space exploration through deep space. Gen 3 Synthetic Muscle™ was proven to be resistant to extreme temperatures, and there were indications that these materials would also be radiation resistant. The purpose of the Ras Labs-CASIS-ISS Experiment was to test the radiation resistivity of the third and fourth generation of these EAPs, as well as to make them even more radiation resistant. On Earth, exposure of the Generation 3 and Generation 4 EAPs to a Cs-137 radiation source for 47.8 hours with a total dose of 305.931 kRad of gamma radiation was performed at the US Department of Energy's Princeton Plasma Physics Laboratory (PPPL) at Princeton University, followed by pH, peroxide, Shore Hardness durometer, and electroactivity testing to determine the inherent radiation resistivity of these contractile EAPs, and to determine whether the EAPs could be made even more radiation resistant through the application of appropriate additives and coatings. The on Earth preliminary tests determined that selected Ras Labs EAPs were not only inherently radiation resistant, but with the appropriate coatings and additives, could be made even more radiation resistant. G-force testing to over 10 G's was performed at US Army's ARDEC Labs, with excellent results, in preparation for space flight to the International Space Station National Laboratory (ISS-NL). Selected samples of Generation 3 and Generation 4 Synthetic Muscle™, with various additives and coatings, were launched to the ISS-NL on April 14, 2015 on the

Effect of Internet-Based Cognitive Apprenticeship Model (i-CAM) on Statistics Learning among Postgraduate Students

PubMed Central

Saadati, Farzaneh; Ahmad Tarmizi, Rohani

2015-01-01

Because students’ ability to use statistics, which is mathematical in nature, is one of the concerns of educators, embedding within an e-learning system the pedagogical characteristics of learning is ‘value added’ because it facilitates the conventional method of learning mathematics. Many researchers emphasize the effectiveness of cognitive apprenticeship in learning and problem solving in the workplace. In a cognitive apprenticeship learning model, skills are learned within a community of practitioners through observation of modelling and then practice plus coaching. This study utilized an internet-based Cognitive Apprenticeship Model (i-CAM) in three phases and evaluated its effectiveness for improving statistics problem-solving performance among postgraduate students. The results showed that, when compared to the conventional mathematics learning model, the i-CAM could significantly promote students’ problem-solving performance at the end of each phase. In addition, the combination of the differences in students' test scores were considered to be statistically significant after controlling for the pre-test scores. The findings conveyed in this paper confirmed the considerable value of i-CAM in the improvement of statistics learning for non-specialized postgraduate students. PMID:26132553

Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts

PubMed Central

Kaneko, M; Inoue, H; Nakazawa, R; Azuma, N; Suzuki, M; Yamauchi, S; Margolin, S B; Tsubota, K; Saito, I

1998-01-01

Pirfenidone has been shown to modify some cytokine regulatory actions and inhibit fibroblast biochemical reactions resulting in inhibition of proliferation and collagen matrix synthesis by fibroblast. We have investigated the effect of pirfenidone on the expression of cell adhesion molecules. The synovial fibroblasts were treated with IL-1α in the presence or absence of pirfenidone (range 0–1000 μm), and assayed for the expression of adhesion molecules such as ICAM-1 and endothelial-leucocyte adhesion molecule-1 (E-selectin) by cell ELISA. Pirfenidone significantly down-regulated the expression of ICAM-1 on cultured synovial fibroblasts in a dose-dependent manner. In contrast, expression of E-selectin was not affected. Furthermore, we examined whether pirfenidone affects the cellular binding between cultured lymphocytes and IL-1α-stimulated synovial fibroblasts by in vitro binding assay and found their mutual binding was significantly suppressed in a dose-dependent manner by pirfenidone. It is speculated that down-regulation of ICAM-1 might be one of the novel mechanisms of action of pirfenidone. These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts. PMID:9697986

The dominant roles of ICAM-1-encoding gene in DNA vaccination against Japanese encephalitis virus are the activation of dendritic cells and enhancement of cellular immunity.

PubMed

Zhai, Yong-Zhen; Zhou, Yan; Ma, Li; Feng, Guo-He

2013-01-01

We investigated the cellular immune responses elicited by a plasmid DNA vaccine encoding prM-E protein from the Japanese encephalitis (JE) virus (JEV) with or without various forms of intercellular adhesion molecule (ICAM)-1 gene to maximize the immune responses evoked by the JE DNA vaccine. We observed that co-immunization with the construct containing murine ICAM-1 gene (pICAM-1) resulted in a significant increase in the percentage of CD4(+)T cells, high level of JEV-specific cytotoxic T lymphocyte response, and high production of T helper 1 (Th1)-type cytokines in splenic T cells. Furthermore, the co-expression of ICAM-1 and DNA immunogens was found to be more effective in generating T cell-mediated immune responses than those induced by immunization with pJME in combination with pICAM-1. Our results suggested that ICAM-1 enhanced T cell receptor signaling and activated Th1 immune responses in the JEV model system by increasing the induction of CD4(+)Th1 cell subset and activating dendritic cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Recent progress and tests of radiation resistant impregnation materials for Nb3Sn coils

NASA Astrophysics Data System (ADS)

Bossert, R.; Krave, S.; Ambrosio, G.; Andreev, N.; Chlachidze, G.; Nobrega, A.; Novitski, I.; Yu, M.; Zlobin, A. V.

2014-01-01

Fermilab is collaborating with Lawrence Berkeley National Laboratory (LBNL) and Brookhaven National Laboratory (BNL) (US-LARP collaboration) to develop a large-aperture Nb3Sn superconducting quadrupole for the Large Hadron Collider (LHC) luminosity upgrade. An important component of this work is the development of materials that are sufficiently radiation resistant for use in critical areas of the upgrade. This paper describes recent progress in characterization of materials, including the baseline CTD101K epoxy, cyanate ester blends, and Matrimid 5292, a bismaleimide-based system. Structural properties of "ten stacks" of cable impregnated with these materials are tested at room and cryogenic temperatures and compared to the baseline CT-101K. Experience with potting 1 and 2 meter long coils with Matrimid 5292 are described. Test results of a single 1-m coil impregnated with Matrimid 5292 are reported and compared to similar coils impregnated with the traditional epoxy.

Quercetin nanoparticle complex attenuated diabetic nephropathy via regulating the expression level of ICAM-1 on endothelium

PubMed Central

Tong, Fei; Liu, Suhuan; Yan, Bing; Li, Xuejun; Ruan, Shiwei; Yang, Shuyu

2017-01-01

The purpose of the study was to reveal the therapeutic effect of quercetin (QUE) nanoparticle complex on diabetic nephropathy (DN) by regulating the expression of intercellular adhesion molecular-1 (ICAM-1) on endothelium as compared to free QUE. QUE 10 mg/kg as a single abdominal subcutaneous injection daily for 8 weeks continuously in diabetic rats and 10 mg/kg QUE nanoparticle complex as a single abdominal subcutaneous injection every 5 days, continuously administered for 8 weeks to diabetic rats. Blood and left kidneys were collected; pathological change of kidney, renal function, oxidative stress level, blood glucose level, serum lipid, urine protein, and albumin/creatinine ratio were measured; and neutrophil adhesion, ICAM-1 expression, and CD11b+ cells infiltration were observed. Both QUE and QUE nanoparticle complex preconditioning ameliorated the pathological damage of kidney and improved renal function, alleviated renal oxidative stress injury, restricted inflammatory cells infiltration, and downregulated the ICAM-1 expression as compared to DN group, while QUE nanoparticle complex significantly alleviated this effect. PMID:29123394

Sustainably Sourced, Thermally Resistant, Radiation Hard Biopolymer

NASA Technical Reports Server (NTRS)

Pugel, Diane

2011-01-01

This material represents a breakthrough in the production, manufacturing, and application of thermal protection system (TPS) materials and radiation shielding, as this represents the first effort to develop a non-metallic, non-ceramic, biomaterial-based, sustainable TPS with the capability to also act as radiation shielding. Until now, the standing philosophy for radiation shielding involved carrying the shielding at liftoff or utilizing onboard water sources. This shielding material could be grown onboard and applied as needed prior to different radiation landscapes (commonly seen during missions involving gravitational assists). The material is a bioplastic material. Bioplastics are any combination of a biopolymer and a plasticizer. In this case, the biopolymer is a starch-based material and a commonly accessible plasticizer. Starch molecules are composed of two major polymers: amylase and amylopectin. The biopolymer phenolic compounds are common to the ablative thermal protection system family of materials. With similar constituents come similar chemical ablation processes, with the potential to have comparable, if not better, ablation characteristics. It can also be used as a flame-resistant barrier for commercial applications in buildings, homes, cars, and heater firewall material. The biopolymer is observed to undergo chemical transformations (oxidative and structural degradation) at radiation doses that are 1,000 times the maximum dose of an unmanned mission (10-25 Mrad), indicating that it would be a viable candidate for robust radiation shielding. As a comparison, the total integrated radiation dose for a three-year manned mission to Mars is 0.1 krad, far below the radiation limit at which starch molecules degrade. For electron radiation, the biopolymer starches show minimal deterioration when exposed to energies greater than 180 keV. This flame-resistant, thermal-insulating material is non-hazardous and may be sustainably sourced. It poses no hazardous

l-Theanine inhibits proinflammatory PKC/ERK/ICAM-1/IL-33 signaling, apoptosis, and autophagy formation in substance P-induced hyperactive bladder in rats.

PubMed

Tsai, Wen-Hsin; Wu, Chung-Hsin; Yu, Hong-Jeng; Chien, Chiang-Ting

2017-02-01

Upregulation of substance P (SP) and neurokinin-1 receptor (NK1R) activation induces pro-inflammatory bladder hyperactivity through the PKC/ERK/NF-κB/ICAM-1/IL-33 signaling pathways to increase the leukocyte infiltration and adhesion leading to reactive oxygen species (ROS) production, autophagy, and apoptosis. l-Theanine is a unique non-protein-forming amino acid present in tea (Camellia sinensis [L.] O. Kuntze) with its antioxidant, anti-inflammatory, and relaxation effects to improve cognition, mood, gastric ulcer injury, and cerebral ischemia/reperfusion injury, and posttraumatic stress disorder. We explored the protective effect of l-theanine on SP-induced bladder hyperactivity. In urethane-anesthetized female Wistar rats, we explored the transcystometrogram, pelvic nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, apoptosis-related Caspase 3/poly-(ADP-ribose)-polymerase (PARP), and autophagy-mediated LC3 II expression by Western blot, electrophoretic-mobility shift assay and immunohistochemistry, bladder ROS amount by a ultrasensitive chemiluminescence method, and possible ROS sources from the different leukocytes by specific stains in SP-evoked hyperactive bladder. l-Theanine dose-dependently depressed H 2 O 2 and HOCl activity in vitro. In urethane-anesthetized female Wistar rats, intra-arterial SP through NK1R activation increased voiding frequency (shortened intercontraction intervals) associated with the increase in bladder nerve activity, proinflammatory PKC/ERK/NF-κB/ICAM-1/IL-33 signaling, Caspase 3/PARP-mediated apoptosis, LC3 II-mediated autophagy, ROS amount, neutrophils adhesion, CD68 (monocyte/macrophage) infiltration, and mast cells degranulation in the hyperactive bladder. Intragastrical l-theanine (15 mg/kg) twice daily for 2 weeks efficiently ameliorated all the enhanced parameters in the SP-treated hyperactive bladder. In conclusion, l-theanine through antioxidant and anti-inflammatory actions ameliorates SP

Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moulder, J.E.; Hopwood, L.E.; Volk, D.M.

1991-02-01

The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiationmore » doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors.« less

[Influence of Kudou Shencha decotion on INF-gamma, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats].

PubMed

Xia, Li-Ying; Liu, Wei-Jia; Li, Ming-Xi; Ge, Wen-Jin; Gao, Xue-Min; Zhang, Jian-Jun

2014-05-01

To investigate the influence of Kudou Shencha decotion on INF-y, ICAM-1, MCP-1 levels of prostate tissue homogenate in immunity prostatitis model rats. Forty Wistar male rats were divided into 5 groups randomly: Kudou Shencha decotion group with high dosage and low dosage, Qianleitai group, the model control group and normal group. The rat model of chronic nonbacterial prostatitis was established by multiple hypodermical injection of the suspension of prostatic protein purification with Freund's completed adjuvant. The level of intercellular adhesion molecule (ICAM-1), interferon gamma (INF-gamma) and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme linked immunosorbent assay (ELISA). The content of ICAM-1 and MCP-1 in the model group was higher than that of the normal group (P < 0.05), the content of ICAM-1 was obviously decreased in Kudou Shencha decotion group with high dosage (P <0.05), the contents of MCP-1 were all obviously decreased in Kudou Shencha decotion groups and Qianlietai group. Compared with the model group, the contents of INF-gamma in all treatment groups were decreased insignificantly. Kudou Shencha decotion has the action of lowering the level of ICAM-1 and MCP-1, which may be one of the mechanisms of Kudou Shencha decotion in the therapy of chronic prostatitis.

Th17 Cells Induce Dopaminergic Neuronal Death via LFA-1/ICAM-1 Interaction in a Mouse Model of Parkinson's Disease.

PubMed

Liu, Zhan; Huang, Yan; Cao, Bei-Bei; Qiu, Yi-Hua; Peng, Yu-Ping

2017-12-01

T helper (Th)17 cells, a subset of CD4 + T lymphocytes, have strong pro-inflammatory property and appear to be essential in the pathogenesis of many inflammatory diseases. However, the involvement of Th17 cells in Parkinson's disease (PD) that is characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the nigrostriatal system is unclear. Here, we aimed to demonstrate that Th17 cells infiltrate into the brain parenchyma and induce neuroinflammation and DAergic neuronal death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 1-methyl-4-phenylpyridinium (MPP + )-induced PD models. Blood-brain barrier (BBB) disruption in the substantia nigra (SN) was assessed by the signal of FITC-labeled albumin that was injected into blood circulation via the ascending aorta. Live cell imaging system was used to observe a direct contact of Th17 cells with neurons by staining these cells using the two adhesion molecules, leukocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1, respectively. Th17 cells invaded into the SN where BBB was disrupted in MPTP-induced PD mice. Th17 cells exacerbated DAergic neuronal loss and pro-inflammatory/neurotrophic factor disorders in MPP + -treated ventral mesencephalic (VM) cell cultures. A direct contact of LFA-1-stained Th17 cells with ICAM-1-stained VM neurons was dynamically captured. Either blocking LFA-1 in Th17 cells or blocking ICAM-1 in VM neurons with neutralizing antibodies abolished Th17-induced DAergic neuronal death. These results establish that Th17 cells infiltrate into the brain parenchyma of PD mice through lesioned BBB and exert neurotoxic property by promoting glial activation and importantly by a direct damage to neurons depending on LFA-1/ICAM-1 interaction.

Induced DNA demethylation by targeting Ten-Eleven Translocation 2 to the human ICAM-1 promoter

PubMed Central

Chen, Hui; Kazemier, Hinke G; de Groote, Marloes L.; Ruiters, Marcel H. J.; Xu, Guo-Liang; Rots, Marianne G.

2014-01-01

Increasing evidence indicates that active DNA demethylation is involved in several processes in mammals, resulting in developmental stage-specificity and cell lineage-specificity. The recently discovered Ten-Eleven Translocation (TET) dioxygenases are accepted to be involved in DNA demethylation by initiating 5-mC oxidation. Aberrant DNA methylation profiles are associated with many diseases. For example in cancer, hypermethylation results in silencing of tumor suppressor genes. Such silenced genes can be re-expressed by epigenetic drugs, but this approach has genome-wide effects. In this study, fusions of designer DNA binding domains to TET dioxygenase family members (TET1, -2 or -3) were engineered to target epigenetically silenced genes (ICAM-1, EpCAM). The effects on targeted CpGs’ methylation and on expression levels of the target genes were assessed. The results indicated demethylation of targeted CpG sites in both promoters for targeted TET2 and to a lesser extent for TET1, but not for TET3. Interestingly, we observed re-activation of transcription of ICAM-1. Thus, our work suggests that we provided a mechanism to induce targeted DNA demethylation, which facilitates re-activation of expression of the target genes. Furthermore, this Epigenetic Editing approach is a powerful tool to investigate functions of epigenetic writers and erasers and to elucidate consequences of epigenetic marks. PMID:24194590

Erythrocyte plasma membrane-bound ERK1/2 activation promotes ICAM-4-mediated sickle red cell adhesion to endothelium.

PubMed

Zennadi, Rahima; Whalen, Erin J; Soderblom, Erik J; Alexander, Susan C; Thompson, J Will; Dubois, Laura G; Moseley, M Arthur; Telen, Marilyn J

2012-02-02

The core pathology of sickle cell disease (SCD) starts with the erythrocyte (RBC). Aberration in MAPK/ERK1/2 signaling, which can regulate cell adhesion, occurs in diverse pathologies. Because RBCs contain abundant ERK1/2, we predicted that ERK1/2 is functional in sickle (SS) RBCs and promotes adherence, a hallmark of SCD. ERK1/2 remained active in SS but not normal RBCs. β(2)-adrenergic receptor stimulation by epinephrine can enhance ERK1/2 activity only in SS RBCs via PKA- and tyrosine kinase p72(syk)-dependent pathways. ERK signaling is implicated in RBC ICAM-4 phosphorylation, promoting SS RBC adhesion to the endothelium. SS RBC adhesion and phosphorylation of both ERK and ICAM-4 all decreased with continued cell exposure to epinephrine, implying that activation of ICAM-4-mediated SS RBC adhesion is temporally associated with ERK1/2 activation. Furthermore, recombinant ERK2 phosphorylated α- and β-adducins and dematin at the ERK consensus motif. Cytoskeletal protein 4.1 also showed dynamic phosphorylation but not at the ERK consensus motif. These results demonstrate that ERK activation induces phosphorylation of cytoskeletal proteins and the adhesion molecule ICAM-4, promoting SS RBC adhesion to the endothelium. Thus, blocking RBC ERK1/2 activation, such as that promoted by catecholamine stress hormones, could ameliorate SCD pathophysiology.

Microbial cells can cooperate to resist high-level chronic ionizing radiation

PubMed Central

Gaidamakova, Elena K.; Tkavc, Rok; Grichenko, Olga; Klimenkova, Polina; Volpe, Robert P.; Daly, Michael J.

2017-01-01

Understanding chronic ionizing radiation (CIR) effects is of utmost importance to protecting human health and the environment. Diverse bacteria and fungi inhabiting extremely radioactive waste and disaster sites (e.g. Hanford, Chernobyl, Fukushima) represent new targets of CIR research. We show that many microorganisms can grow under intense gamma-CIR dose rates of 13–126 Gy/h, with fungi identified as a particularly CIR-resistant group of eukaryotes: among 145 phylogenetically diverse strains tested, 78 grew under 36 Gy/h. Importantly, we demonstrate that CIR resistance can depend on cell concentration and that certain resistant microbial cells protect their neighbors (not only conspecifics, but even radiosensitive species from a different phylum), from high-level CIR. We apply a mechanistically-motivated mathematical model of CIR effects, based on accumulation/removal kinetics of reactive oxygen species (ROS) and antioxidants, in bacteria (3 Escherichia coli strains and Deinococcus radiodurans) and in fungi (Candida parapsilosis, Kazachstania exigua, Pichia kudriavzevii, Rhodotorula lysinophila, Saccharomyces cerevisiae, and Trichosporon mucoides). We also show that correlations between responses to CIR and acute ionizing radiation (AIR) among studied microorganisms are weak. For example, in D. radiodurans, the best molecular correlate for CIR resistance is the antioxidant enzyme catalase, which is dispensable for AIR resistance; and numerous CIR-resistant fungi are not AIR-resistant. Our experimental findings and quantitative modeling thus demonstrate the importance of investigating CIR responses directly, rather than extrapolating from AIR. Protection of radiosensitive cell-types by radioresistant ones under high-level CIR is a potentially important new tool for bioremediation of radioactive sites and development of CIR-resistant microbiota as radioprotectors. PMID:29261697

Microbial cells can cooperate to resist high-level chronic ionizing radiation.

PubMed

Shuryak, Igor; Matrosova, Vera Y; Gaidamakova, Elena K; Tkavc, Rok; Grichenko, Olga; Klimenkova, Polina; Volpe, Robert P; Daly, Michael J

2017-01-01

Understanding chronic ionizing radiation (CIR) effects is of utmost importance to protecting human health and the environment. Diverse bacteria and fungi inhabiting extremely radioactive waste and disaster sites (e.g. Hanford, Chernobyl, Fukushima) represent new targets of CIR research. We show that many microorganisms can grow under intense gamma-CIR dose rates of 13-126 Gy/h, with fungi identified as a particularly CIR-resistant group of eukaryotes: among 145 phylogenetically diverse strains tested, 78 grew under 36 Gy/h. Importantly, we demonstrate that CIR resistance can depend on cell concentration and that certain resistant microbial cells protect their neighbors (not only conspecifics, but even radiosensitive species from a different phylum), from high-level CIR. We apply a mechanistically-motivated mathematical model of CIR effects, based on accumulation/removal kinetics of reactive oxygen species (ROS) and antioxidants, in bacteria (3 Escherichia coli strains and Deinococcus radiodurans) and in fungi (Candida parapsilosis, Kazachstania exigua, Pichia kudriavzevii, Rhodotorula lysinophila, Saccharomyces cerevisiae, and Trichosporon mucoides). We also show that correlations between responses to CIR and acute ionizing radiation (AIR) among studied microorganisms are weak. For example, in D. radiodurans, the best molecular correlate for CIR resistance is the antioxidant enzyme catalase, which is dispensable for AIR resistance; and numerous CIR-resistant fungi are not AIR-resistant. Our experimental findings and quantitative modeling thus demonstrate the importance of investigating CIR responses directly, rather than extrapolating from AIR. Protection of radiosensitive cell-types by radioresistant ones under high-level CIR is a potentially important new tool for bioremediation of radioactive sites and development of CIR-resistant microbiota as radioprotectors.

Phosphatidyl inositol-3 kinase (PIK3CA) E545K mutation confers cisplatin resistance and a migratory phenotype in cervical cancer cells.

PubMed

Arjumand, Wani; Merry, Cole D; Wang, Chen; Saba, Elias; McIntyre, John B; Fang, Shujuan; Kornaga, Elizabeth; Ghatage, Prafull; Doll, Corinne M; Lees-Miller, Susan P

2016-12-13

The phosphatidylinositol-3 kinase (PI3K)/Akt/mTOR signaling pathway is activated in many human cancers. Previously, we reported that patients with early stage cervical cancer whose tumours harbour PIK3CA exon 9 or 20 mutations have worse overall survival in response to treatment with radiation and cisplatin than patients with wild-type PIK3CA. The purpose of this study was to determine whether PIK3CA-E545K mutation renders cervical cancer cells more resistant to cisplatin and/or radiation, and whether PI3K inhibition reverses the phenotype. We found that CaSki cells that are heterozygous for the PIK3CA-E545K mutation are more resistant to cisplatin or cisplatin plus radiation than either HeLa or SiHa cells that express only wild-type PIK3CA. Similarly, HeLa cells engineered to stably express PIK3CA-E545K were more resistant to cisplatin or cisplatin plus radiation than cells expressing only wild-type PIK3CA or with PIK3CA depleted. Cells expressing the PIK3CA-E545K mutation also had constitutive PI3K pathway activation and increased cellular migration and each of these phenotypes was reversed by treatment with the PI3K inhibitor GDC-0941/Pictilisib. Our results suggests that cervical cancer patients whose tumours are positive for the PIK3CA-E545K mutation may benefit from PI3K inhibitor therapy in concert with standard cisplatin and radiation therapy.

Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy

PubMed Central

Kim, Byeong Mo; Hong, Yunkyung; Lee, Seunghoon; Liu, Pengda; Lim, Ji Hong; Lee, Yong Heon; Lee, Tae Ho; Chang, Kyu Tae; Hong, Yonggeun

2015-01-01

Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death. We also discuss cytogenetic variations representative of IR-induced DNA damage and genomic instability. Most importantly, we focus on several pathways and their associated marker proteins responsible for cancer resistance and its therapeutic implications in terms of cancer cell death of various types and characteristics. Finally, we propose radiation-sensitization strategies, such as the modification of fractionation, inflammation, and hypoxia and the combined treatment, that can counteract the resistance of tumors to IR. PMID:26569225

Immunologic changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in pediatric patients treated for psoriasis with the Goeckerman regimen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borska, L.; Fiala, Z.; Krejsek, J.

2007-11-15

Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1, sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha and sICAM-1more » decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL-8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL-8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.« less

Analysis of DNA methylation and gene expression in radiation-resistant head and neck tumors.

PubMed

Chen, Xiaofei; Liu, Liang; Mims, Jade; Punska, Elizabeth C; Williams, Kristin E; Zhao, Weiling; Arcaro, Kathleen F; Tsang, Allen W; Zhou, Xiaobo; Furdui, Cristina M

2015-01-01

Resistance to radiation therapy constitutes a significant challenge in the treatment of head and neck squamous cell cancer (HNSCC). Alteration in DNA methylation is thought to play a role in this resistance. Here, we analyzed DNA methylation changes in a matched model of radiation resistance for HNSCC using the Illumina HumanMethylation450 BeadChip. Our results show that compared to radiation-sensitive cells (SCC-61), radiation-resistant cells (rSCC-61) had a significant increase in DNA methylation. After combining these results with microarray gene expression data, we identified 84 differentially methylated and expressed genes between these 2 cell lines. Ingenuity Pathway Analysis revealed ILK signaling, glucocorticoid receptor signaling, fatty acid α-oxidation, and cell cycle regulation as top canonical pathways associated with radiation resistance. Validation studies focused on CCND2, a protein involved in cell cycle regulation, which was identified as hypermethylated in the promoter region and downregulated in rSCC-61 relative to SCC-61 cells. Treatment of rSCC-61 and SCC-61 with the DNA hypomethylating agent 5-aza-2'deoxycitidine increased CCND2 levels only in rSCC-61 cells, while treatment with the control reagent cytosine arabinoside did not influence the expression of this gene. Further analysis of HNSCC data from The Cancer Genome Atlas found increased methylation in radiation-resistant tumors, consistent with the cell culture data. Our findings point to global DNA methylation status as a biomarker of radiation resistance in HNSCC, and suggest a need for targeted manipulation of DNA methylation to increase radiation response in HNSCC.

Infection of human intestinal epithelial cells with invasive bacteria upregulates apical intercellular adhesion molecule-1 (ICAM)-1) expression and neutrophil adhesion.

PubMed Central

Huang, G T; Eckmann, L; Savidge, T C; Kagnoff, M F

1996-01-01

The acute host response to gastrointestinal infection with invasive bacteria is characterized by an accumulation of neutrophils in the lamina propria, and neutrophil transmigration to the luminal side of the crypts. Intestinal epithelial cells play an important role in the recruitment of inflammatory cells to the site of infection through the secretion of chemokines. However, little is known regarding the expression, by epithelial cells, of molecules that are involved in interactions between the epithelium and neutrophils following bacterial invasion. We report herein that expression of ICAM-1 on human colon epithelial cell lines, and on human enterocytes in an in vivo model system, is upregulated following infection with invasive bacteria. Increased ICAM-1 expression in the early period (4-9 h) after infection appeared to result mainly from a direct interaction between invaded bacteria and host epithelial cells since it co-localized to cells invaded by bacteria, and the release of soluble factors by epithelial cells played only a minor role in mediating increased ICAM-1 expression. Furthermore, ICAM-1 was expressed on the apical side of polarized intestinal epithelial cells, and increased expression was accompanied by increased neutrophil adhesion to these cells. ICAM-1 expression by intestinal epithelial cells following infection with invasive bacteria may function to maintain neutrophils that have transmigrated through the epithelium in close contact with the intestinal epithelium, thereby reducing further invasion of the mucosa by invading pathogens. PMID:8755670

Radiation induction of drug resistance in RIF-1 tumors and tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopwood, L.E.; Moulder, J.E.

1989-11-01

The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not formore » ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance.« less

Spilanthol Inhibits COX-2 and ICAM-1 Expression via Suppression of NF-κB and MAPK Signaling in Interleukin-1β-Stimulated Human Lung Epithelial Cells.

PubMed

Huang, Wen-Chung; Wu, Ling-Yu; Hu, Sindy; Wu, Shu-Ju

2018-06-30

Spilanthol a phytochemical derived from the Spilanthes acmella plant has antimicrobial, antioxidant, and anti-inflammatory properties. This study evaluated its effects on the expression of intercellular adhesion molecule 1 (ICAM-1) and inflammation-related mediators in IL-1β-stimulated human lung epithelial A549 cells. Human lung epithelial A549 cells were pretreated with various concentrations of spilanthol (3-100 μM) followed by treatment with IL-1β to induce inflammation. The protein levels of pro-inflammatory cytokines, chemokines, and prostaglandin E2 (PGE2) were measured using ELISA. Cyclooxygenase-2 (COX-2), heme oxygenase (HO-1), nuclear transcription factor kappa-B (NF-κB), and mitogen-activated protein kinase (MAPK) were measured by immunoblotting. The mRNA expression levels of ICAM-1 and MUC5AC were determined by real-time polymerase chain reaction. Spilanthol decreased the expression of PGE 2 , COX-2, TNF-α, and MCP-1. It also decreased ICAM-1 expression and suppressed monocyte adhesion to IL-1β-stimulated A549 cells. Spilanthol also significantly inhibited the phosphorylation of MAPK and I-κB. These results suggest that spilanthol exerts anti-inflammatory effects by inhibiting the expression of the pro-inflammatory cytokines, COX-2, and ICAM-1 by inhibiting the NF-κB and MAPK signaling pathways. Graphical Abstract ᅟ.

Lnk adaptor suppresses radiation resistance and radiation-induced B-cell malignancies by inhibiting IL-11 signaling

PubMed Central

Louria-Hayon, Igal; Frelin, Catherine; Ruston, Julie; Gish, Gerald; Jin, Jing; Kofler, Michael M.; Lambert, Jean-Philippe; Adissu, Hibret A.; Milyavsky, Michael; Herrington, Robert; Minden, Mark D.; Dick, John E.; Gingras, Anne-Claude; Iscove, Norman N.; Pawson, Tony

2013-01-01

The Lnk (Sh2b3) adaptor protein dampens the response of hematopoietic stem cells and progenitors (HSPCs) to a variety of cytokines by inhibiting JAK2 signaling. As a consequence, Lnk−/− mice develop hematopoietic hyperplasia, which progresses to a phenotype resembling the nonacute phase of myeloproliferative neoplasm. In addition, Lnk mutations have been identified in human myeloproliferative neoplasms and acute leukemia. We find that Lnk suppresses the development of radiation-induced acute B-cell malignancies in mice. Lnk-deficient HSPCs recover more effectively from irradiation than their wild-type counterparts, and this resistance of Lnk−/− HSPCs to radiation underlies the subsequent emergence of leukemia. A search for the mechanism responsible for radiation resistance identified the cytokine IL-11 as being critical for the ability of Lnk−/− HSPCs to recover from irradiation and subsequently become leukemic. In IL-11 signaling, wild-type Lnk suppresses tyrosine phosphorylation of the Src homology region 2 domain-containing phosphatase-2/protein tyrosine phosphatase nonreceptor type 11 and its association with the growth factor receptor-bound protein 2, as well as activation of the Erk MAP kinase pathway. Indeed, Src homology region 2 domain-containing phosphatase-2 has a binding motif for the Lnk Src Homology 2 domain that is phosphorylated in response to IL-11 stimulation. IL-11 therefore drives a pathway that enhances HSPC radioresistance and radiation-induced B-cell malignancies, but is normally attenuated by the inhibitory adaptor Lnk. PMID:24297922

Association of ICAM-1 and HMGA1 Gene Variants with Retinopathy in Type 2 Diabetes Mellitus Among Chinese Individuals.

PubMed

Lv, Zhiping; Li, Ying; Wu, Yongzhong; Qu, Yi

2016-08-01

To evaluate the association of intercellular cell-adhesion molecule 1 (ICAM-1) and high-mobility group A1 (HMGA1) gene variants with diabetic retinopathy (DR) in a Chinese type 2 diabetes mellitus (T2DM) cohort. A total of 792 patients with T2DM were enrolled and categorized into two groups: (1) the DR group consisted of 448 patients, which was further subclassified into the proliferative DR (PDR) group with 220 patients and the nonproliferative DR (NPDR) group with 228 patients; (2) the diabetes without retinopathy (DNR) group comprised 344 patients who had no signs of DR. The single-nucleotide polymorphism (SNP) rs5498 in ICAM-1 gene and IVS5-13insC variant in HMGA1 gene were genotyped. No evident association was found in the allele frequencies between SNP rs5498 in ICAM-1 gene and DR patients; the combined p values for the additive, dominant, and recessive models in genotype were greater than 0.05. No significant association was identified between the IVS5-13insC variant in HMGA1 gene and DR individuals. Our results revealed that SNP rs5498 in ICAM-1 gene and IVS5-13insC variant in HMGA1 gene were not associated with the susceptibility of DR in the Chinese T2DM cohort.

Reprogramming mediated radio-resistance of 3D-grown cancer cells.

PubMed

Xue, Gang; Ren, Zhenxin; Grabham, Peter W; Chen, Yaxiong; Zhu, Jiayun; Du, Yarong; Pan, Dong; Li, Xiaoman; Hu, Burong

2015-07-01

In vitro 3D growth of tumors is a new cell culture model that more closely mimics the features of the in vivo environment and is being used increasingly in the field of biological and medical research. It has been demonstrated that cancer cells cultured in 3D matrices are more radio-resistant compared with cells in monolayers. However, the mechanisms causing this difference remain unclear. Here we show that cancer cells cultured in a 3D microenvironment demonstrated an increase in cells with stem cell properties. This was confirmed by the finding that cells in 3D cultures upregulated the gene and protein expression of the stem cell reprogramming factors such as OCT4, SOX2, NANOG, LIN28 and miR-302a, compared with cells in monolayers. Moreover, the expression of β-catenin, a regulating molecule of reprogramming factors, also increased in 3D-grown cancer cells. These findings suggest that cancer cells were reprogrammed to become stem cell-like cancer cells in a 3D growth culture microenvironment. Since cancer stem cell-like cells demonstrate an increased radio-resistance and chemo-resistance, our results offer a new perspective as to why. Our findings shed new light on understanding the features of the 3D growth cell model and its application in basic research into clinical radiotherapy and medicine. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

SU-G-TeP3-09: Proton Minibeam Radiation Therapy Increases Normal Tissue Resistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prezado, Y; Gonzalez-Infantes, W; Juchaux, M

Purpose: The dose tolerances of normal tissues continue being the main limitation in radiotherapy. To overcome it, we recently proposed a novel concept: proton minibeam radiation therapy (pMBRT) [1]. It allies the physical advantages of protons with the normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams (minibeam radiation therapy) [2]. The dose distributions are such that the tumor receives a homogeneous dose distribution, while normal tissues benefit from the spatial fractionation of the dose. The objective of our work was to implement this promising technique at a clinical center (Proton therapy center in Orsay) in order tomore » evaluate the potential gain in tissue sparing. Methods: Dose distributions were measured by means of gafchromic films and a PTW microdiamond detector (60019). Once the dosimetry was established, the whole brain of 7 weeks old male Fischer 344 rats was irradiated. Half of the animals received conventional seamless proton irradiation (25 Gy in one fraction). The other rats were irradiated with pMBRT (58 Gy peak dose in one fraction). The average dose deposited in the same targeted volume was in both cases 25 Gy. Results: The first complete set of dosimetric data in such small proton field sizes was obtained [3]. Rats treated with conventional proton irradiation exhibited severe moist desquamation and permanent epilation afterwards. The minibeam group, on the other hand, exhibited no skin damage and no clinical symptoms. MRI imaging and histological analysis are planned at 6 months after irradiation. Conclusion: Our preliminary results indicate that pMBRT leads to an increase in tissue resistance. This can open the door to an efficient treatment of very radioresistant tumours. [1] Prezado et al. Med. Phys. 40, 031712, 1–8 (2013).[2] Prezado et al., Rad. Research. 184, 314-21 (2015). [3] Peucelle et al., Med. Phys. 42 7108-13 (2015).« less

Effect of selected solutes on growth and recovery of a radiation-resistant Moraxella

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruns, M.A.; Maxcy, R.B.

1978-01-01

A highly radiation-resistant Moraxella sp. from beef was more resistant to gamma radiation in frozen beef than Clostridium botulinum 33A spores. Even though the Moraxella sp. was extremely radiation-resistant, its recovery after irradiation was markedly influenced by the plating medium. Fewer colony-forming units were recovered in Tryptic Soy Agar (TSA) than in Plate Count Agar (PCA), and differences in recovery became more pronounced with increasing radiation dose. Growth studies of the nonirradiated Moraxella sp. suggested the presence of dialyzable inhibitory factor(s) in Trypticase Soy Broth (TSB) and TSA. The low (0.5 percent) concentration of NaCl in TSA was shown tomore » be mainly responsible for the slow growth and reduced recovery after irradiation. Reduced recovery was also obtained by plating the Moraxella sp. in PCA plus 0.5 percent NaCl or PCA plus 6 percent glucose after irradiation. It was noted that 2 other highly radiation-resistant isolates identified as Moraxella sp. gave similar results. Sensitivity to low solute concentrations, therefore, appeared to be a general phenomenon for this group.« less

Enhanced resistance of the Pamirs high-mountain strain of Cryptococcus albidus to UV radiation of an ecological range

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strakhovskaya, M.G.; Lavrukhina, O.G.; Fraikin, G.Y.

The results of a comparative analysis of the resistance of Pamirs high-mountain and lowland strains of the yeast Cryptococcus albidus to UV radiation of an ecological range are presented. A high-mountain strain, adapted to elevated UV radiation in its habitat, was found to be more resistant to UV light of a total ecorange (290-400 nm), including medium-wave (290-320 nm) and long-wave (320-400 nm) UV ranges. The enhanced UV light resistance of the high-mountain strain can be explained by efficient functioning of the excision DNA repair system. 7 refs., 3 tabs.

Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells.

PubMed

Huang, Wen-Chung; Wu, Shu-Ju; Tu, Rong-Syuan; Lai, You-Rong; Liou, Chian-Jiun

2015-06-01

Phloretin, a flavonoid isolated from the apple tree, is reported to have anti-inflammatory, anti-oxidant, and anti-adiposity effects. In this study, we evaluated the suppressive effects of phloretin on intercellular adhesion molecule 1 (ICAM-1) and cyclooxygenase (COX)-2 expression in IL-1β-stimulated human lung epithelial A549 cells. The cells were pretreated with various concentrations of phloretin (3-100 μM), followed by induced inflammation by IL-1β. Phloretin inhibited levels of prostaglandin E2, decreased COX-2 expression, and suppressed IL-8, monocyte chemotactic protein 1, and IL-6 production. It also decreased ICAM-1 gene and protein expression and suppressed monocyte adhesion to inflammatory A549 cells. Phloretin also significantly inhibited Akt and mitogen-activated protein kinase (MAPK) phosphorylation and decreased nuclear transcription factor kappa-B (NF-κB) subunit p65 protein translocation into the nucleus. In addition, ICAM-1 and COX-2 expression was suppressed by pretreatment with both MAPK inhibitors and phloretin in inflammatory A549 cells. However, phlorizin, a derivative of phloretin, did not suppress the inflammatory response in IL-1β-stimulated A549 cells. These results suggest that phloretin might have an anti-inflammatory effect by inhibiting proinflammatory cytokine, COX-2, and ICAM-1 expression via blocked NF-κB and MAPK signaling pathways.

Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makarova, Kira S.; Omelchenko, Marina V.; Gaidamakova, Elena K.

Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at itsoptimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radioduransmore » genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to

Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans.

PubMed

Jung, Kwang-Woo; Yang, Dong-Hoon; Kim, Min-Kyu; Seo, Ho Seong; Lim, Sangyong; Bahn, Yong-Sun

2016-11-29

The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans IMPORTANCE: Although there are no natural environments under intense radiation, some living organisms

High Radiation Resistance IMM Solar Cell

NASA Technical Reports Server (NTRS)

Pan, Noren

2015-01-01

Due to high launch costs, weight reduction is a key driver for the development of new solar cell technologies suitable for space applications. This project is developing a unique triple-junction inverted metamorphic multijunction (IMM) technology that enables the manufacture of very lightweight, low-cost InGaAsP-based multijunction solar cells. This IMM technology consists of indium (In) and phosphorous (P) solar cell active materials, which are designed to improve the radiation-resistant properties of the triple-junction solar cell while maintaining high efficiency. The intrinsic radiation hardness of InP materials makes them of great interest for building solar cells suitable for deployment in harsh radiation environments, such as medium Earth orbit and missions to the outer planets. NASA Glenn's recently developed epitaxial lift-off (ELO) process also will be applied to this new structure, which will enable the fabrication of the IMM structure without the substrate.

PREFACE: International Conference on the Applications of the Mössbauer Effect (ICAME 2009)

NASA Astrophysics Data System (ADS)

Müller, Herbert; Reissner, Michael; Steiner, Walter; Wiesinger, Günter

2010-04-01

The International Conference on the Applications of the Mössbauer Effect (ICAME2009) was held for the first time in Austria, at the Vienna University of Technology on 19-24 July 2009. This largest conference of the Mössbauer community attracted much interest, nearly 500 colleagues announced their intention to participate. Unfortunately, due to the world-wide finance crisis, in the end many could not manage to come. Nevertheless 380 abstracts were submitted. More than 300 participants from 38 countries were present at the conference. The programme contained 20 invited talks, selected by the international advisory board. 49 contributions were selected for oral presentation. Following the advice of the IBAME board, no parallel sessions were organized. Therefore most of the work was presented as posters, attached for the whole week, giving thus the opportunity for intense discussions outside of the poster sessions. A special tutorial session, dedicated to Mössbauer spectroscopy with synchrotron radiation, organized by R Rüffer was held on the first day. It was included in the conference programme giving all participants the opportunity to attend this meeting. Although lasting until late in the evening, the audience was always well occupied. New developments in the field of iron-containing superconductors were discussed in a micro symposium. The scientific level of the whole conference was high. After thorough peer-reviewing, 147 papers were accepted by the referees and are presented in this volume. ICAME2009 was possible due to the efforts of many people, in the organizing committee, the programme committee and the editorial board and to the students who took care of the participants during the conference and all social activities. ICAME2009 was in several ways a special conference. It was the 30th in the series of ICAME meetings, and the first after the celebration of 50 years of the Mössbauer Effect. In 2009 Rudolf Mössbauer also celebrated his 80th birthday

Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

PubMed

Ortiz Segura, Maria Del Carmen; Del Río Navarro, Blanca Estela; Rodríguez Espino, Benjamín Antonio; Marchat, Laurence A; Sánchez Muñoz, Fausto; Villafaña, Santiago; Hong, Enrique; Meza-Cuenca, Fabián; Mailloux Salinas, Patrick; Bolaños-Jiménez, Francisco; Zambrano, Elena; Arredondo-López, Abel Armando; Bravo, Guadalupe; Huang, Fengyang

2017-08-01

The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R 2 =0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R 2 =0.372, P=0.008). BMI-SDS was mildly associated with leptin (R 2 =0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R 2 =0.136, P=0.007). Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.

Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

PubMed

Lingblom, Christine; Bergquist, Henrik; Johnsson, Marianne; Sundström, Patrik; Quiding-Järbrink, Marianne; Bove, Mogens; Wennerås, Christine

2014-12-01

Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

Extracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) and correlations with clinical staging in euthymic bipolar disorder.

PubMed

Reininghaus, Eva Z; Lackner, Nina; Birner, Armin; Bengesser, Susanne; Fellendorf, Frederike T; Platzer, Martina; Rieger, Alexandra; Queissner, Robert; Kainzbauer, Nora; Reininghaus, Bernd; McIntyre, Roger S; Mangge, Harald; Zelzer, Sieglinde; Fuchs, Dietmar; Dejonge, Silvia; Müller, Norbert

2016-03-01

Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported. The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters. MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2)  = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2)  = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2)  = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms. A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the

The effects of platelet activating factor and retinoic acid on the expression of ELAM-1 and ICAM-1 and the functions of neutrophils

PubMed Central

1995-01-01

Preincubation of pulmonary microvascular endothelial cells (PMVECs) with platelet-activating factor (PAF) for 3.5 h increased the adhesion rate of polymorphonuclear leukocytes (PMNs) to PMVECs from 57.3% to 72.8% (p < 0.01). Preincubation of PMNs with PAF also increased PMN-PMVEC adhesion rate. All-trans retinoic acid (RA) blocked the adherence of untreated PMNs to PAF-pretreated PMVECs but not the adherence of PAF-pretreated PMNs to untreated PMVECs. PAF increased the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selection (ELAM-1) on PMVECs, PMN chemotaxis to zymosan-activated serum and histamine, and PMN aggregation and the release of acid phosphatase from PMNs. Co-incubation of RA inhibited PAF-induced PMN aggregation, the release of acid phosphatase from PMNs, and PMN chemotaxis to zymosan-activated serum and histamine while the expression of ICAM-1 and ELAM-1 did not change. Our results suggest that RA can be used to ameliorate PMN-mediated inflammation. PMID:18475624

Borrelia burgdorferi upregulates the adhesion molecules E-selectin, P-selectin, ICAM-1 and VCAM-1 on mouse endothelioma cells in vitro.

PubMed

Böggemeyer, E; Stehle, T; Schaible, U E; Hahne, M; Vestweber, D; Simon, M M

1994-06-01

In order to obtain more information on processes leading to Borrelia burgdorferi-induced inflammation in the host, we have developed an in vitro model to study the upregulation of cell surface expression of adhesion molecules on endothelial cells by spirochetes. A mouse endothelioma cell line, derived from brain capillaries, bEnd3, was used as indicator population. bEnd3 cells were incubated with preparations of viable, inactivated or sonicated spirochetes and the expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 was monitored by immunocytochemistry and quantified by cell surface ELISA. We show that all three spirochetal preparations are able to upregulate cell surface expression of E-selectin, P-selectin, ICAM-1 and VCAM-1 on bEnd 3 cells in a dose-dependent manner. The kinetics of cell surface expression of the individual adhesion molecules in the presence of Borrelia burgdorferi showed maxima at about 50 h of incubation or later; this was distinct from results obtained with sonicated-preparations of Escherichia coli bacteria or with enterobacterial LPS where peak expression was observed between 4 h and 16 h. The fact that Borrelia burgdorferi does not contain conventional LPS suggests that the mode of induction of adhesion molecules on endothelial cells is influenced by the phenotype of bacteria. At the peak of spirochete-induced cell surface expression of adhesion molecules (approximately 50 h), bEnd3 cells were found to bind cells of a VLA-4+ B lymphoma line (L1-2) much more efficiently than untreated control cells. The binding of L1-2 cells to presensitized bEnd3 cells was significantly inhibited (more than 75%) in the presence of monoclonal antibodies to both VLA-4 and its endothelial counterreceptor VCAM-1. These findings demonstrate that Borrelia burgdorferi organisms are able to induce functionally active adhesion molecules on endothelial cells in vitro and suggest that E-selectin, P-selectin, ICAM-1 and VCAM-1 play an important role in the

Increased plasma soluble adhesion molecules; ICAM-1, VCAM-1, and E-selectin levels in patients with slow coronary flow.

PubMed

Turhan, Hasan; Saydam, Gul Sevim; Erbay, Ali Riza; Ayaz, Selime; Yasar, Ayse Saatci; Aksoy, Yuksel; Basar, Nurcan; Yetkin, Ertan

2006-04-04

Inflammation has been reported to be a major contributing factor to many cardiovascular events. In the present study, we aimed to evaluate plasma soluble adhesion molecules; intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin as possible indicators of endothelial activation or inflammation in patients with slow coronary flow. Study population included 17 patients with angiographically proven normal coronary arteries and slow coronary flow in all three coronary vessels (group I, 11 male, 6 female, mean age=48+/-9 years), and 20 subjects with angiographically proven normal coronary arteries without associated slow coronary flow (group II, 11 male, 9 female, mean age=50+/-8 years). Coronary flow rates of all patients and control subjects were documented by Thrombolysis In Myocardial Infarction frame count (TIMI frame count). All patients in group I had TIMI frame counts greater than two standard deviation above those of control subjects (group II) and, therefore, were accepted as exhibiting slow coronary flow. Serum levels of ICAM-1, VCAM-1, and E-selectin were measured in all patients and control subjects using commercially available ELISA kits. Serum ICAM-1, VCAM-1, and E-selectin levels of patients with slow coronary flow were found to be significantly higher than those of control subjects with normal coronary flow (ICAM-1: 545+/-198 ng/ml vs. 242+/-113 ng/ml respectively, p<0.001, VCAM-1: 2040+/-634 ng/ml vs. 918+/-336 ng/ml respectively, p<0.001, E-selectin: 67+/-9 ng/ml vs. 52+/-8 ng/ml respectively, p<0.001). Average TIMI frame count was detected to be significantly correlated with plasma soluble ICAM-1 (r=0.550, p<0.001), VCAM-1 (r=0.569, p<0.001) and E-selectin (r=0.443, p=0.006). Increased levels of soluble adhesion molecules in patients with slow coronary flow may be an indicator of endothelial activation and inflammation and are likely to be in the causal pathway leading to slow coronary flow.

Cytokines and their association with insulin resistance in obese pregnant women with different levels of physical activity.

PubMed

Nayak, Minakshi; Eekhoff, Marelise E W; Peinhaupt, Miriam; Heinemann, Akos; Desoye, Gernot; van Poppel, Mireille N M

2016-01-01

Cytokines contribute to insulin resistance in pregnancy, but the role of distinct cytokines is not fully understood. To study whether cytokines produced by tissues other than skeletal muscle are associated with glucose and insulin metabolism activity in overweight and obese women and to study whether these associations can be modified by physical activity. A longitudinal study with 44 overweight and obese pregnant women was conducted. Changes in cytokines levels (IFN-γ, IP-10, IL1-α, MIP1-α, adiponectin and leptin) and ICAM1 from early (15wk) to late (32wk) pregnancy were determined. Physical activity was measured objectively with accelerometers. In linear regression models, the associations between (changes in) cytokine levels and fasting glucose, fasting insulin and HOMA-IR were studied. Both IFN-γ and IP-10 levels increased from early to late pregnancy, and adiponectin levels decreased. IFN-γ and IP-10 were positively associated with fasting glucose, whereas IL-1α, ICAM1 and adiponectin were inversely associated with insulin and insulin resistance. The association of IL-1α with insulin and insulin resistance was only found in women with low levels of physical activity. IFN-γ, IP-10, IL1-α, ICAM1, and adiponectin may play a role in glucose and insulin metabolism in pregnancy. The relationship of IL-1α with insulin and insulin resistance might be moderated by levels of physical activity. Further studies are required to confirm the role of these cytokines in glucose and insulin metabolism in obese pregnant women. Copyright © 2015 Elsevier Ltd. All rights reserved.

A fermented bean flour extract downregulates LOX-1, CHOP and ICAM-1 in HMEC-1 stimulated by ox-LDL.

PubMed

Gabriele, Morena; Pucci, Laura; La Marca, Margherita; Lucchesi, Daniela; Della Croce, Clara Maria; Longo, Vincenzo; Lubrano, Valter

2016-01-01

This study focused on an extract from fermented flour from the Lady Joy variety of the common bean Phaseolus vulgaris . The extract, Lady Joy lysate (Lys LJ), is enriched in antioxidant compounds during the fermentation. We assessed it for its protective effect on endothelial cells treated with oxidized-LDL (ox-LDL). The oxidative stress was determined by measuring the contents of thiobarbituric acid-reactive substances and reactive oxygen metabolites. ICAM-1, ET-1 and IL-6 concentrations were assessed using ELISA. LOX-1 and CHOP expression were analyzed using both quantitative RT-PCR and ELISA or western blotting. Ox-LDL treatment induced significant oxidative stress, which was strongly reduced by pre-treatment with the extract. The ox-LDL exposure significantly enhanced ICAM-1, IL-6 and ET-1 levels over basal levels. Lys LJ pre-treatment exerted an inhibitory effect on ox-LDL-induced endothelial activation with ICAM-1 levels comparable to those for the untreated cells. IL-6 and ET-1 production, although reduced, was still significantly higher than for the control. Both LOX-1 and CHOP expression were upregulated after ox-LDL exposure, but this effect was significantly decreased after Lys LJ pre-treatment. Lys LJ alone did not alter the ICAM-1, IL-6 and ET-1 concentrations or CHOP expression, but it did significantly lower the LOX-1 protein level. Our data suggest that Lys LJ is an effective antioxidant that is able to inhibit the oxidation process, but that it is only marginally active against inflammation and ET-1 production in HMEC-1 exposed to ox-LDL.

Melanoma upregulates ICAM-1 expression on endothelial cells through engagement of tumor CD44 with endothelial E-selectin and activation of a PKCα–p38–SP-1 pathway

PubMed Central

Zhang, Pu; Goodrich, Chris; Fu, Changliang; Dong, Cheng

2014-01-01

Cancer metastasis involves multistep adhesive interactions between tumor cells (TCs) and endothelial cells (ECs), but the molecular mechanisms of intercellular communication in the tumor microenvironment remain elusive. Using static and flow coculture systems in conjunction with flow cytometry, we discovered that certain receptors on the ECs are upregulated on melanoma cell adhesion. Direct contact but not separate coculture between human umbilical endothelial cells (HUVECs) and a human melanoma cell line (Lu1205) increased intercellular adhesion molecule 1 (ICAM-1) and E-selectin expression on HUVECs by 3- and 1.5-fold, respectively, compared with HUVECs alone. The nonmetastatic cell line WM35 failed to promote ICAM-1 expression changes in HUVECs on contact. Enzyme-linked immunosorbent assay (ELISA) revealed that EC–TC contact has a synergistic effect on the expression of the cytokines interleukin (IL)-8, IL-6, and growth-related oncogene α (Gro-α). By using E-selectin cross-linking and beads coated with CD44 immunopurified from Lu1205 cells, we showed that CD44/selectin ligation was responsible for the ICAM-1 up-regulation on HUVECs. Protein kinase Cα (PKC-α) activation was found to be the downstream target of the CD44/selectin-initiated signaling, as ICAM-1 elevation was inhibited by siRNA targeting PKCα or a dominant negative form of PKCα (PKCα DN). Western blot analysis and electrophoretic mobility shift assays (EMSAs) showed that TC–EC contact mediated p38 phosphorylation and binding of the transcription factor SP-1 to its regulation site. In conclusion, CD44/selectin binding signals ICAM-1 up-regulation on the EC surface through a PKCα–p38–SP-1 pathway, which further enhances melanoma cell adhesion to ECs during metastasis.—Zhang, P., Goodrich, C., Fu, C., Dong, C. Melanoma upregulates ICAM-1 expression on ECs through engagement of tumor CD44 with endothelial E-selectin and activation of a PKCα–p38–SP-1 pathway. PMID:25138157

Resistance of Feather-Associated Bacteria to Intermediate Levels of Ionizing Radiation near Chernobyl.

PubMed

Ruiz-González, Mario Xavier; Czirják, Gábor Árpád; Genevaux, Pierre; Møller, Anders Pape; Mousseau, Timothy Alexander; Heeb, Philipp

2016-03-15

Ionizing radiation has been shown to produce negative effects on organisms, although little is known about its ecological and evolutionary effects. As a study model, we isolated bacteria associated with feathers from barn swallows Hirundo rustica from three study areas around Chernobyl differing in background ionizing radiation levels and one control study site in Denmark. Each bacterial community was exposed to four different γ radiation doses ranging from 0.46 to 3.96 kGy to test whether chronic exposure to radiation had selected for resistant bacterial strains. Experimental radiation duration had an increasingly overall negative effect on the survival of all bacterial communities. After exposure to γ radiation, bacteria isolated from the site with intermediate background radiation levels survived better and produced more colonies than the bacterial communities from other study sites with higher or lower background radiation levels. Long-term effects of radiation in natural populations might be an important selective pressure on traits of bacteria that facilitate survival in certain environments. Our findings indicate the importance of further studies to understand the proximate mechanisms acting to buffer the negative effects of ionizing radiation in natural populations.

Resistance of Feather-Associated Bacteria to Intermediate Levels of Ionizing Radiation near Chernobyl

PubMed Central

Ruiz-González, Mario Xavier; Czirják, Gábor Árpád; Genevaux, Pierre; Møller, Anders Pape; Mousseau, Timothy Alexander; Heeb, Philipp

2016-01-01

Ionizing radiation has been shown to produce negative effects on organisms, although little is known about its ecological and evolutionary effects. As a study model, we isolated bacteria associated with feathers from barn swallows Hirundo rustica from three study areas around Chernobyl differing in background ionizing radiation levels and one control study site in Denmark. Each bacterial community was exposed to four different γ radiation doses ranging from 0.46 to 3.96 kGy to test whether chronic exposure to radiation had selected for resistant bacterial strains. Experimental radiation duration had an increasingly overall negative effect on the survival of all bacterial communities. After exposure to γ radiation, bacteria isolated from the site with intermediate background radiation levels survived better and produced more colonies than the bacterial communities from other study sites with higher or lower background radiation levels. Long-term effects of radiation in natural populations might be an important selective pressure on traits of bacteria that facilitate survival in certain environments. Our findings indicate the importance of further studies to understand the proximate mechanisms acting to buffer the negative effects of ionizing radiation in natural populations. PMID:26976674

Development of TRAIL Resistance by Radiation-Induced Hypermethylation of DR4 CpG Island in Recurrent Laryngeal Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jong Cheol; Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan; Lee, Won Hyeok

2014-04-01

Purpose: There are limited therapeutic options for patients with recurrent head and neck cancer after radiation therapy failure. To assess the use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) as a salvage chemotherapeutic agent for recurrent cancer after radiation failure, we investigated the effect of clinically relevant cumulative irradiation on TRAIL-induced apoptosis. Methods and Materials: Using a previously established HN3 cell line from a laryngeal carcinoma patient, we generated a chronically irradiated HN3R isogenic cell line. Viability and apoptosis in HN3 and HN3R cells treated with TRAIL were analyzed with MTS and PI/annexin V-FITC assays. Western blotting and flow cytometry weremore » used to determine the underlying mechanism of TRAIL resistance. DR4 expression was semiquantitatively scored in a tissue microarray with 107 laryngeal cancer specimens. Methylation-specific polymerase chain reaction and bisulfite sequencing for DR4 were performed for genomic DNA isolated from each cell line. Results: HN3R cells were more resistant than HN3 cells to TRAIL-induced apoptosis because of significantly reduced levels of the DR4 receptor. The DR4 staining score in 37 salvage surgical specimens after radiation failure was lower in 70 surgical specimens without radiation treatment (3.03 ± 2.75 vs 5.46 ± 3.30, respectively; P<.001). HN3R cells had a methylated DR4 CpG island that was partially demethylated by the DNA demethylating agent 5-aza-2′-deoxycytidine. Conclusion: Epigenetic silencing of the TRAIL receptor by hypermethylation of a DR4 CpG island might be an underlying mechanism for TRAIL resistance in recurrent laryngeal carcinoma treated with radiation.« less

Novel radiation-resistant glass fiber/epoxy composite for cryogenic insulation system

NASA Astrophysics Data System (ADS)

Wu, Z. X.; Zhang, H.; Yang, H. H.; Chu, X. X.; Li, L. F.

2010-08-01

A new radiation-resistant epoxy resin system was developed that has low viscosity and long working time at 45 °C. The system consists of triglycidyl-p-aminophenol (TGPAP) epoxide, isopropylidenebisphenol bis[(2-glycidyloxy-3-n-butoxy)-1-propylether] (IPBE) epoxide and diethyl toluene diamine (DETD). Boron-free glass fiber composites of epoxy resin with different ratio of TGPAP/IPBE/DETD were prepared by vacuum press impregnation. The ratio of TGPAP/IPBE affected the working time and the viscosity at the impregnation. The mechanical properties of the composites at 300 K and at 77 K were measured before and after 60Co γ-ray irradiation of 1 MGy at ambient temperature. The γ-ray radiation scarcely affected the properties of the composites.

Tetrandrine suppresses lung cancer growth and induces apoptosis, potentially via the VEGF/HIF-1α/ICAM-1 signaling pathway

PubMed Central

Chen, Zhuo; Zhao, Liang; Zhao, Feng; Yang, Guanghai; Wang, Jian Jun

2018-01-01

The present study investigated the effect of tetrandrine on lung cancer cell growth and apoptosis, and its possible underlying molecular mechanism. A549 human lung cancer cells were incubated with between 2.5 and 10 µM tetrandrine for 12, 24 and 48 h, following which the effect of tetrandrine on cell viability and apoptosis were assessed using an MTT assay and flow cytometry. ELISA and western blotting were used to analyze VEGF activity, and the expression of poly (ADP-ribose) polymerase (PARP), phosphorylated protein kinase B (Akt), Bcl-2-associated X protein (Bax), hypoxia inducible factor (HIF)-1α and inter-cellular adhesion molecule-1 (ICAM-1). Tetrandrine effectively suppressed the growth of and induced apoptosis in A549 lung cancer cells. The expression of PARP, Bax, intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) was significantly upregulated, and the phosphorylation of Akt and expression of HIF-1α was significantly suppressed in A549 lung cancer cells. Therefore, tetrandrine may suppress cell viability and induce apoptosis via the VEGF/HIF-1α/ICAM-1 signaling pathway. PMID:29849794

Involvement of adhesion molecules (CD11a-ICAM-1) in vascular endothelial cell injury elicited by PMA-stimulated neutrophils.

PubMed

Fujita, H; Morita, I; Murota, S

1991-06-14

Protective effect of anti-CD11a and anti-ICAM-1 antibodies on the cytotoxicity induced by PMA-stimulated neutrophils was studied using cultured endothelial cells isolated from bovine carotid artery. Anti-CD11a antibody and anti-ICAM-1 antibody inhibited the endothelial cell injury induced by the activated neutrophils in a dose dependent manner. On the other hand, both antibodies themselves had no effect on either the luminol chemiluminescence released out of the activated neutrophils or the adhesion of the neutrophils to the endothelial cell monolayer. These data suggest that these adhesion molecules play some important roles in the vascular endothelial cell injury elicited by activated neutrophils.

Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell.

PubMed

Cho, Young S; Kim, Chan H; Ha, Tae S; Ahn, Hee Y

2015-11-18

Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation.

Resistivity, carrier trapping, and polarization phenomenon in semiconductor radiation detection materials

NASA Astrophysics Data System (ADS)

Du, Mao-Hua; Biswas, Koushik; Singh, David J.

2012-10-01

In this paper, we report theoretical studies of native defects and dopants in a number of room-temperature semiconductor radiation detection materials, i.e., CdTe, TlBr, and Tl6SeI4. We address several important questions, such as what causes high resistivity in these materials, what explains good μτ product (carrier mobility-lifetime product) in soft-lattice ionic compounds that have high defect density, and how to obtain high resistivity and low carrier trapping simultaneously. Our main results are: (1) shallow donors rather than deep ones are responsible for high resistivity in high-quality detectorgrade CdTe; (2) large dielectric screening and the lack of deep levels from low-energy native defects may contribute to the good μτ products for both electrons and holes in TlBr; (3) the polarization phenomenon in Tl6SeI4 is expected to be much reduced compared to that in TlBr.

Evaluation of a 3D diamond detector for medical radiation dosimetry

NASA Astrophysics Data System (ADS)

Kanxheri, K.; Servoli, L.; Oh, A.; Munoz Sanchez, F.; Forcolin, G. T.; Murphy, S. A.; Aitkenhead, A.; Moore, C. J.; Morozzi, A.; Passeri, D.; Bellini, M.; Corsi, C.; Lagomarsino, S.; Sciortino, S.

2017-01-01

Synthetic diamond has several properties that are particularly suited to applications in medical radiation dosimetry. It is tissue equivalent, not toxic and shows a high resistance to radiation damage, low leakage current and stability of response. It is an electrical insulator, robust and realizable in small size; due to these features there are several examples of diamond devices, mainly planar single-crystalline chemical vapor depositation (sCVD) diamond, used for relative dose measurement in photon beams. Thanks to a new emerging technology, diamond devices with 3-dimensional structures are produced by using laser pulses to create graphitic paths in the diamond bulk. The necessary bias voltage to operate such detector decreases considerably while the signal response and radiation resistance increase. In order to evaluate the suitability of this new technology for measuring the dose delivered by radiotherapy beams in oncology a 3D polycrystalline (pCVD) diamond detector designed for single charged particle detection has been tested and the photon beam profile has been studied. The good linearity and high sensitivity to the dose observed in the 3D diamond, opens the way to the possibility of realizing a finely segmented device with the potential for dose distribution measurement in a single exposure for small field dosimetry that nowadays is still extremely challenging.

UV light-induced survival response in a highly radiation-resistant isolate of the Moraxella-acinetobacter group

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keller, L.C.; Thompson, T.L.; Maxcy, R.B.

1982-02-01

A highly radiation-resistant member of the Moraxella-Acinetobacter group, isolate 4, obtained from meat, was studied to determine the effect of preexposure to UV radiation on subsequent UV light resistance. Cultures that were preexposed to UV light and incubated for a short time in plate count broth exhibited increased survival of a UV light challenge dose. This response was inhibited in the presence of chloramphenicol. Frequencies of mutation to streptomycin, trimethoprim, and sulfanilamide resistance remained the same after the induction of this survival response and were not altered by treatment with mutagens, with the exception of mutation to streptomycin resistance aftermore » ..gamma..-irradiation or nitrosoguanidine or methyl methane sulfonate treatment. The results indicated that isolate 4 has a UV light-inducible UV light resistance mechanism which is not associated with increased mutagenesis. The characteristics of the radiation resistance response in this organism are similar to those of certain other common food contaminants. Therefore, considered as part of the total microflora of meat, isolate 4 and the other radiation-resistant Moraxella-Acinetobacter isolates should not pose unique problems in a proposed radappertizaton process.« less

Characterization of radiation-resistant vegetative bacteria in beef.

PubMed

Welch, A B; Maxcy, R B

1975-08-01

Ground beef contains numerous microorganisms of various types. The commonly recognized bacteria are associated with current problems of spoilage. Irradiation, however, contributes a new factor through selective destruction of the microflora. The residual microorganisms surviving a nonsterilizing dose are predominantly gram-negative coccobacilli. Various classifications have been given, e.g., Moraxella, Acinetobacter, Achromobacter, etc. For a more detailed study of these radiation-resistant bacteria occurring in ground beef, an enrichment procedure was used for isolation. By means of morphological and biochemical tests, most of the isolates were found to be Moraxella, based on current classifications. The range of growth temperatures was from 2 to 50 C. These bacteria were relatively heat sensitive, e.g., D10 of 5.4 min at 70 C or less. The radiation resistance ranged from D10 values of 273 to 2,039 krad. Thus, some were more resistant than any presently recognized spores. A reference culture of Moraxella osloensis was irradiated under conditions comparable to the enrichment procedure used with the ground beef. The only apparent changes were in morphology and penicillin sensitivity. However, after a few subcultures these bacteria reverted to the characteristics of the parent strain. Thus, it is apparent that these isolates are a part of the normal flora of ground beef and not aberrant forms arising from the irradiation procedure. The significance, if any, of these bacteria is not presently recognized.

Archway for Radiation and Micrometeorite Occurrence Resistance

NASA Technical Reports Server (NTRS)

Giersch, Louis R.

2012-01-01

The environmental conditions of the Moon require mitigation if a long-term human presence is to be achieved for extended periods of time. Radiation, micrometeoroid impacts, high-velocity debris, and thermal cycling represent threats to crew, equipment, and facilities. For decades, local regolith has been suggested as a candidate material to use in the construction of protective barriers. A thickness of roughly 3m is sufficient protection from both direct and secondary radiation from cosmic rays and solar protons; this thickness is sufficient to reduce radiation exposure even during solar flares. NASA has previously identified a need for innovations that will support lunar habitats using lightweight structures because the reduction of structural mass translates directly into additional up and down mass capability that would facilitate additional logistics capacity and increased science return for all mission phases. The development of non-pressurized primary structures that have synergy with the development of pressurized structures is also of interest. The use of indigenous or in situ materials is also a well-known and active area of research that could drastically improve the practicality of human exploration beyond low-Earth orbit. The Archway for Radiation and Micrometeorite Occurrence Resistance (ARMOR) concept is a new, multifunctional structure that acts as radiation shielding and micrometeorite impact shielding for long-duration lunar surface protection of humans and equipment. ARMOR uses a combination of native regolith and a deployed membrane jacket to yield a multifunctional structure. ARMOR is a robust and modular system that can be autonomously assembled on-site prior to the first human surface arrival. The system provides protection by holding a sufficiently thick (3 m) archshaped shell of local regolith around a central cavity. The regolith is held in shape by an arch-shaped jacket made of strong but deployable material. No regolith processing is

Autophagy contributes to resistance of tumor cells to ionizing radiation.

PubMed

Chaachouay, Hassan; Ohneseit, Petra; Toulany, Mahmoud; Kehlbach, Rainer; Multhoff, Gabriele; Rodemann, H Peter

2011-06-01

Autophagy signaling is a novel important target to improve anticancer therapy. To study the role of autophagy on resistance of tumor cells to ionizing radiation (IR), breast cancer cell lines differing in their intrinsic radiosensitivity were used. Breast cancer cell lines MDA-MB-231 and HBL-100 were examined with respect to clonogenic cell survival and induction of autophagy after radiation exposure and pharmacological interference of the autophagic process. As marker for autophagy the appearance of LC3-I and LC3-II proteins was analyzed by SDS-PAGE and Western blotting. Formation of autophagic vacuoles was monitored by immunofluorescence staining of LC3. LC3-I and LC3-II formation differs markedly in radioresistant MDA-MB-231 versus radiosensitive HBL-100 cells. Western blot analyses of LC3-II/LC3-I ratio indicated marked induction of autophagy by IR in radioresistant MDA-MB-231 cells, but not in radiosensitive HBL-100 cells. Indirect immunofluorescence analysis of LC3-II positive vacuoles confirmed this differential effect. Pre-treatment with 3-methyladenine (3-MA) antagonized IR-induced autophagy. Likewise, pretreatment of radioresistant MDA-231 cells with autophagy inhibitors 3-MA or chloroquine (CQ) significantly reduced clonogenic survival of irradiated cells. Our data clearly indicate that radioresistant breast tumor cells show a strong post-irradiation induction of autophagy, which thus serves as a protective and pro-survival mechanism in radioresistance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Size and targeting to PECAM vs ICAM control endothelial delivery, internalization and protective effect of multimolecular SOD conjugates.

PubMed

Shuvaev, Vladimir V; Muro, Silvia; Arguiri, Evguenia; Khoshnejad, Makan; Tliba, Samira; Christofidou-Solomidou, Melpo; Muzykantov, Vladimir R

2016-07-28

Controlled endothelial delivery of SOD may alleviate abnormal local surplus of superoxide involved in ischemia-reperfusion, inflammation and other disease conditions. Targeting SOD to endothelial surface vs. intracellular compartments is desirable to prevent pathological effects of external vs. endogenous superoxide, respectively. Thus, SOD conjugated with antibodies to cell adhesion molecule PECAM (Ab/SOD) inhibits pro-inflammatory signaling mediated by endogenous superoxide produced in the endothelial endosomes in response to cytokines. Here we defined control of surface vs. endosomal delivery and effect of Ab/SOD, focusing on conjugate size and targeting to PECAM vs. ICAM. Ab/SOD enlargement from about 100 to 300nm enhanced amount of cell-bound SOD and protection against extracellular superoxide. In contrast, enlargement inhibited endocytosis of Ab/SOD and diminished mitigation of inflammatory signaling of endothelial superoxide. In addition to size, shape is important: endocytosis of antibody-coated spheres was more effective than that of polymorphous antibody conjugates. Further, targeting to ICAM provides higher endocytic efficacy than targeting to PECAM. ICAM-targeted Ab/SOD more effectively mitigated inflammatory signaling by intracellular superoxide in vitro and in animal models, although total uptake was inferior to that of PECAM-targeted Ab/SOD. Therefore, both geometry and targeting features of Ab/SOD conjugates control delivery to cell surface vs. endosomes for optimal protection against extracellular vs. endosomal oxidative stress, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Mast Cell Activation Protects Cornea by Promoting Neutrophil Infiltration via Stimulating ICAM-1 and Vascular Dilation in Fungal Keratitis.

PubMed

Xie, Yanting; Zhang, Hongmin; Liu, Susu; Chen, Guoming; He, Siyu; Li, Zhijie; Wang, Liya

2018-05-30

The role of mast cells (MCs) in fungal infection is largely unknown. This study was to explore a protective role and mechanism of MCs in fungal keratitis. Experimental fungal keratitis (FK) mouse model was developed. Mice untreated (UT) or receiving corneal wound without fungal infection (Mock) were used as controls. Large number of connective tissue MCs was found in normal mice. MC activation with degranulation was largely observed, and the percentage of degranulated/total cells was high in FK. Dilated limbal vasculature with increased permeability, as well as largely infiltrated neutrophils with stimulated ICAM-1 protein levels were observed in corneas of FK mice, when compared with Mock and UT mice. Interestingly, pretreatment with cromolyn sodium (Block) significantly blocked MC degranulation, dramatically suppressed vascular dilation and permeability, and markedly reduced neutrophil infiltration with lower ICAM-1 levels in FK mice at 6-24 hours. Furthermore, the Block mice manifested prolonged disease course, increased pathological damage, and vigorous fungus growth, with much higher corneal perforation rate than FK mice at 72 h. These findings reveal a novel phenomenon that MCs play a vital role in protecting cornea against fungal infection through degranulation that promotes neutrophil infiltration via stimulating ICAM-1 production and limbal vascular dilation and permeability.

A separate role for ICAM-1 and fluid shear in regulating leukocyte interactions with straight regions of venular wall and venular convergences

PubMed Central

Sumagin, Ronen; Lamkin-Kennard, Kathleen A.; Sarelius, Ingrid H

2011-01-01

Objective Variation in expression of adhesion molecules plays a key role in regulating leukocyte behavior, but the contribution of fluid shear to these interactions cannot be ignored. Here we dissected the effects of each of these factors on leukocyte behavior in different venular regions. Methods Leukocyte behavior was quantified in blood perfused microvascular networks in anesthetized mouse cremaster muscle using intravital confocal microscopy. ICAM-1 expression and fluid shear rate were quantified using ICAM-1 fluorescent labeling, fluorescent particle tracking, and computational fluid dynamics. Results TNFα-induced an increase in ICAM-1 expression, and abolished the differences observed among control venules of different sizes. Consequently, leukocyte adhesion was increased to a similar level across all vessel sizes (5.1±0.46 leukocytes/100μm vs. 2.1±0.47 [control]), but remained significantly higher in venular convergences (7.8±0.4). Leukocyte transmigration occurred primarily in the smallest venules and venular convergences (23.9±5.1 and 31.9±2.7 leukocytes/10,000μm2 tissue, respectively). In venular convergences the two inlet vessels are predicted to create a region of low velocity, increasing leukocyte adhesion probability. Conclusions In straight regions of different sized venules the variability in ICAM-1 expression accounts for the differences in leukocyte behavior; in converging regions, fluid shear potentially has a greater effect on leukocyte-EC interactions. PMID:19468960

Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1.

PubMed

Xie, Fang; Li, Zhi-Ping; Wang, Hong-Wei; Fei, Xiang; Jiao, Zi-Yu; Tang, Wen-Bo; Tang, Jie; Luo, Yu-Kun

2016-01-01

To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle's maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6-7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level.

ICAM-1 is necessary for epithelial recruitment of gammadelta T cells and efficient corneal wound healing.

USDA-ARS?s Scientific Manuscript database

Wound healing and inflammation are both significantly reduced in mice that lack gammadelta T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in gammadelta T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epi...

Radiation-Resistant Hybrid Lotus Effect for Achieving Photoelectrocatalytic Self-Cleaning Anticontamination Coatings

NASA Technical Reports Server (NTRS)

Taylor, Edward W.; Pirich, Ronald G.

2011-01-01

An experiment involving radiation-resistant hydrophobic coatings is planned for space exposure and experimental testing on the International Space Station (ISS) in 2011. The Lotus biocide coatings are designed for supporting space exploration missions. This innovation is an antibacterial, anti-contamination, and self-cleaning coating that uses nano-sized semiconductor semimetal oxides to neutralize biological pathogens and toxic chemicals, as well as to mitigate dust accumulation (see figure). The Lotus biocide coating is thin (approximately microns thick), lightweight, and the biocide properties will not degrade with time or exposure to biological or chemical agents. The biocide is stimulated chemically (stoichiometric reaction) through exposure to light (photocatalysis), or by an applied electric field (electrocatalysis). The hydrophobic coating samples underwent preliminary high-energy proton and alpha-ray (helium ion) irradiations at the Lawrence Berkeley National Laboratory 88" cyclotron and demonstrated excellent radiation resistance for a portion of the Galactic Cosmic Ray (GRC) and Solar Proton spectrum. The samples will undergo additional post-flight studies when returned to Earth to affirm further the radiation resistance properties of the space exposed coatings.

PREFACE: International Conference on Advanced Materials (ICAM 2015)

NASA Astrophysics Data System (ADS)

El-Khateeb, Mohammad Y.

2015-10-01

It is with great pleasure to welcome you to the "International Conference of Advanced Materials ICAM 2015" that will take place at Jordan University of Science and Technology (JUST), Irbid, Jordan. This year, the conference coincides with the coming of spring in Jordan; we hope the participants will enjoy the colors and fragrance of April in Jordan. The call for papers attracted submissions of over a hundred abstracts from twenty one different countries. These papers are going to be classified under four plenary lectures, fifteen invited papers, thirty five oral presentations and more than sixty posters covering the different research areas of the conference. The ICAM conference focuses on new advances in research in the field of materials covering chemical, physical and biological aspects. ICAM includes representatives from academia, industry, governmental and private sectors. The plenary and invited speakers will present, discuss, promote and disseminate research in all fields of advanced materials. Topics range from synthesis, applications, and solid state to nano-materials. In addition, talented junior investigators will present their best ongoing research at a poster session. We have also organized several workshops contiguous to the main conference, such as the one-day workshop on "Particle Surface Modification for Improved Applications". The purpose of this short course was to introduce interested materials technologists to several methodologies that have been developed to modify the surfaces of particulate matter. Moreover, a pre-conference workshop on "Communication in Science" was conducted for young scientists. The main goal of this workshop was to train young scientists in matters of interdisciplinary scientific communications. In addition to the scientific program, the attendees will have a chance to discover the beauty of Jordan, a land of rich history and varied culture. Numerous social events that will provide opportunities to renew old contacts and

Role of Mn2+ and compatible solutes in the radiation resistance of thermophilic bacteria and archaea.

PubMed

Webb, Kimberly M; DiRuggiero, Jocelyne

2012-01-01

Radiation-resistant bacteria have garnered a great deal of attention from scientists seeking to expose the mechanisms underlying their incredible survival abilities. Recent analyses showed that the resistance to ionizing radiation (IR) in the archaeon Halobacterium salinarum is dependent upon Mn-antioxidant complexes responsible for the scavenging of reactive oxygen species (ROS) generated by radiation. Here we examined the role of the compatible solutes trehalose, mannosylglycerate, and di-myo-inositol phosphate in the radiation resistance of aerobic and anaerobic thermophiles. We found that the IR resistance of the thermophilic bacteria Rubrobacter xylanophilus and Rubrobacter radiotolerans was highly correlated to the accumulation of high intracellular concentration of trehalose in association with Mn, supporting the model of Mn(2+)-dependent ROS scavenging in the aerobes. In contrast, the hyperthermophilic archaea Thermococcus gammatolerans and Pyrococcus furiosus did not contain significant amounts of intracellular Mn, and we found no significant antioxidant activity from mannosylglycerate and di-myo-inositol phosphate in vitro. We therefore propose that the low levels of IR-generated ROS under anaerobic conditions combined with highly constitutively expressed detoxification systems in these anaerobes are key to their radiation resistance and circumvent the need for the accumulation of Mn-antioxidant complexes in the cell.

Unraveling Fungal Radiation Resistance Regulatory Networks through the Genome-Wide Transcriptome and Genetic Analyses of Cryptococcus neoformans

PubMed Central

Jung, Kwang-Woo; Yang, Dong-Hoon; Kim, Min-Kyu; Seo, Ho Seong

2016-01-01

ABSTRACT The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation. Particularly, deletion of recombinase RAD51 and two DNA-dependent ATPase genes, RAD54 and RDH54, increased cellular susceptibility to both gamma radiation and DNA-damaging agents. A variety of oxidative stress response genes were also upregulated. Among them, sulfiredoxin contributed to gamma radiation resistance in a peroxiredoxin/thioredoxin-independent manner. Furthermore, we found that genes involved in molecular chaperone expression, ubiquitination systems, and autophagy were induced, whereas genes involved in the biosynthesis of proteins and fatty acids/sterols were downregulated. Most importantly, we discovered a number of novel C. neoformans genes, the expression of which was modulated by gamma radiation exposure, and their deletion rendered cells susceptible to gamma radiation exposure, as well as DNA damage insults. Among these genes, we found that a unique transcription factor containing the basic leucine zipper domain, named Bdr1, served as a regulator of the gamma radiation resistance of C. neoformans by controlling expression of DNA repair genes, and its expression was regulated by the evolutionarily conserved DNA damage response protein kinase Rad53. Taken together, the current transcriptome and functional analyses contribute to the understanding of the unique molecular mechanism of the radiation-resistant fungus C. neoformans. PMID:27899501

Characterization of radiation-resistant vegetative bacteria in beef

DOE Office of Scientific and Technical Information (OSTI.GOV)

Welch, A.B.; Maxcy, R.B.

1975-08-01

Ground beef contains numerous microorganisms of various types. The commonly recognized bacteria are associated with current problems of spoilage. Irradiation, however, contributes a new factor through selective destruction of the microflora. The residual microorganisms surviving a nonsterilizing dose are predominantly gram-negative coccobacilli. Various classifications have been given, e.g., Moraxella, Acinetobacter, Achromobacter, etc. For a more detailed study of these radiation-resistant bacteria occurring in ground beef, an enrichment procedure was used for isolation. By means of morphological and biochemical tests, most of the isolates were found to be Moraxella, based on current classifications. The range of growth temperatures was from 2more » to 50 C. These bacteria were relatively heat sensitive, e.g., D$sub 10$ of 5.4 min at 70$sup 0$C or less. The radiation resistance ranged from D$sub 10$ values of 273 to 2,039 krad. Thus, some were more resistant than any presently recognized spores. A reference culture of Moraxella osloensis was irradiated under conditions comparable to the enrichment procedure used with the ground beef. The only apparent changes were in morphology and penicillin sensitivity. However, after a few subcultures these bacteria reverted to the characteristics of the parent strain. Thus, it is apparent that these isolates are a part of the normal flora of ground beef and not aberrant forms arising from the irradiation procedure. The significance, if any, of these bacteria is not presently recognized. (auth)« less

Prediction of Ionizing Radiation Resistance in Bacteria Using a Multiple Instance Learning Model.

PubMed

Aridhi, Sabeur; Sghaier, Haïtham; Zoghlami, Manel; Maddouri, Mondher; Nguifo, Engelbert Mephu

2016-01-01

Ionizing-radiation-resistant bacteria (IRRB) are important in biotechnology. In this context, in silico methods of phenotypic prediction and genotype-phenotype relationship discovery are limited. In this work, we analyzed basal DNA repair proteins of most known proteome sequences of IRRB and ionizing-radiation-sensitive bacteria (IRSB) in order to learn a classifier that correctly predicts this bacterial phenotype. We formulated the problem of predicting bacterial ionizing radiation resistance (IRR) as a multiple-instance learning (MIL) problem, and we proposed a novel approach for this purpose. We provide a MIL-based prediction system that classifies a bacterium to either IRRB or IRSB. The experimental results of the proposed system are satisfactory with 91.5% of successful predictions.

Bilirubin Prevents Atherosclerotic Lesion Formation in Low-Density Lipoprotein Receptor-Deficient Mice by Inhibiting Endothelial VCAM-1 and ICAM-1 Signaling.

PubMed

Vogel, Megan E; Idelman, Gila; Konaniah, Eddy S; Zucker, Stephen D

2017-04-01

Numerous epidemiological studies support an inverse association between serum bilirubin levels and the incidence of cardiovascular disease; however, the mechanism(s) by which bilirubin may protect against atherosclerosis is undefined. The goals of the present investigations were to assess the ability of bilirubin to prevent atherosclerotic plaque formation in low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice and elucidate the molecular processes underlying this effect. Bilirubin, at physiological concentrations (≤20 μmol/L), dose-dependently inhibits THP-1 monocyte migration across tumor necrosis factor α-activated human umbilical vein endothelial cell monolayers without altering leukocyte binding or cytokine production. A potent antioxidant, bilirubin effectively blocks the generation of cellular reactive oxygen species induced by the cross-linking of endothelial vascular cell adhesion molecule 1 (VCAM-1) or intercellular adhesion molecule 1 (ICAM-1). These findings were validated by treating cells with blocking antibodies or with specific inhibitors of VCAM-1 and ICAM-1 signaling. When administered to Ldlr -/- mice on a Western diet, bilirubin (30 mg/kg intraperitoneally) prevents atherosclerotic plaque formation, but does not alter circulating cholesterol or chemokine levels. Aortic roots from bilirubin-treated animals exhibit reduced lipid and collagen deposition, decreased infiltration of monocytes and lymphocytes, fewer smooth muscle cells, and diminished levels of chlorotyrosine and nitrotyrosine, without changes in VCAM-1 or ICAM-1 expression. Bilirubin suppresses atherosclerotic plaque formation in Ldlr -/- mice by disrupting endothelial VCAM-1- and ICAM-1-mediated leukocyte migration through the scavenging of reactive oxygen species signaling intermediaries. These findings suggest a potential mechanism for the apparent cardioprotective effects of bilirubin. © 2017 The Authors. Published on behalf of the American Heart Association, Inc

Theory of heat transfer and hydraulic resistance of oil radiators

NASA Technical Reports Server (NTRS)

Mariamov, N B

1942-01-01

In the present report the coefficients of heat transfer and hydraulic resistance are theoretically obtained for the case of laminar flow of a heated viscous liquid in a narrow rectangular channel. The results obtained are applied to the computation of oil radiators, which to a first approximation may be considered as made up of a system of such channels. In conclusion, a comparison is given of the theoretical with the experimental results obtained from tests on airplane oil radiators.

Impact of Blood Vessel Quantity and Vascular Expression of CD133 and ICAM-1 on Survival of Glioblastoma Patients

PubMed Central

Kase, Marju; Saretok, Mikk; Adamson-Raieste, Aidi; Kase, Sandra; Niinepuu, Kristi; Vardja, Markus; Asser, Toomas

2017-01-01

Glioblastoma (GB) is the most angiogenic tumor. Nevertheless, antiangiogenic therapy has not shown significant clinical efficacy. The aim of this study was to assess blood vessel characteristics on survival of GB patients. Surgically excised GB tissues were histologically examined for overall proportion of glomeruloid microvascular proliferation (MP) and the total number of blood vessels. Also, immunohistochemical vascular staining intensities of CD133 and ICAM-1 were determined. Vessel parameters were correlated with patients' overall survival. The survival time depended on the number of blood vessels (p = 0.03) but not on the proportion of MP. Median survival times for patients with low (3–14.7). Also, median survival times for patients with low (3–13.7). In contrast, the staining intensity of vascular ICAM-1 did not affect survival. In multivariate analysis, the number of blood vessels emerged as an independent predictor for longer overall survival (HR: 2.4, 95% CI: 1.2–5.0, p = 0.02). For success in antiangiogenic therapy, better understanding about tumor vasculature biology is needed. PMID:29250531

Comparison of sVCAM-1 and sICAM-1 levels in maternal serum and vaginal secretion between pregnant women with preterm prelabour ruptures of membranes and healthy pregnant women.

PubMed

Sak, Sibel; Barut, Mert; Incebiyik, Adnan; Ağaçayak, Elif; Kirmit, Adnan; Koyuncu, Ismail; Sak, Muhammet

2017-11-02

The study aims to evaluate the maternal serum and the vaginal fluid levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecular (sICAM-1) in pregnant women complicated by preterm prelabour ruptures of membranes (PPROM). The prospective case control study included 34 pregnant women with PPROM and 34 healthy pregnant women. Patients with additional diseases, a smoking habit and vaginal bleeding, as well as those using antibiotics, during the study period were not included in the study. Cervicovaginal fluid and serum samples were taken during the patients' admission. The demographic data, maternal serum and vaginal fluid sVCAM-1 and sICAM-1, C reactive protein (CRP) and leukocyte counts were noted for all pregnant women included in the study. The sVCAM-1 and sICAM-1 levels were measured by enzyme-linked immunosorbent assay kits. In pregnant women with PPROM, the serum leukocyte (mean ± SD =11.41 ± 1.067 versus 9.18 ± 1.56, p < .0001), serum sVCAM-1 (median 771.20 versus 704.60 ng/ml, p < .001), sICAM-1 (mean ± SD 213.10 ± 35.59 ng/ml versus 188.11 ± 37.35 ng/ml, p = .06), vaginal sVCAM-1 (median 208.00 versus 140.20 ng/ml, p = .014) and sICAM-1 (mean ± SD 32.32 ± 6.49 ng/ml versus 24.87 ± 6.79 ng/ml, p < .001) values were found to be significantly higher in pregnant women with PPROM than in healthy pregnant women. A positive and significant correlation was observed between the leukocyte count and the vaginal sVCAM-1 level (r = 0.850; p < .001). To the best of our knowledge, this is the first study evaluating the levels of sICAM-1 in maternal serum in pregnant women with PPROM. The maternal serum and vaginal fluid sVCAM-1 and sICAM-1 levels can be used as biochemical markers supporting the PPROM diagnosis because of the increase in both maternal serum and vaginal fluid sVCAM-1 and sICAM-1 levels in pregnant women with PPROM.

High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation.

PubMed

Huang, Xiaoqin; He, Dan; Ming, Jia; He, Yubin; Zhou, Champion; Ren, Hui; He, Xin; Wang, Chenguang; Jin, Jingru; Ji, Liang; Willard, Belinda; Pan, Bing; Zheng, Lemin

2016-02-01

Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis

Radiation-Resistant Micrococcus luteus SC1204 and Its Proteomics Change Upon Gamma Irradiation.

PubMed

Deng, Wuyuan; Yang, Yang; Gao, Peng; Chen, Hao; Wen, Wenting; Sun, Qun

2016-06-01

To explore the radiation-resistance mechanisms in bacteria, a radiation-resistant strain SC1204 was isolated from the surrounding area of a (60)Co-γ radiation facility. SC1204 could survive up to 8 kGy dose of gamma irradiation and was identified as Micrococcus luteus by phylogenetic analysis of 16S rRNA gene sequences. Its proteomic changes under 2-kGy irradiation were examined by two-dimensional electrophoresis followed by MALDI-TOF-TOF/MS analysis. The results showed that at least 24 proteins displayed significant changes (p < 0.05) at expression level under the radiation stress, among which 22 were successfully identified and classified into the major functional categories of metabolism, energy production and conservation, translation, ribosomal structure, and biogenesis. Among these proteins, leucyl aminopeptidase involved in synthesis of glutathione was the most abundant induced protein during postirradiation recovery, indicating that anti-oxidation protection was the most important line of defense in SC1204 against radiation. The next abundant protein was phosphoribosyl aminoimidazole carboxamide formyltransferase/IMP cyclohydrolase (AICAR Tfase/IMPCH), the key enzyme in the biosynthetic pathway of purine that is anti-radiation compound. Other proteins changing significantly (p < 0.05) after radiation exposure included urocanate hydratase, dihydrolipoyl dehydrogenase, succinyl-CoA synthetase subunit alpha, phosphoglycerate kinase, cell division protein FtsZ, elongation factor Ts and Tu, translation elongation factor Tu and G, 30S ribosomal protein S1, histidyl-tRNA synthetase, and arginyl-tRNA synthetase, which were considered to be the key proteins in urocanate metabolism, tricarboxylic acid cycle, glycolysis, cell division process, and synthesis process of proteins. Therefore, these proteins may also play important roles in radiation resistance in M. luteus.

The preparation of <100 particles per trial having the same mole fraction of 12 inorganic compounds at diameters of 6.8, 3.8, or 2.6 [mu]m followed by their deposition onto human lung cells (A549) with measurement of the relative downstream differential expression of ICAM-1

NASA Astrophysics Data System (ADS)

Eleghasim, Ndukauba M.; Haddrell, Allen E.; van Eeden, Stephen; Agnes, George R.

2006-12-01

The characterization of particulate matter suspended in the troposphere (PM10) based on size is an important basis for assessing the extent of their adverse effects on human health. The relevance of such assessments is anticipated to be significantly improved through the continued development of tools that can identify the chemical components within individual ambient particles, and the injury that they cause. We use recently reported methodology to create mimics of ambient particle types of known size and chemical composition that are levitated within an ac trap. The ac trap uses electric fields to levitate the particles that have a given mass and net elementary charge, and as such the ac trap is a mass-to-charge filter. The ac trap was used to levitate populations of particles where the size of particles in any given population could be altered. The levitated particles are delivered direct from the ac trap to human lung cells (A549), in vitro, with downstream measurement of differential expression of intercellular adhesion molecule (ICAM)-1 and counting of the number of particles actually delivered to the culture using an optical microscope. In this study, the chemical composition of the ambient particle mimics was restricted to inorganic compounds whose relative abundance was purposely designed to mimic the average abundance in Environmental Health Center-93 (EHC-93) particles. The sizes of the multilelement particle types prepared were 6.8 +/- 0.5, 3.8 +/- 0.3, 2.6 +/- 0.2 (mean +/- S.D.). Particles of either elemental carbon, or elemental carbon containing glycerol were used as control particle types. In any given experiment, a known number of particles, but always <100, of a given size, were deposited onto a small region of an A549 cell culture. Following an 18-h incubation period and anti-body labeling of ICAM-1, the fluorescence emission from a 1.07 mm2 area of the cell culture centered at the site of particle deposition was acquired. The relative

Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses

PubMed Central

Navarro-Sanchez, Erika; Altmeyer, Ralf; Amara, Ali; Schwartz, Olivier; Fieschi, Franck; Virelizier, Jean-Louis; Arenzana-Seisdedos, Fernando; Desprès, Philippe

2003-01-01

Dengue virus (DV) is a mosquito-borne flavivirus that causes haemorrhagic fever in humans. DV primarily targets immature dendritic cells (DCs) after a bite by an infected mosquito vector. Here, we analysed the interactions between DV and human-monocyte-derived DCs at the level of virus entry. We show that the DC-specific ICAM3-grabbing non-integrin (DC-SIGN) molecule, a cell-surface, mannose-specific, C-type lectin, binds mosquito-cell-derived DVs and allows viral replication. Conclusive evidence for the involvement of DC-SIGN in DV infection was obtained by the inhibition of viral infection by anti-DC-SIGN antibodies and by the soluble tetrameric ectodomain of DC-SIGN. Our data show that DC-SIGN functions as a DV-binding lectin by interacting with the DV envelope glycoprotein. Mosquito-cell-derived DVs may have differential infectivity for DC-SIGN-expressing cells. We suggest that the differential use of DC-SIGN by viral envelope glycoproteins may account for the immunopathogenesis of DVs. PMID:12783086

Low-Temperature Ionizing Radiation Resistance of Deinococcus radiodurans and Antarctic Dry Valley Bacteria

NASA Astrophysics Data System (ADS)

Dartnell, Lewis R.; Hunter, Stephanie J.; Lovell, Keith V.; Coates, Andrew J.; Ward, John M.

2010-09-01

The high flux of cosmic rays onto the unshielded surface of Mars poses a significant hazard to the survival of martian microbial life. Here, we determined the survival responses of several bacterial strains to ionizing radiation exposure while frozen at a low temperature characteristic of the martian near-subsurface. Novel psychrotolerant bacterial strains were isolated from the Antarctic Dry Valleys, an environmental analogue of the martian surface, and identified by 16S rRNA gene phylogeny as representatives of Brevundimonas, Rhodococcus, and Pseudomonas genera. These isolates, in addition to the known radioresistant extremophile Deinococcus radiodurans, were exposed to gamma rays while frozen on dry ice (-79°C). We found D. radiodurans to exhibit far greater radiation resistance when irradiated at -79°C than was observed in similar studies performed at higher temperatures. This greater radiation resistance has important implications for the estimation of potential survival times of microorganisms near the martian surface. Furthermore, the most radiation resistant of these Dry Valley isolates, Brevundimonas sp. MV.7, was found to show 99% 16S rRNA gene similarity to contaminant bacteria discovered in clean rooms at both Kennedy and Johnson Space Centers and so is of prime concern to efforts in the planetary protection of Mars from our lander probes. Results from this experimental irradiation, combined with previous radiation modeling, indicate that Brevundimonas sp. MV.7 emplaced only 30 cm deep in martian dust could survive the cosmic radiation for up to 100,000 years before suffering 106 population reduction.

Development of the radiation-resistant strain of Moraxella osloensis and effect of penicillin G on its growth

NASA Astrophysics Data System (ADS)

Lim, Sangyong; Yun, Hyejeong; Joe, Minho; Kim, Dongho

2009-07-01

A series of repeated exposures to γ-radiation with intervening outgrowth of survivors was used to develop radioresistant cultures of Moraxella osloensis that have been recognized as potential pathogenic microorganism. The D10 value of the radiation-resistant strain, 5.903±0.006 kGy, was increased by four-fold compared to the parent wild-type strain, 1.637±0.004 kGy. Since most strains of M. osloensis are sensitive to penicillin, we have surveyed the sensitivity of radiation-resistant strain to this antibiotic. When the optical density was monitored after the addition of penicillin G, the radioresistant strain appeared to be more resistant to only a low concentration of penicillin G (0.5 U/ml) than the parent strain. Interestingly, however, there was no apparent difference in the number of viable cells between both strains. Scanning electron microscope data showed that the resistance cells were generally larger than the parent cells, suggesting that this increase in size may cause a higher optical density of radioresistant cells. In conclusion, radiation mutation does not affect the penicillin resistance of M. osloensis.

Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1

PubMed Central

Xie, Fang; Li, Zhi-Ping; Wang, Hong-Wei; Fei, Xiang; Jiao, Zi-Yu; Tang, Wen-Bo; Tang, Jie; Luo, Yu-Kun

2016-01-01

Objective To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). Methods The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle’s maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. Results The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6–7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. Conclusion The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level. PMID:27120181

Designing Radiation Resistance in Materials for Fusion Energy

NASA Astrophysics Data System (ADS)

Zinkle, S. J.; Snead, L. L.

2014-07-01

Proposed fusion and advanced (Generation IV) fission energy systems require high-performance materials capable of satisfactory operation up to neutron damage levels approaching 200 atomic displacements per atom with large amounts of transmutant hydrogen and helium isotopes. After a brief overview of fusion reactor concepts and radiation effects phenomena in structural and functional (nonstructural) materials, three fundamental options for designing radiation resistance are outlined: Utilize matrix phases with inherent radiation tolerance, select materials in which vacancies are immobile at the design operating temperatures, or engineer materials with high sink densities for point defect recombination. Environmental and safety considerations impose several additional restrictions on potential materials systems, but reduced-activation ferritic/martensitic steels (including thermomechanically treated and oxide dispersion-strengthened options) and silicon carbide ceramic composites emerge as robust structural materials options. Materials modeling (including computational thermodynamics) and advanced manufacturing methods are poised to exert a major impact in the next ten years.

THE RESISTANCE TO $gamma$ RADIATION OF THE WORKER BEE (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Courtois, G.; Lecomte, J.

The worker bee which has been subjected to gamma radiation from a Co/ sup 60/ source can withstand without apparent physical damage a dose of 18,000 r. At 90,000 r there is, however, appreciable damage. At a dose of 200,000 r, death is immediate in 100% of the cases. The physiological state of the bee plays an important role in determining its resistance to gamma radiation. (auth)

Radiation resistance of lactobacilli isolated from radurized meat relative to growth and environment.

PubMed

Hastings, J W; Holzapfel, W H; Niemand, J G

1986-10-01

Of 113 lactobacilli isolated from radurized (5 kGy) minced meat, 7 Lactobacillus sake strains, 1 L. curvatus strain, and 1 L. farciminis strain were used for radiation resistance studies in a semisynthetic substrate (i.e., modified MRS broth). Five reference Lactobacillus spp., one Staphylococcus aureus strain, and one Salmonella typhimurium strain were used for comparative purposes. All L. sake isolates exhibited the phenomenon of being more resistant to gamma-irradiation in the exponential (log) phase than in the stationary phase of their growth cycles by a factor of 28%. Four references strains also exhibited this phenomenon, with L. sake (DSM 20017) showing a 68% increase in resistance in the log phase over the stationary phase. This phenomenon was not common to all bacteria tested and is not common to all strains with high radiation resistance. Four L. sake isolates and three reference strains were used in radiation sensitivity testing in a natural food system (i.e., meat). The bacteria were irradiated in minced meat and packaged under four different conditions (air, vacuum, CO2, and N2). Organisms exhibited the highest death rate (lowest D10 values [doses required to reduce the logarithm of the bacterial population by 1] ) under CO2 packaging conditions, but resistance to irradiation was increased under N2. The D10 values of the isolates were generally greater than those of the reference strains. The D10 values were also higher (approximately two times) in meat than in semisynthetic growth medium.

RADIATION-RESISTANT FIBER OPTIC STRAIN SENSORS FOR SNS TARGET INSTRUMENTATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blokland, Willem; Bryan, Jeff; Riemer, Bernie

2016-01-01

Measurement of stresses and strains in the mercury tar-get vessel of the Spallation Neutron Source (SNS) is important to understand the structural dynamics of the target. This work reports the development of radiation-resistant fiber optic strain sensors for the SNS target in-strumentation.

PROSPECTIVE EVALUATION OF AN IN VITRO RADIATION RESISTANCE ASSAY IN LOCALLY ADVANCED CANCER OF THE UTERINE CERVIX: A SOUTHWEST ONCOLOGY GROUP STUDY

PubMed Central

Randall, Leslie M; Monk, Bradley J; Moon, James; Parker, Ricardo; Al-Ghazi, Muthana; Wilczynski, Sharon; Fruehauf, John P; Markman, Maurie; Burger, Robert A

2010-01-01

Objectives To investigate the feasibility of performing a fresh-tissue, in vitro radiation resistance assay (IVRRA) in a cooperative group setting and to assess the association of IVRRA results with clinical outcomes. Methods Women with Stages IIB-IVA carcinoma of the uterine cervix without obvious para-aortic lymphadenopathy on imaging were eligible. Primary tumor biopsies were shipped to a central testing facility where agar-based cell suspensions were exposed to 300 cGy of RT ± cisplatin and cultured for 5 days. 3H-thymidine incorporation was used to determine percent cell inhibition (PCI) of test specimen compared to that of the untreated control. Tumors were considered to exhibit extreme radiation resistance (ERR), intermediate radiation resistance (IRR) or low radiation resistance (LRR) based on a standard data set from 39 previously studied specimens. Standardized doses of external beam radiation and intracavitary brachytherapy, when feasible, in addition to platinum-based chemotherapy were mandated. Progression-free survival (PFS) was the primary endpoint. Clinical response and overall survival (OS) were secondary endpoints. Clinical investigators were blinded to assay data and vice versa. Results Thirty-six patients were enrolled, but analysis was limited to 17 patients whose specimens were adequate for IVRRA. The median follow-up time was 40 months. There was no association between IVRRA and response. In the Cox model, IRR/ERR tumors showed worse PFS [HR=11.2 (95% CI 1.3–96, p=0.03)] and worse OS [HR=11.7 (95% CI 1.4–99.6, p=0.03)] compared to LRR tumors when IVRRA was performed with RT alone, but there were no associations between IVRRA and PFS or OS when cisplatin was added to the IVRRA. Conclusions IVRRA (RT alone) results correlated with PFS and OS in this prospective trial, but follow-up trials are indicated to address feasibility and to confirm results in an expanded cohort. If confirmed, IVRRA could potentially direct molecular identification

Radiation resistance and comparative performance of ITO/InP and n/p InP homojunction solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.; Hart, R. E., Jr.; Coutts, T. J.

1988-01-01

The radiation resistance of ITO/InP cells processed by dc magnetron sputtering is compared to that of standard n/p InP and GaAs homojunction cells. After 20 MeV proton irradiations, it is found that the radiation resistance of the present ITO/InP cell is comparable to that of the n/p homojunction InP cell and that both InP cell types have radiation resistances significantly greater than GaAs. The relatively lower radiation resistance, observed at higher fluence, for the InP cell with the deepest junction depth, is attributed to losses in the cells emitter region. Diode parameters obtained from I sub sc - V sub oc plots, data from surface Raman spectrosocpy, and determinations of surface conductivity type are used to investigate the configuration of the ITO/InP cells. It is concluded that these latter cells are n/p homojunctions, the n-region consisting of a disordered layer at the oxide semiconductor.

Radiation resistance and comparative performance of ITO/InP and n/p InP homojunction solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.; Hart, R. E., Jr.; Coutts, T. J.

1988-01-01

The radiation resistance of ITO/InP cells processed by DC magnetron sputtering is compared to that of standard n/p InP and GaAs homojunction cells. After 20 MeV proton irradiations, it is found that the radiation resistance of the present ITO/InP cell is comparable to that of the n/p homojunction InP cell and that both InP cell types have radiation resistance significantly greater than GaAs. The relatively lower radiation resistance, observed at higher fluence, for the InP cell with the deepest junction depth, is attributed to losses in the cells emitter region. Diode parameters obtained from I sub sc - V sub oc plots, data from surface Raman spectroscopy, and determinations of surface conductivity types are used to investigate the configuration of the ITO/InP cells. It is concluded that thesee latter cells are n/p homojunctions, the n-region consisting of a disordered layer at the oxide semiconductor.

Ionizing-radiation resistance in the desiccation-tolerant cyanobacterium Chroococcidiopsis

NASA Technical Reports Server (NTRS)

Billi, D.; Friedmann, E. I.; Hofer, K. G.; Caiola, M. G.; Ocampo-Friedmann, R.

2000-01-01

The effect of X-ray irradiation on cell survival, induction, and repair of DNA damage was studied by using 10 Chroococcidiopsis strains isolated from desert and hypersaline environments. After exposure to 2.5 kGy, the percentages of survival for the strains ranged from 80 to 35%. In the four most resistant strains, the levels of survival were reduced by 1 or 2 orders of magnitude after irradiation with 5 kGy; viable cells were recovered after exposure to 15 kGy but not after exposure to 20 kGy. The severe DNA damage evident after exposure to 2.5 kGy was repaired within 3 h, and the severe DNA damage evident after exposure to 5 kGy was repaired within 24 h. The increase in trichloroacetic acid-precipitable radioactivity in the culture supernatant after irradiation with 2.5 kGy might have been due to cell lysis and/or an excision process involved in DNA repair. The radiation resistance of Chroococcidiopsis strains may reflect the ability of these cyanobacteria to survive prolonged desiccation through efficient repair of the DNA damage that accumulates during dehydration.

ABC transporter activity linked to radiation resistance and molecular subtype in pediatric medulloblastoma

PubMed Central

2013-01-01

Background Resistance to radiation treatment remains a major clinical problem for patients with brain cancer. Medulloblastoma is the most common malignant brain tumor of childhood, and occurs in the cerebellum. Though radiation treatment has been critical in increasing survival rates in recent decades, the presence of resistant cells in a substantial number of medulloblastoma patients leads to relapse and death. Methods Using the established medulloblastoma cell lines UW228 and Daoy, we developed a novel model system to enrich for and study radiation tolerant cells early after radiation exposure. Using fluorescence-activated cell sorting, dead cells and cells that had initiated apoptosis were removed, allowing surviving cells to be investigated before extensive proliferation took place. Results Isolated surviving cells were tumorigenic in vivo and displayed elevated levels of ABCG2, an ABC transporter linked to stem cell behavior and drug resistance. Further investigation showed another family member, ABCA1, was also elevated in surviving cells in these lines, as well as in early passage cultures from pediatric medulloblastoma patients. We discovered that the multi-ABC transporter inhibitors verapamil and reserpine sensitized cells from particular patients to radiation, suggesting that ABC transporters have a functional role in cellular radiation protection. Additionally, verapamil had an intrinsic anti-proliferative effect, with transient exposure in vitro slowing subsequent in vivo tumor formation. When expression of key ABC transporter genes was assessed in medulloblastoma tissue from 34 patients, levels were frequently elevated compared with normal cerebellum. Analysis of microarray data from independent cohorts (n = 428 patients) showed expression of a number of ABC transporters to be strongly correlated with certain medulloblastoma subtypes, which in turn are associated with clinical outcome. Conclusions ABC transporter inhibitors are already being

Quantitative filter technique measurements of spectral light absorption by aquatic particles using a portable integrating cavity absorption meter (QFT-ICAM).

PubMed

Röttgers, Rüdiger; Doxaran, David; Dupouy, Cecile

2016-01-25

The accurate determination of light absorption coefficients of particles in water, especially in very oligotrophic oceanic areas, is still a challenging task. Concentrating aquatic particles on a glass fiber filter and using the Quantitative Filter Technique (QFT) is a common practice. Its routine application is limited by the necessary use of high performance spectrophotometers, distinct problems induced by the strong scattering of the filters and artifacts induced by freezing and storing samples. Measurements of the sample inside a large integrating sphere reduce scattering effects and direct field measurements avoid artifacts due to sample preservation. A small, portable, Integrating Cavity Absorption Meter setup (QFT-ICAM) is presented, that allows rapid measurements of a sample filter. The measurement technique takes into account artifacts due to chlorophyll-a fluorescence. The QFT-ICAM is shown to be highly comparable to similar measurements in laboratory spectrophotometers, in terms of accuracy, precision, and path length amplification effects. No spectral artifacts were observed when compared to measurement of samples in suspension, whereas freezing and storing of sample filters induced small losses of water-soluble pigments (probably phycoerythrins). Remaining problems in determining the particulate absorption coefficient with the QFT-ICAM are strong sample-to-sample variations of the path length amplification, as well as fluorescence by pigments that is emitted in a different spectral region than that of chlorophyll-a.

Degraded carrageenan causing colitis in rats induces TNF secretion and ICAM-1 upregulation in monocytes through NF-kappaB activation.

PubMed

Benard, Claudine; Cultrone, Antonietta; Michel, Catherine; Rosales, Carlos; Segain, Jean-Pierre; Lahaye, Marc; Galmiche, Jean-Paul; Cherbut, Christine; Blottière, Hervé M

2010-01-13

Carrageenan (CGN) is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN) can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1) to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2) to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule. Peripheral blood monocytes (PBM) and THP-1 monocytic cells were cultured in the presence of either 10 or 40 kDa, dCGN. The 40 kDa, but not the 10 kDa dCGN, induced colitis in in vivo. Degraded CGN inhibited THP-1 cell proliferation in vitro, arresting the cells in G1 phase. In addition, dCGN increased ICAM-1 expression in both PBM and THP-1 cells with a major effect seen after 40 kDa dCGN exposure. Also, dCGN stimulated monocyte aggregation in vitro that was prevented by incubation with anti-ICAM-1 antibody. Finally, dCGN stimulated TNF-alpha expression and secretion by both PBM and THP-1 cells. All these effects were linked to NF-kappaB activation. These data strongly suggest that the degraded forms of CGN have a pronounced effect on monocytes, characteristic of an inflammatory phenotype.

Comparative radiation resistance, temperature dependence and performance of diffused junction indium phosphide solar cells

NASA Technical Reports Server (NTRS)

Weinberg, I.; Swartz, C. K.; Hart, R. E., Jr.; Ghandhi, S. K.; Borrego, J. M.

1987-01-01

Indium phosphide solar cells whose p-n junctions were processed by the open tube capped diffusion and by the closed tube uncapped diffusion of sulfur into Czochralski-grown p-type substrates are compared. Differences found in radiation resistance were attributed to the effects of increased base dopant concentration. Both sets of cells showed superior radiation resistance to that of gallium arsenide cells, in agreement with previous results. No correlation was, however, found between the open-circuit voltage and the temperature dependence of the maximum power.

Radiation resistance of asporogenous bacteria in frozen beef. Final report, Sep 1974--Feb 1975

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maxcy, R.B.; Rowley, D.B.; Annellis, A.

1976-03-01

A scheme was developed to isolate the most radiation resistant vegetative microbial cells occurring in beef. Selection of pure cultures and enrichment provided 16 apparently different isolates with higher radiation resistance than spores of Clostridium botulinum. Most of these bacteria were found to be Moraxella or Acinetobacter. They grew over a temperature range of 2 - 50 C. Preliminary data indicated the isolates to be relatively sensitive to heat and to limited oxygen. It would appear these organisms are rather widespread and frequent in nature. (GRA)

Increase of radiation resistance of a soil microflora exposed to long-term gamma irradiation. [/sup 60/Co

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eriksen, W.H.; Emborg, C.

1978-10-01

Soil microflora were exposed to long-term (18 months) gamma irradiation in an open-air facility at three different doses, 15, 150, and 1500 krads/18 months. The radiation resistance increased at all doses when compared with the radiation resistance of the microflora from soil shielded from the irradiation with a lead wall.

Evaluation of Radiation Response and Gold Nanoparticle Enhancement in Drug-Resistant Pancreatic Cancer Cells

NASA Astrophysics Data System (ADS)

Abourabia, Assya

Pancreatic cancer is a major cause of cancer-related death worldwide after lung cancer and colorectal cancer Pancreatic treatment modalities consist of surgery, chemotherapy, and radiation therapy or combination of these therapies. These modalities are good to some extents but they do have some limitations. For example, during the chemotherapy, tumor cells can develop some escape mechanisms and become chemoresistant to protect themselves against the chemo drugs and pass on theses escape mechanisms to their offspring, despite the treatment given. Cancer Cells can become chemoresistant by many mechanisms, for example, decreased drug influx mechanisms, decreased of drug transport molecules, decreased drug activation, altered drug metabolism that diminishes the capacity of cytotoxic drugs, and enhanced repair of DNA damage. Given that some of these chemoresistance mechanisms may impact sensitivity to radiation. Therefore, there is a strong need for a new alternative treatment option to amplify the therapeutic efficacy of radiotherapy and eventually increase the overall efficacy of cancer treatment. Nano-radiation therapy is an emerging and promising modality aims to enhance the therapeutic efficacy of radiotherapy through the use of radiosensitizing nanoparticles. The primary goal of using GNP-enhanced radiation is that GNPs are potent radiosensitizer agents that sensitize the tumor cells to radiation, and these agents promote generation of the free radicals produced by Photo- and Auger- electrons emission at the molecular level which can enhance the effectiveness of radiation-induced cancer cell death. The main aim of this research is to analyze and compare the response to radiation of pancreatic cancer cells, PANC-1, and PANC-1 cells that are resistant to oxaliplatin, PANC-1/OR, and investigate the radiation dose enhancement effect attributable to GNP when irradiating the cells with low-energy (220 kVp) beam at various doses. Based on evidence from the existing

Characterization of Radiation-Resistant Vegetative Bacteria in Beef1

PubMed Central

Welch, Ardyce B.; Maxcy, R. B.

1975-01-01

Ground beef contains numerous microorganisms of various types. The commonly recognized bacteria are associated with current problems of spoilage. Irradiation, however, contributes a new factor through selective destruction of the microflora. The residual microorganisms surviving a nonsterilizing dose are predominantly gram-negative coccobacilli. Various classifications have been given, e.g., Moraxella, Acinetobacter, Achromobacter, etc. For a more detailed study of these radiation-resistant bacteria occurring in ground beef, an enrichment procedure was used for isolation. By means of morphological and biochemical tests, most of the isolates were found to be Moraxella, based on current classifications. The range of growth temperatures was from 2 to 50 C. These bacteria were relatively heat sensitive, e.g., D10 of 5.4 min at 70 C or less. The radiation resistance ranged from D10 values of 273 to 2,039 krad. Thus, some were more resistant than any presently recognized spores. A reference culture of Moraxella osloensis was irradiated under conditions comparable to the enrichment procedure used with the ground beef. The only apparent changes were in morphology and penicillin sensitivity. However, after a few subcultures these bacteria reverted to the characteristics of the parent strain. Thus, it is apparent that these isolates are a part of the normal flora of ground beef and not aberrant forms arising from the irradiation procedure. The significance, if any, of these bacteria is not presently recognized. Images PMID:1164011

[Circulating levels of MCP-1, VEGF-A, sICAM-1, sVCAM-1, sE-selectin and sVE-cadherin: Relationship with components of metabolic syndrome in young population].

PubMed

Guzmán-Guzmán, Iris Paola; Zaragoza-García, Oscar; Vences-Velázquez, Amalia; Castro-Alarcón, Natividad; Muñoz-Valle, José Francisco; Parra-Rojas, Isela

2016-11-18

Inflammation and endothelial dysfunction are considered the primary manifestations of the cardiovascular disease. Studies have established a relationship among components of metabolic syndrome (MetS) with inflammatory markers and the loss of permeability, vasoconstriction and vasodilatation endothelial. To determine the relationship among the concentrations of soluble endothelial dysfunction molecules and inflammation cytokines and components of the metabolic syndrome in young population. A study was performed in 240 young adult students ages 18-28 years. To define the presence of clinical and metabolic alterations and MetS the modified ATP-III criteria was considered. In all subjects were determined sociodemographic characteristics, anthropometric measures and the metabolic profile. Circulating levels of MCP-1, VEGF-A, sICAM-1, sVCAM-1, sE-selectin and sVE-cadherin were determined by ELISA immunoassay (Bioscience). Statistical analysis was performed using STATA statistical software v. 9.2. From all the participants, 44.6% had obesity, 59.9% had abdominal obesity, 49.6% low HDL-c and 16.7% high levels triglycerids. The 16.25% of the population showed 3 or more components of the MetS. Elevated MCP-1, sICAM-1 and sE-selectin levels were linked to the presence of obesity. In a model adjusted by age-gender, high soluble levels of MCP-1 and VEGF-A were linked with abdominal obesity (OR=1.83; 1.02-3.28 and OR=2.03; 1.15-3.56, respectively), as well as to the presence of the 2 components of MetS. sVCAM-1 levels were associated with impaired glucose (OR=4.74; 1.32-17.0); sE-selectin with low HDL-c (OR=1.99; 1.05-3.75), although sICAM-1 and sVE-cadherin were associated with impaired systolic blood pressure (OR=4.04; 1.24-13.1 and OR=6.28; 1.90-20.7, respectively). Levels of circulating MCP-1 and VEGF-A were associated with adiposity, levels of sVCAM-1 with the presence of impaired glucose, sE-selectin with low HDL-c, while the levels of sICAM-1 and sVE-cadherin were

Radiation resistance of lactobacilli isolated from radurized meat relative to growth and environment.

PubMed Central

Hastings, J W; Holzapfel, W H; Niemand, J G

1986-01-01

Of 113 lactobacilli isolated from radurized (5 kGy) minced meat, 7 Lactobacillus sake strains, 1 L. curvatus strain, and 1 L. farciminis strain were used for radiation resistance studies in a semisynthetic substrate (i.e., modified MRS broth). Five reference Lactobacillus spp., one Staphylococcus aureus strain, and one Salmonella typhimurium strain were used for comparative purposes. All L. sake isolates exhibited the phenomenon of being more resistant to gamma-irradiation in the exponential (log) phase than in the stationary phase of their growth cycles by a factor of 28%. Four references strains also exhibited this phenomenon, with L. sake (DSM 20017) showing a 68% increase in resistance in the log phase over the stationary phase. This phenomenon was not common to all bacteria tested and is not common to all strains with high radiation resistance. Four L. sake isolates and three reference strains were used in radiation sensitivity testing in a natural food system (i.e., meat). The bacteria were irradiated in minced meat and packaged under four different conditions (air, vacuum, CO2, and N2). Organisms exhibited the highest death rate (lowest D10 values [doses required to reduce the logarithm of the bacterial population by 1] ) under CO2 packaging conditions, but resistance to irradiation was increased under N2. The D10 values of the isolates were generally greater than those of the reference strains. The D10 values were also higher (approximately two times) in meat than in semisynthetic growth medium. PMID:3096207

DESIGN STUDY OF 20 T, 15 CM BORE HYBRID MAGNET WITH RADIATION RESISTANT INSERT FOR PION CAPTURE.

DOE Office of Scientific and Technical Information (OSTI.GOV)

WEGGEL,R.J.; PEARSON,C.E.; KING,B.J.

2001-06-18

To capture pions the Neutrino Factory and Muon Collider Collaboration needs a field of {approx}20 T throughout a cylinder 15 cm in diameter and 60 cm long, falling over the next 18 m to 1.25 T, while the bore increases fourfold inversely as the square root of the field. We propose a hybrid system. The superconducting magnet is of world-class parameters, storing 600 MJ and including a coil to generate 14 T in a bore of {approx}1.3 m. Intercoil forces reach 100 MN. For high radiation resistance, the insert coil is of mineral-insulated hollow conductor, as developed for the Japanmore » Hadron Facility; it would require 12 MW to generate 6 T. Needed is research to develop a more efficient hollow conductor or radiation-resistant insulator for a Bitter coil.« less

Thermal ripples in a resistive and radiative instability. [in solar corona

NASA Technical Reports Server (NTRS)

Steinolfson, R. S.

1984-01-01

The development of the resistive tearing instability in the case of sheared magnetic fields is considered, taking into account also the occurrence of a radiatively driven thermal instability. It is pointed out that thermal conduction has generally been neglected in theories similar to those discussed. The present investigation is concerned with a consideration of both parallel and perpendicular thermal conduction, in addition to finite resistivity and radiative loss. Attention is given to the equations and the model, the spatial singularity which arises with consideration of only the parallel heat conduction, the removal of this singularity and the formation of temperature oscillations (thermal ripples) by inclusion of the perpendicular heat-flux component, and details regarding the numerical procedure. A brief explanation is provided of the conditions required for the oscillations, and potential implications of the results with respect to the solar flare are discussed.

Theory of the high base resistivity n(+)pp(+) silicon solar cell and its application to radiation damage effects

NASA Technical Reports Server (NTRS)

Goradia, C.; Weinberg, I.

1985-01-01

Particulate radiation in space is a principal source of silicon solar cell degradation, and an investigation of cell radiation damage at higher base resistivities appears to have implication toward increasing solar cell and, therefore, useful satellite lifetimes in the space environment. However, contrary to expectations, it has been found that for cells with resistivities of 84 and 1250 ohm cm, the radiation resistance decreases as cell base resistivity increases. An analytical solar-cell computer model was developed with the objective to determine the reasons for this unexpected behavior. The present paper has the aim to describe the analytical model and its use in interpreting the behavior, under irradiation, of high-resistivity solar cells. Attention is given to boundary conditions at the space-charge region edges, cell currents, cell voltages, the generation of the theoretical I-V characteristic, experimental results, and computer calculations.

Assessment of Gamma Radiation Resistance of Spores Isolated from the Spacecraft Assembly Facility During MSL Assembly

NASA Technical Reports Server (NTRS)

Chopra, Arsh; Ramirez, Gustavo A.; Venkateswaran, Kasthuri J.; Vaishampayan, Parag A.

2011-01-01

Spore forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate extreme environmental conditions such as radiation, desiccation, and high temperatures. Since the Viking era (early 1970's), spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. There is a growing concern that desiccation and extreme radiation resistant spore forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequently proliferate on another solar body. Such forward contamination would certainly jeopardize future life detection or sample return technologies. It is important to recognize that different classes of organisms are critical while calculating the probability of contamination, and methods must be devised to estimate their abundances. Microorganisms can be categorized based on radiation sensitivity as Type A, B, C, and D. Type C represents spores resistant to radiation (10% or greater survival above 0.8 mRad gamma radiation). To address these questions we have purified 96 spore formers, isolated during planetary protection efforts of Mars Science Laboratory assembly for gamma radiation resistance. The spores purified and stored will be used to generate data that can be used further to model and predict the probability of forward contamination.

Assessment of Gamma Radiation Resistance of Spores Isolated from the Spacecraft Assembly Facility During MSL Assembly

NASA Technical Reports Server (NTRS)

Chopra, Arsh; Ramirez, Gustavo A.; Vaishampayan, Parag A.; Venkateswaran, Kasthuri J.

2011-01-01

Spore forming bacteria, a common inhabitant of spacecraft assembly facilities, are known to tolerate extreme environmental conditions such as radiation, desiccation, and high temperatures. Since the Viking era (early 1970's), spores have been utilized to assess the degree and level of microbiological contamination on spacecraft and their associated spacecraft assembly facilities. There is a growing concern that desiccation and extreme radiation resistant spore forming microorganisms associated with spacecraft surfaces can withstand space environmental conditions and subsequently proliferate on another solar body. Such forward contamination would certainly jeopardize future life detection or sample return technologies. It is important to recognize that different classes of organisms are critical while calculating the probability of contamination, and methods must be devised to estimate their abundances. Microorganisms can be categorized based on radiation sensitivity as Type A, B, C, and D. Type C represents spores resistant to radiation (10% or greater survival above 0.8 Mrad gamma radiation). To address these questions we have purified 96 spore formers, isolated during planetary protection efforts of Mars Science Laboratory assembly for gamma radiation resistance. The spores purified and stored will be used to generate data that can be used further to model and predict the probability of forward contamination.

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

PubMed

Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

2014-12-24

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

Largazole, a class I histone deacetylase inhibitor, enhances TNF-α-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Salahuddin, E-mail: Salah.Ahmed@utoledo.edu; Riegsecker, Sharayah; Beamer, Maria

In the present study, we evaluated the effect of largazole (LAR), a marine-derived class I HDAC inhibitor, on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) activity. LAR (1–5 μM) had no adverse effect on the viability of RA synovial fibroblasts. Among the different class I HDACs screened, LAR (0.5–5 μM) inhibited the constitutive expression of HDAC1 (0–30%). Surprisingly, LAR increased class II HDAC [HDAC6] by ∼ 220% with a concomitant decrease in HDAC5 [30–58%] expression in RA synovial fibroblasts. SAHA (5 μM), a pan-HDAC inhibitor, also inducedmore » HDAC6 expression in RA synovial fibroblasts. Pretreatment of RA synovial fibroblasts with LAR further enhanced TNF-α-induced ICAM-1 and VCAM-1 expression. However, LAR inhibited TNF-α-induced MMP-2 activity in RA synovial fibroblasts by 35% when compared to the TNF-α-treated group. Further, the addition of HDAC6 specific inhibitor Tubastatin A with LAR suppressed TNF-α + LAR-induced ICAM-1 and VCAM-1 expression and completely blocked MMP-2 activity, suggesting a role of HDAC6 in LAR-induced ICAM-1 and VCAM-1 expression. LAR also enhanced TNF-α-induced phospho-p38 and phospho-AKT expression, but inhibited the expression of phospho-JNK and nuclear translocation of NF-κBp65 in RA synovial fibroblasts. These results suggest that LAR activates p38 and Akt pathways and influences class II HDACs, in particular HDAC6, to enhance some of the detrimental effects of TNF-α in RA synovial fibroblasts. Understanding the exact role of different HDAC isoenzymes in RA pathogenesis is extremely important in order to develop highly effective HDAC inhibitors for the treatment of RA. - Highlights: • Largazole enhances TNF-α-induced ICAM-1 and VCAM-1. • Largazole upregulates class II HDAC (HDAC6) in RA synovial fibroblasts. • Largazole also induces the expression of

A distinct profile of serum levels of soluble intercellular adhesion molecule-1 and intercellular adhesion molecule-3 in mycosis fungoides and Sézary syndrome.

PubMed

López-Lerma, Ingrid; Estrach, Maria Teresa

2009-08-01

Cell adhesion molecules (CAMs) play a pivotal role in cutaneous localization of T cells. Tissue-selective localization of T lymphocytes to the skin is crucial for immune surveillance and in the pathogenesis of skin disorders. To detect the profile of soluble CAMs in patients with cutaneous T-cell lymphoma (CTCL), we investigated the levels of intercellular adhesion molecule-1 (ICAM-1, soluble ICAM-1 [sICAM-1]); intercellular adhesion molecule-3 (sICAM-3); vascular cell adhesion molecule-1 (sVCAM-1); and E-selectin (sE-selectin) in sera from patients with T-cell-mediated skin diseases. Serum levels of the 4 CAMs were measured by enzyme-linked immunosorbent assay in 42 participants including 11 patients with early stages of CTCL; 7 with advanced stages of CTCL including Sézary syndrome; 12 with inflammatory skin diseases (psoriasis and atopic dermatitis); 8 with skin diseases that may evolve into CTCL; and healthy individuals. Levels were correlated with biological parameters known as prognostic factors in non-Hodgkin lymphomas. In patients with CTCL, significantly increased levels of sICAM-1 and sICAM-3 were found when compared with healthy individuals and patients with inflammatory dermatosis. Soluble E-selectin and sVCAM-1 levels were not increased. There were significant positive correlations between sICAM-1 and sICAM-3 levels and each of them with beta2-microglobulin levels. Limited number of patients was a limitation. There is a distinct profile of soluble CAMs in patients with CTCL. However, future studies with a larger group of patients are needed to confirm these findings. We propose that high sICAM-1 and sICAM-3 levels have important implications in the context of immune response and immune surveillance in these patients.

Manganese supplementation increases adiponectin and lowers ICAM-1 and creatinine blood levels in Zucker type 2 diabetic rats, and downregulates ICAM-1 by upregulating adiponectin multimerization protein (DsbA-L) in endothelial cells.

PubMed

Burlet, Elodie; Jain, Sushil K

2017-05-01

Blood and tissue levels of manganese (Mn) are lower in type 2 diabetic and atherosclerosis patients compared with healthy subjects. Adiponectin has anti-diabetic and anti-atherogenic properties. Impairment in Disulfide bond A-like protein (DsbA-L) is associated with low adiponectin levels and diabetes. This study investigates the hypothesis that the beneficial effects of Mn supplementation are mediated by adiponectin and DsbA-L. At 6 weeks of age, Male Zucker diabetic fatty rats (ZDF) were randomly divided into two groups: diabetic controls and Mn-supplemented diabetic rats. Each rat was supplemented with Mn (D+Mn, 16 mg/kg BW) or water (placebo, D+P) daily for 7 weeks by oral gavage. For cell culture studies, Human Umbilical Vein Endothelial Cells (HUVEC) or 3T3L1 adipocytes were pretreated with Mn (0-10 µM MnCl 2 ) for 24 h, followed by high glucose (HG, 25 mM) or normal glucose (5 mM) exposure for another 24 h. Mn supplementation resulted in higher adiponectin (p = 0.01), and lower ICAM-1 (p = 0.04) and lower creatinine (p = 0.04) blood levels compared to those in control ZDF rats. Mn-supplemented rats also caused reduced oxidative stress (ROS) and NADPH oxidase, and higher DsbA-L expression in the liver (p = 0.03) of ZDF rats compared to those in livers of control rats; however, Fe levels in liver were lower but not significant (p = 0.08). Similarly, treatment with high glucose (25 mM) caused a decrease in DsbA-L, which was prevented by Mn supplementation in HUVEC and adipocytes. Mechanistic studies with DsbA-L siRNA showed that the beneficial effects of Mn supplementation on ROS, NOX4, and ICAM-1 expression were abolished in DsbA-L knock-down HUVEC. These studies demonstrate that DsbA-L-linked adiponectin mediates the beneficial effects observed with Mn supplementation and provides evidence for a novel mechanism by which Mn supplementation can increase adiponectin and reduce the biomarkers of endothelial dysfunction in diabetes.

Radiation resistant polypropylene blended with mobilizer,. antioxidants and nucleating agent

NASA Astrophysics Data System (ADS)

Shamshad, A.; Basfar, A. A.

2000-03-01

Post-irradiation storage of medical disposables prepared from isotactic polypropylene renders them brittle due to degradation. To avoid this, isotactic polypropylene [(is)PP] was blended with a mobilizer, dioctyl pthallate (DOP), three antioxidants (hindered amines and a secondary antioxidant) and benzoic acid to obtain radiation-resistant, thermally-stable and transparent material. Different formulations prepared were subjected to gamma radiation to doses of 25 and 50 kGy. Tests of breakage on bending after ageing in an oven at 70°C up to 12 months have shown that the addition of DOP and the antioxidants imparts improved radiation and thermal stability as compared to (is)PP alone or its blend with DOP. All the formulations irradiated or otherwise demonstrated excellent colour stability even after accelerated ageing at 70°C for prolonged periods.

Role of elevated plasma soluble ICAM-1 and bronchial lavage fluid IL-8 levels as markers of chronic lung disease in premature infants.

PubMed Central

Little, S.; Dean, T.; Bevin, S.; Hall, M.; Ashton, M.; Church, M.; Warner, J.; Shute, J.

1995-01-01

BACKGROUND--Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated. METHODS--Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers. RESULTS--Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV. CONCLUSIONS--The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease. PMID:7491556

Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma.

PubMed

Cook, Peter J; Thomas, Rozario; Kingsley, Philip J; Shimizu, Fumiko; Montrose, David C; Marnett, Lawrence J; Tabar, Viviane S; Dannenberg, Andrew J; Benezra, Robert

2016-10-01

In glioblastoma (GBM), Id1 serves as a functional marker for self-renewing cancer stem-like cells. We investigated the mechanism by which cyclooxygenase-2 (Cox-2)-derived prostaglandin E2 (PGE2) induces Id1 and increases GBM self-renewal and radiation resistance. Mouse and human GBM cells were stimulated with dimethyl-PGE2 (dmPGE2), a stabilized form of PGE2, to test for Id1 induction. To elucidate the signal transduction pathway governing the increase in Id1, a combination of short interfering RNA knockdown and small molecule inhibitors and activators of PGE2 signaling were used. Western blotting, quantitative real-time (qRT)-PCR, and chromatin immunoprecipitation assays were employed. Sphere formation and radiation resistance were measured in cultured primary cells. Immunohistochemical analyses were carried out to evaluate the Cox-2-Id1 axis in experimental GBM. In GBM cells, dmPGE2 stimulates the EP4 receptor leading to activation of ERK1/2 MAPK. This leads, in turn, to upregulation of the early growth response1 (Egr1) transcription factor and enhanced Id1 expression. Activation of this pathway increases self-renewal capacity and resistance to radiation-induced DNA damage, which are dependent on Id1. In GBM, Cox-2-derived PGE2 induces Id1 via EP4-dependent activation of MAPK signaling and the Egr1 transcription factor. PGE2-mediated induction of Id1 is required for optimal tumor cell self-renewal and radiation resistance. Collectively, these findings identify Id1 as a key mediator of PGE2-dependent modulation of radiation response and lend insight into the mechanisms underlying radiation resistance in GBM patients. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of Tumor Necrosis Factor α (TNF-α) and Interleukina 10 (IL-10) on Intercellular Cell Adhesion Molecule-1 (ICAM-1) and Cluster of Differentiation 31 (CD31) in Human Coronary Artery Endothelial Cells.

PubMed

Xue, Mingming; Qiqige, Chaolumen; Zhang, Qi; Zhao, Haixia; Su, Liping; Sun, Peng; Zhao, Pengwei

2018-06-27

BACKGROUND The aim of this study was to investigate the effects of TNF-α and IL-10 on the expression of ICAM-1 and CD31 in human coronary artery endothelial cells (HCAEC). MATERIAL AND METHODS HCAEC was treated with 0, 2.5 μg/l, 5 μg/l, and 10 μg/l of TNF-α for 2 h, 6 h, and 10 h, and with 0 μg/l, 10 μg/l, 100 μg/l, and 200 μg/l of IL-10 for 5 h, 10 h and 15 h, respectively. RNA inference of TNF-αR was performed with siRNA. Real-time PCR, Western blot analysis, and ELSA were used to detect the mRNA level and protein level of ICAM-1 and CD31. RESULTS TNF-α significantly increased the mRNA and protein expression of ICAM-1 (P<0.05), and 2.5 μg/l TNF-α had the most obvious effect. RNAi of TNF-aR reduced the induction of TNF-α on the mRNA and protein expression of ICAM-1 (P<0.05). TNF-α significantly decreased the CD31 in the supernatant (P<0.05), and 2.5 μg/l TNF-a had the most obvious effect. IL-10 significantly decreased the ICAM-1 protein level. IL-10 decreased the mRNA expression and the protein expression of CD31. The effect on mRNA was not significant (P>0.05), while the effect on the protein expression was significant (P<0.05). CONCLUSIONS TNF-α and IL-10 treatment can affect the expression of ICAM-1 and CD31 in HCAEC.

Antioxidant betalains from cactus pear (Opuntia ficus-indica) inhibit endothelial ICAM-1 expression.

PubMed

Gentile, C; Tesoriere, L; Allegra, M; Livrea, M A; D'Alessio, P

2004-12-01

It has been suggested that some pigments would have antioxidant properties and that their presence in dietary constituents would contribute to reduce the risk of oxidative stress-correlated diseases. Among others, inflammatory response depends on redox status and may implicate oxidative stress. Vascular endothelial cells are a direct target of oxidative stress in inflammation. We have tested the impact of the free radical scavenger and antioxidant properties of betalains from the prickle pear in an in vitro model of endothelial cells. Here we show the capacity of betalains to protect endothelium from cytokine-induced redox state alteration, through ICAM-1 inhibition.

Effects of endurance and high intensity training on ICAM-1 and VCAM-1 levels and arterial pressure in obese and normal weight adolescents.

PubMed

Kargarfard, Mehdi; Lam, Eddie T C; Shariat, Ardalan; Asle Mohammadi, Mahmoud; Afrasiabi, Saleh; Shaw, Ina; Shaw, Brandon S

2016-09-01

Obesity prevalence has increased in Iranian adolescents in recent years. However, few studies have examined the impact of intervention programs on this health issue. The main objective of this study was to evaluate the effects of 8-week endurance training (ET) and high intensity interval training (HIIT) on intercellular adhesion molecule-1(ICAM-1) and vascular adhesion molecule-1(VCAM-1) levels among obese and normal-weight male adolescents. Thirty obese and 30 normal-weight subjects were assigned to the ET, HIIT, or control group for eight weeks. Before and after the intervention, ICAM-1, VCAM-1, body weight, BMI, VO2max, and blood pressures were measured. SPSS (Version 21) was used for data analysis, and the significance level was set at p < 0.05. Mixed design ANOVAs indicated that the obese participants had significantly (p < 0.05) lower ICAM-1 levels in the ET (from 509 ± 61 ng/ml to 387 ± 43 ng/ml) and HIIT (from 517 ± 72 ng/ml to 374 ± 50 ng/ml), but their VCAM-1 level was significantly (p < 0.05) reduced only after the HIIT (from 1689 ± 119 ng/ml to 1282 ± 63 ng/ml). Similarly, normal weight participants significantly (p < 0.05) lowered their ICAM-1 levels in the ET (from 296 ± 18 ng/ml to 216 ± 14 ng/ml) and HIIT (from 289 ± 22 ng/ml to 202 ± 12 ng/ml), but their VCAM-1 level was significantly (p < 0.05) reduced only after the HIIT (from 895 ± 50 ng/ml to 673 ± 142 ng/ml). Systolic blood pressure and diastolic blood pressures of all the participants were significantly (p < 0.01) decreased at the conclusion of the ET and HIIT. While both the ET and HIIT were useful in lowering the SBP and DBP of the participants, HIIT was more effective than ET in reducing ICAM-1 and VCAM-1 content in normal and obese adolescents.

Physiologic Determinants of Radiation Resistance in Deinococcus radiodurans

PubMed Central

Venkateswaran, Amudhan; McFarlan, Sara C.; Ghosal, Debabrota; Minton, Kenneth W.; Vasilenko, Alexander; Makarova, Kira; Wackett, Lawrence P.; Daly, Michael J.

2000-01-01

Immense volumes of radioactive wastes, which were generated during nuclear weapons production, were disposed of directly in the ground during the Cold War, a period when national security priorities often surmounted concerns over the environment. The bacterium Deinococcus radiodurans is the most radiation-resistant organism known and is currently being engineered for remediation of the toxic metal and organic components of these environmental wastes. Understanding the biotic potential of D. radiodurans and its global physiological integrity in nutritionally restricted radioactive environments is important in development of this organism for in situ bioremediation. We have previously shown that D. radiodurans can grow on rich medium in the presence of continuous radiation (6,000 rads/h) without lethality. In this study we developed a chemically defined minimal medium that can be used to analyze growth of this organism in the presence and in the absence of continuous radiation; whereas cell growth was not affected in the absence of radiation, cells did not grow and were killed in the presence of continuous radiation. Under nutrient-limiting conditions, DNA repair was found to be limited by the metabolic capabilities of D. radiodurans and not by any nutritionally induced defect in genetic repair. The results of our growth studies and analysis of the complete D. radiodurans genomic sequence support the hypothesis that there are several defects in D. radiodurans global metabolic regulation that limit carbon, nitrogen, and DNA metabolism. We identified key nutritional constituents that restore growth of D. radiodurans in nutritionally limiting radioactive environments. PMID:10831446

Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.

PubMed

Huang, Wen-Chung; Dai, Yi-Wen; Peng, Hui-Ling; Kang, Chiao-Wei; Kuo, Chun-Yu; Liou, Chian-Jiun

2015-07-01

Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes. Copyright © 2015 Elsevier B.V. All rights reserved.

Radiation induces premature chromatid separation via the miR-142-3p/Bod1 pathway in carcinoma cells.

PubMed

Pan, Dong; Du, Yarong; Ren, Zhenxin; Chen, Yaxiong; Li, Xiaoman; Wang, Jufang; Hu, Burong

2016-09-13

Radiation-induced genomic instability plays a vital role in carcinogenesis. Bod1 is required for proper chromosome biorientation, and Bod1 depletion increases premature chromatid separation. MiR-142-3p influences cell cycle progression and inhibits proliferation and invasion in cervical carcinoma cells. We found that radiation induced premature chromatid separation and altered miR-142-3p and Bod1 expression in 786-O and A549 cells. Overexpression of miR-142-3p increased premature chromatid separation and G2/M cell cycle arrest in 786-O cells by suppressing Bod1 expression. We also found that either overexpression of miR-142-3p or knockdown of Bod1 sensitized 786-O and A549 cells to X-ray radiation. Overexpression of Bod1 inhibited radiation- and miR-142-3p-induced premature chromatid separation and increased resistance to radiation in 786-O and A549 cells. Taken together, these results suggest that radiation alters miR-142-3p and Bod1 expression in carcinoma cells, and thus contributes to early stages of radiation-induced genomic instability. Combining ionizing radiation with epigenetic regulation may help improve cancer therapies.

Acquired Tumor Cell Radiation Resistance at the Treatment Site Is Mediated Through Radiation-Orchestrated Intercellular Communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aravindan, Natarajan, E-mail: naravind@ouhsc.edu; Aravindan, Sheeja; Pandian, Vijayabaskar

2014-03-01

Purpose: Radiation resistance induced in cancer cells that survive after radiation therapy (RT) could be associated with increased radiation protection, limiting the therapeutic benefit of radiation. Herein we investigated the sequential mechanistic molecular orchestration involved in radiation-induced radiation protection in tumor cells. Results: Radiation, both in the low-dose irradiation (LDIR) range (10, 50, or 100 cGy) or at a higher, challenge dose IR (CDIR), 4 Gy, induced dose-dependent and sustained NFκB-DNA binding activity. However, a robust and consistent increase was seen in CDIR-induced NFκB activity, decreased DNA fragmentation, apoptosis, and cytotoxicity and attenuation of CDIR-inhibited clonal expansion when the cellsmore » were primed with LDIR prior to challenge dose. Furthermore, NFκB manipulation studies with small interfering RNA (siRNA) silencing or p50/p65 overexpression unveiled the influence of LDIR-activated NFκB in regulating CDIR-induced DNA fragmentation and apoptosis. LDIR significantly increased the transactivation/translation of the radiation-responsive factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), cMYC, and SOD2. Coculture experiments exhibit LDIR-influenced radiation protection and increases in cellular expression, secretion, and activation of radiation-responsive molecules in bystander cells. Individual gene-silencing approach with siRNAs coupled with coculture studies showed the influence of LDIR-modulated TNF-α, IL-1α, cMYC, and SOD2 in induced radiation protection in bystander cells. NFκB inhibition/overexpression studies coupled with coculture experiments demonstrated that TNF-α, IL-1α, cMYC, and SOD2 are selectively regulated by LDIR-induced NFκB. Conclusions: Together, these data strongly suggest that scattered LDIR-induced NFκB-dependent TNF-α, IL-1α, cMYC, and SOD2 mediate radiation protection to the subsequent challenge dose in tumor cells.« less

Assessment of Resistance of Bacillus Horneckiae Endospores to UV Radiation and Function of Their Extraneous Layer in Resistance

NASA Technical Reports Server (NTRS)

Zachariah, Malcolm M.; Vaishampayan, Parag

2011-01-01

Spore-forming microbes are highly resistant to various physical and chemical conditions, which include ionizing and UV radiation, desiccation and oxidative stress, and the harsh environment of outer space or planetary surfaces. The spore's resistance might be due to their metabolically dormant state, and/or by the presence of a series of protective structures that encase the interior-most compartment, the core, which houses the spore chromosome. These spores have multiple layers surrounding the cell that are not found in vegetative cells, and some species have an outer layer of proteins and glycoproteins termed the "exosporium" or a fibrous "extraneous layer" (EL). Bacillus horneckiae is an EL-producing novel sporeformer isolated from a Phoenix spacecraft assembly clean room, and it has previously demonstrated resistance to UV radiation up to 1000 J/m(sup 2). The EL appears to bind B. horneckiae spores into large aggregations, or biofilms, and may confer some UV resistance to the spores. Multiple culturing and purification schemes were tried to achieve high purity spores because vegetative cells would skew UV resistance results. An ethanol-based purification scheme produced high purity spores. Selective removal of the EL from spores was attempted with two schemes: a chemical extraction method and physical extraction (sonication). Results from survival rates in the presence and absence of the external layer will provide a new understanding of the role of biofilms and passive resistance that may favor survival of biological systems in aggressive extra-terrestrial environments. The chemical extraction method decreased viable counts of spores and lead to an inconclusive change UV resistance relative to non-extracted spores. The physical extraction method lead to non-aggregated spores and did not alter viability; however, it produced UV resistance profiles similar to non-extracted spores. In addition to the EL-removal study, samples of B. horneckiae spores dried on

Aerobic Exercise and Weight Loss Reduce Vascular Markers of Inflammation and Improve Insulin Sensitivity in Obese Women

PubMed Central

Ryan, Alice S.; Ge, Shealinna; Blumenthal, Jacob B.; Serra, Monica C.; Prior, Steven J.; Goldberg, Andrew P.

2014-01-01

Background/Objectives To examine the relationships of plasma and tissue markers of systemic and vascular inflammation to obesity and insulin resistance and determine the effects of aerobic exercise training+weight loss (AEX+WL) and weight loss (WL) on these biomarkers. Design Prospective controlled study. Participants Seventy-seven overweight and obese sedentary postmenopausal women. Interventions Six months, 3d/wk AEX+WL (n=37) or WL (n=40). Measurements Total body dual-energy x-ray absorptiometry, abdominal computed tomography scans, hyperinsulinemic-euglycemic clamps, adipose tissue biopsies (n=28), and blood for Homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule (sICAM-1) and vascular CAM-1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Results Body weight, %fat, visceral fat, triglyceride levels and systolic blood pressure decreased comparably after WL and AEX+WL (P<0.05). VO2max increased 16% after AEX+WL (P<0.001). Insulin resistance decreased in both groups (P<0.01). Glucose utilization increased 10% (P< 0.05) after AEX+WL and 8% with WL (P=0.07). AEX+WL and WL decreased CRP by 29% and 21%, (P<0.05). SAA levels decreased two-fold more after AEX+WL (−19%, P<0.05) than with WL (−9%, P=0.08). Plasma sICAM-1 and sVCAM-1 levels did not change; however, women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose, insulin and insulin resistance (P<0.05). Gluteal ICAM mRNA levels decreased 27% after AEX+WL (P<0.05) and did not change after WL. Conclusion Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP and SAA and tissue ICAM decrease with exercise and weight loss, suggesting that exercise training is a necessary component of lifestyle modification in obese postmenopausal women. PMID:24635342

Cell to cell contact through ICAM-1-LFA-1 and TNF-alpha synergistically contributes to GM-CSF and subsequent cytokine synthesis in DBA/2 mice induced by 1,3-beta-D-Glucan SCG.

PubMed

Harada, Toshie; Kawaminami, Hiromi; Miura, Noriko N; Adachi, Yoshiyuki; Nakajima, Mitsuhiro; Yadomae, Toshiro; Ohno, Naohito

2006-04-01

SCG is a major 6-branched 1,3-beta-D-glucan in Sparassis crispa Fr. showing antitumor activity. We recently found that the splenocytes from naive DBA/1 and DBA/2 mice are potently induced by SCG to produce interferon- gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-12p70 (IL-12p70), and that GM-CSF plays a key biologic role among these cytokines. In this study, we investigated the contribution of cell-cell contact and soluble factors to cytokine induction by SCG in DBA/2 mice. Cell-cell contact involving intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) was an essential step for the induction of GM-CSF and IFN-gamma by SCG but not for the induction of TNF-alpha or IL-12p70 by SCG. SCG directly induced adherent splenocytes to produce TNF-alpha and IL-12p70. GM-CSF was required for the induction of TNF-alpha by SCG, and in turn, TNF-alpha enhanced the release of GM-CSF and thereby augmented the induction of IL-12p70 and IFN-gamma by SCG. Neutralization of IL-12 significantly inhibited the induction of IFN-gamma by SCG. We concluded that induction of GM-CSF production by SCG was mediated through ICAM-1 and LFA-1 interaction, GM-CSF subsequently contributed to further cytokine induction by SCG, and reciprocal actions of the cytokines were essential for enhancement of the overall response to SCG in DBA/2 mice.

Investigation of radiation shielding properties for MeO-PbCl2-TeO2 (MeO = Bi2O3, MoO3, Sb2O3, WO3, ZnO) glasses

NASA Astrophysics Data System (ADS)

Sayyed, M. I.; Çelikbilek Ersundu, M.; Ersundu, A. E.; Lakshminarayana, G.; Kostka, P.

2018-03-01

In this work, glasses in the MeO-PbCl2-TeO2 (MeO = Bi2O3, MoO3, Sb2O3, WO3, ZnO) system, which show a great potential for optoelectronic applications, were used to evaluate their resistance under high energy ionizing radiations. The basic shielding quantities for determining the penetration of radiation in glass, such as mass attenuation coefficient (μ/ρ), half value layer (HVL), mean free path (MFP) and exposure buildup factor (EBF) values were investigated within the energy range 0.015 MeV ‒ 15 MeV using XCOM program and variation of shielding parameters were compared with different glass systems and ordinary concrete. From the derived results, it was determined that MeO-PbCl2-TeO2 (MeO = Bi2O3, MoO3, Sb2O3, WO3, ZnO) glasses show great potentiality to be used under high energy radiations. Among the studied glass compositions, Bi2O3 and WO3 containing glasses were found to possess superior gamma-ray shielding effectiveness.

Development of radiation resistant electrical cable insulations

NASA Technical Reports Server (NTRS)

Lee, B. S.; Soo, P.; Mackenzie, D. R.

1994-01-01

Two new polyethylene cable insulations have been formulated for nuclear applications and have been tested under gamma radiation. Both insulations are based on low density polyethylene, one with PbO and the other with Sb2O3 as additives. The test results show that the concept of using inorganic antioxidants to retard radiation initiated oxidation (RIO) is viable. PbO is more effective than Sb2O3 in minimizing RIO.

Molecular exploration of the highly radiation resistant cyanobacterium Arthrospira sp. PCC 8005

NASA Astrophysics Data System (ADS)

Badri, Hanène; Leys, Natalie; Wattiez, Ruddy

Arthrospira (Spirulina) is a photosynthetic cyanobacterium able to use sunlight to release oxygen from water and remove carbon dioxide and nitrate from water. In addition, it is suited for human consumption (edible). For these traits, the cyanobacterium Arthrospira sp. PCC 8005 was selected by the European Space Agency (ESA) as part of the life support system MELiSSA for recycling oxygen, water, and food during future long-haul space missions. However, during such extended missions, Arthrospira sp. PCC 8005 will be exposed to continuous artificial illumination and harmful cosmic radiation. The aim of this study was to investigate how Arthrospira will react and behave when exposed to such stress environment. The cyanobacterium Arthrospira sp. PCC 8005 was exposed to high gamma rays doses in order to unravel in details the response of this bacterium following such stress. Test results showed that after acute exposure to high doses of 60Co gamma radiation upto 3200 Gy, Arthrospira filaments were still able to restart photosynthesis and proliferate normally. Doses above 3200 Gy, did have a detrimental effect on the cells, and delayed post-irradiation proliferation. The photosystem activity, measured as the PSII quantum yield immediately after irradiation, decreased significantly at radiation doses above 3200 Gy. Likewise through pigment content analysis a significant decrease in phycocyanin was observed following exposure to 3200 Gy. The high tolerance of this bacterium to 60Co gamma rays (i.e. ca. 1000x more resistant than human cells for example) raised our interest to investigate in details the cellular and molecular mechanisms behind this amazing resistance. Optimised DNA, RNA and protein extraction methods and a new microarray chip specific for Arthrospira sp. PCC 8005 were developed to identify the global cellular and molecular response following exposure to 3200 Gy and 5000 Gy A total of 15,29 % and 30,18 % genes were found differentially expressed in RNA

Intestinal and peri-tumoral lymphatic endothelial cells are resistant to radiation-induced apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sung, Hoon Ki; Department of Anatomy, Yeung Nam University Medical School, Daegu 705-717; Morisada, Tohru

2006-06-30

Radiation therapy is a widely used cancer treatment, but it is unable to completely block cancer metastasis. The lymphatic vasculature serves as the primary route for metastatic spread, but little is known about how lymphatic endothelial cells respond to radiation. Here, we show that lymphatic endothelial cells in the small intestine and peri-tumor areas are highly resistant to radiation injury, while blood vessel endothelial cells in the small intestine are relatively sensitive. Our results suggest the need for alternative therapeutic modalities that can block lymphatic endothelial cell survival, and thus disrupt the integrity of lymphatic vessels in peri-tumor areas.

Radiation-hard ceramic Resistive Plate Chambers for forward TOF and T0 systems

NASA Astrophysics Data System (ADS)

Akindinov, A.; Dreyer, J.; Fan, X.; Kämpfer, B.; Kiselev, S.; Kotte, R.; Garcia, A. Laso; Malkevich, D.; Naumann, L.; Nedosekin, A.; Plotnikov, V.; Stach, D.; Sultanov, R.; Voloshin, K.

2017-02-01

Resistive Plate Chambers with ceramic electrodes are the main candidates for a use in precise multi-channel timing systems operating in high-radiation conditions. We report the latest R&D results on these detectors aimed to meet the requirements of the forward T0 counter at the CBM experiment. RPC design, gas mixture, limits on the bulk resistivity of ceramic electrodes, efficiency, time resolution, counting rate capabilities and ageing test results are presented.

Toward advanced gamma rays radiation resistance and shielding efficiency with phthalonitrile resins and composites

NASA Astrophysics Data System (ADS)

Derradji, Mehdi; Zegaoui, Abdeldjalil; Xu, Yi-Le; Wang, An-ran; Dayo, Abdul Qadeer; Wang, Jun; Liu, Wen-bin; Liu, Yu-Guang; Khiari, Karim

2018-04-01

The phthalonitrile resins have claimed the leading place in the field of high performance polymers thanks to their combination of outstanding properties. The present work explores for the first time the gamma rays radiation resistance and shielding efficiency of the phthalonitrile resins and its related tungsten-reinforced nanocomposites. The primary goal of this research is to define the basic behavior of the phthalonitrile resins under highly ionizing gamma rays. The obtained results confirmed that the neat phthalonitrile resins can resist absorbed doses as high as 200 kGy. Meanwhile, the remarkable shielding efficiency of the phthalonitrile polymers was confirmed to be easily improved by preparing lead-free nanocomposites. In fact, the gamma rays screening ratio reached the exceptional value of 42% for the nanocomposites of 50 wt% of nano-tungsten loading. Thus, this study confirms that the remarkable performances of the phthalonitrile resins are not limited to the thermal and mechanical properties and can be extended to the gamma rays radiation and shielding resistances.

Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome

PubMed Central

Takemura, Naoki; Kawasaki, Takumi; Kunisawa, Jun; Sato, Shintaro; Lamichhane, Aayam; Kobiyama, Kouji; Aoshi, Taiki; Ito, Junichi; Mizuguchi, Kenji; Karuppuchamy, Thangaraj; Matsunaga, Kouta; Miyatake, Shoichiro; Mori, Nobuko; Tsujimura, Tohru; Satoh, Takashi; Kumagai, Yutaro; Kawai, Taro; Standley, Daron M.; Ishii, Ken J.; Kiyono, Hiroshi; Akira, Shizuo; Uematsu, Satoshi

2014-01-01

High-dose ionizing radiation induces severe DNA damage in the epithelial stem cells in small intestinal crypts and causes gastrointestinal syndrome (GIS). Although the tumour suppressor p53 is a primary factor inducing death of crypt cells with DNA damage, its essential role in maintaining genome stability means inhibiting p53 to prevent GIS is not a viable strategy. Here we show that the innate immune receptor Toll-like receptor 3 (TLR3) is critical for the pathogenesis of GIS. Tlr3−/− mice show substantial resistance to GIS owing to significantly reduced radiation-induced crypt cell death. Despite showing reduced crypt cell death, p53-dependent crypt cell death is not impaired in Tlr3−/− mice. p53-dependent crypt cell death causes leakage of cellular RNA, which induces extensive cell death via TLR3. An inhibitor of TLR3–RNA binding ameliorates GIS by reducing crypt cell death. Thus, we propose blocking TLR3 activation as a novel approach to treat GIS. PMID:24637670

Orobanche foetida resistance in two new faba bean genotypes produced by radiation mutagenesis.

PubMed

Mejri, Sonia; Mabrouk, Yassine; Belhadj, Omrane; Saidi, Mouldi

2018-06-12

Broomrape produces serious damage to many legume crops and particularly becomes a limiting factor for faba bean (Vicia faba L.) production in the Mediterranean basin. Currently, several traditional methods of control have been developed, but none has proved to be effective for this parasite. However, breeding for resistance to this pest remains as one of the most feasible and environmentally friendly methods for managing broomrape, but the mechanisms governing the interaction between the parasite and the host are not yet well understood. Therefore, we studied behaviours and the molecular and enzymatic changes associated with resistance to Orobanche foetida in faba bean mutants that were obtained through radiation mutagenesis. Three faba bean genotypes were used in this study, the variety 'Badï 'characterized by high productivity in Orobanche-free soils and susceptibility to O. foetida and two mutant lines P2M3 and P7M3 (derived from radio mutagenesis program) selected for their higher resistance to O. foetida in field evaluation. The infection progress and the relative changes in the co culture response, the enzymatic activities changes and the efficiency of the root extract stimulants from the host plant were followed and evaluated in all genotypes. Experiments showed that low induction of seed germination is a major component of resistance in these lines against O. foetida. This is confirmed by in vitro experiments with root exudates. In parallel reduction in infection was accompanied by the continuously enhancement of the peroxidase activity, the polyphenol oxidase activity and the phenylalanine ammonia lyase activity in faba bean roots. These data suggest the contribution of these enzymes in faba bean resistance to O. foetida broomrape induced by the use of gamma rays. Management of Orobanche by way of crop selection based on these enzyme systems is a possible option.

ICAM-1 and AMPK regulate cell detachment and apoptosis by N-methyl-N Prime -nitro-N-nitrosoguanidine, a widely spread environmental chemical, in human hormone-refractory prostate cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yi-Cheng; Lu, Pin-Hsuan; Hsu, Jui-Ling

2011-12-15

Poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, plays a crucial role in the regulation of DNA repair. PARP-1 hyperactivation causes DNA damage and cell death. The underlying mechanism is complicated and is through diverse pathways. The understanding of responsible signaling pathways may offer implications for effective therapies. After concentration-response determination of N-Methyl-N Prime -Nitro-N-Nitrosoguanidine (MNNG, a PARP-1 activating agent and an environmental mutagen) in human hormone-refractory prostate cancers, the data showed that concentrations below 5 {mu}M did not change cell survival but cause a time-dependent up-regulation of intracellular adhesion molecule-1 (ICAM-1) in mRNA, total protein and cell surface levels.more » Detection of phosphorylation and degradation of I{kappa}B-{alpha} and nuclear translocation of NF-{kappa}B showed that MNNG induced the activation of NF-{kappa}B that was responsible for the ICAM-1 up-regulation since PDTC (a NF-{kappa}B inhibitor) significantly abolished this effect. However, higher concentrations (e.g., 10 {mu}M) of MNNG induced a 61% detachment of the cells which were apoptosis associated with the activation of AMP-activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Further identification showed that both AMPK and JNK other than p38 MAPK functionally contributed to cell death. The remaining 39% attached cells were survival associated with high ICAM-1 expression. In conclusion, the data suggest that NF-{kappa}B-dependent up-regulation of ICAM-1 plays a key role on cell attachment and survival; whereas, activation of AMPK and JNK participates in cytotoxic signaling pathways in detached cells caused by PARP-1 activation. Highlights: Black-Right-Pointing-Pointer Low level of DNA damage helps cell attachment and survival via ICAM-1 upregulation. Black-Right-Pointing-Pointer High level of DNA damage causes AMPK- and JNK-involved cell

Design of radiation resistant metallic multilayers for advanced nuclear systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhernenkov, Mikhail, E-mail: zherne@bnl.gov, E-mail: gills@bnl.gov; Gill, Simerjeet, E-mail: zherne@bnl.gov, E-mail: gills@bnl.gov; Stanic, Vesna

2014-06-16

Helium implantation from transmutation reactions is a major cause of embrittlement and dimensional instability of structural components in nuclear energy systems. Development of novel materials with improved radiation resistance, which is of the utmost importance for progress in nuclear energy, requires guidelines to arrive at favorable parameters more efficiently. Here, we present a methodology that can be used for the design of radiation tolerant materials. We used synchrotron X-ray reflectivity to nondestructively study radiation effects at buried interfaces and measure swelling induced by He implantation in Cu/Nb multilayers. The results, supported by transmission electron microscopy, show a direct correlation betweenmore » reduced swelling in nanoscale multilayers and increased interface area per unit volume, consistent with helium storage in Cu/Nb interfaces in forms that minimize dimensional changes. In addition, for Cu/Nb layers, a linear relationship is demonstrated between the measured depth-dependent swelling and implanted He density from simulations, making the reflectivity technique a powerful tool for heuristic material design.« less

Electron-hole pairs generated in ZrO2 nanoparticle resist upon exposure to extreme ultraviolet radiation

NASA Astrophysics Data System (ADS)

Kozawa, Takahiro; Santillan, Julius Joseph; Itani, Toshiro

2018-02-01

Metal oxide nanoparticle resists have attracted much attention as the next-generation resist used for the high-volume production of semiconductor devices. However, the sensitization mechanism of the metal oxide nanoparticle resists is unknown. Understanding the sensitization mechanism is important for the efficient development of resist materials. In this study, the energy deposition in a zirconium oxide (ZrO2) nanoparticle resist was investigated. The numbers of electron-hole pairs generated in a ZrO2 core and an methacrylic acid (MAA) ligand shell upon exposure to 1 mJ cm-2 (exposure dose) extreme ultraviolet (EUV) radiations were theoretically estimated to be 0.16 at most and 0.04-0.17 cm2 mJ-1, respectively. By comparing the calculated distribution of electron-hole pairs with the line-and-space patterns of the ZrO2 nanoparticle resist fabricated by an EUV exposure tool, the number of electron-hole pairs required for the solubility change of the resist films was estimated to be 1.3-2.2 per NP. NP denotes a nanoparticle consisting of a metal oxide core with a ligand shell. In the material design of metal oxide nanoparticle resists, it is important to efficiently use the electron-hole pairs generated in the metal oxide core for the chemical change of ligand molecules.

Atomistic structures of nano-engineered SiC and radiation-induced amorphization resistance

NASA Astrophysics Data System (ADS)

Imada, Kenta; Ishimaru, Manabu; Sato, Kazuhisa; Xue, Haizhou; Zhang, Yanwen; Shannon, Steven; Weber, William J.

2015-10-01

Nano-engineered 3C-SiC thin films, which possess columnar structures with high-density stacking faults and twins, were irradiated with 2 MeV Si ions at cryogenic and room temperatures. From cross-sectional transmission electron microscopy observations in combination with Monte Carlo simulations based on the Stopping and Range of Ions in Matter code, it was found that their amorphization resistance is six times greater than bulk crystalline SiC at room temperature. High-angle bright-field images taken by spherical aberration corrected scanning transmission electron microscopy revealed that the distortion of atomic configurations is localized near the stacking faults. The resultant strain field probably contributes to the enhancement of radiation tolerance of this material.

Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKβ pathways.

PubMed

Zhao, Wenwen; Wu, Chuanhong; Li, Shaojing; Chen, Xiuping

2016-12-01

Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated with PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-α, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expression and protein-protein interaction were determined by western blotting and immunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKKβ, p-IκBα, p-p65 expression, and p-IκBα-IKKβ interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-κB inhibitor PDTC showed similar effect on PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin-triggered expression of p-IRS-1(Tyr), p-PI3K, p-AKT, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKKβ pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dichromatic and monochromatic laser radiation effects on antibiotic resistance, biofilm formation, and division rate of Pantoea agglomerans

NASA Astrophysics Data System (ADS)

Thomé, A. M. C.; Souza, B. P.; Mendes, J. P. M.; Cardoso, A. F. R.; Soares, L. C.; Trajano, E. T. L.; Fonseca, A. S.

2018-06-01

Since infection is a common cause of delayed wound healing, it is important to understand the effect of low-level laser therapy (LLLT) in bacterial mechanisms. In this study we evaluated the effects of LLLT on antibiotic resistance, division rate, and biofilm formation of Pantoea agglomerans. P. agglomerans samples were isolated from human pressure injuries in humans and cultures were exposed to low-level monochromatic and simultaneous dichromatic laser radiation to study the susceptibility of an antimicrobial to ampicillin and piperacillin  +  tazobactam, quantification of areas of bacterial colonies, and biofilm formation of bacterial cells. Fluence, wavelength, and emission mode were used in the therapeutic protocols for wound healing. The data showed no changes in the areas of the colonies, but dichromatic laser radiation decreased biofilm formation, while a monochromatic red laser at low dose increased biofilm formation and infrared at high dose decreased antibiotic resistance to ampicillin. LLLT modulates antibiotic resistance and biofilm formation of P. agglomerans, but these depend on the laser irradiation parameters, since dichromatic laser radiation induces biological effects that differ from those induced by monochromatic laser radiation. Thus, simultaneous dichromatic low-level red and infrared lasers could be a new option for the treatment of infected wounds, reducing biofilm formation, without altering antibiotic resistance and the division rate of P. agglomerans cultures.

Role of Dendritic Cell-Specific ICAM-3-Grabbing Nonintegrin on Dendritic Cells in the Recognition of Hepatitis B Virus.

PubMed

Wang, Minxin; Zou, Xiaojing; Tian, Deying; Hu, Song; Jiang, Libin

2015-01-01

Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an essential process for virus infection, such as HIV and hepatitis C, and plays a role in immune escape. However, the role of DC-SIGN in hepatitis B virus (HBV) infection is still unknown. The aim of this study was to investigate the role of DC-SIGN in mediating the maturation and activation of dendritic cells (DCs) when infected by HBV. Highly mannosylated HBV particles were obtained by treating HBV-producing HepG2.2.15 cells with the a-mannosidase I-inhibitor kifunensine. Highly mannosylated HBV or wild type HBV was added to infect the DCs of the DC-SIGN gene-silencing group and normal group, respectively. Then, the expression of CDla, CD80, CD83, CD86 and HLA-DR on DCs was detected by flow cytometry, the capacity of stimulating lymphocyte proliferation was tested by MTT assay, the level of IL-12p70 that was released by DCs was measured by enzyme-linked immunosorbent assay, and the expression of the proteins NF-κBp65 and p38 was detected by western blot. Both wild type and highly mannosylated HBV could promote DCs maturation and activation. However, the highly mannosylated HBV could promote DCs immune activation more strongly. The difference in the effect on DCs between the two types of HBV could be eliminated by DC-SIGN gene silencing. DC-SIGN can promote the maturation and activation of DCs when recognized HBV, but wild type HBV can escape recognition by DC-SIGN to a certain extent with the help of demannosylated modification, leading to defective DCs function and chronic HBV infection.

A temperature correlation for the radiation resistance of a thick-walled circular duct exhausting a hot gas

NASA Technical Reports Server (NTRS)

Mahan, J. R.; Cline, J. G.; Jones, J. D.

1984-01-01

It is often useful to know the radiation impedance of an unflanged but thick-walled circular duct exhausting a hot gas into relatively cold surroundings. The reactive component is shown to be insensitive to temperature, but the resistive component is shown to be temperature dependent. A temperature correlation is developed permitting prediction of the radiation resistance from a knowledge of the temperature difference between the ambient air and the gas flowing from the duct, and a physical basis for this correlation is presented.

Radiation resistance of oxide dispersion strengthened alloys: Perspectives from in situ observations and rate theory calculations

DOE PAGES

Liu, Xiang; Miao, Yinbin; Li, Meimei; ...

2018-04-15

Here, in situ ion irradiation and rate theory calculations were employed to directly compare the radiation resistance of an oxide dispersion strengthened alloy with that of a conventional ferritic/martensitic alloy. Compared to the rapid buildup of dislocation loops, loop growth, and formation of network dislocations in the conventional ferritic/martensitic alloy, the superior radiation resistance of the oxide dispersion strengthened alloy is manifested by its stable dislocation structure under the same irradiation conditions. Thus, the results are consistent with rate theory calculations, which show that high-density nanoparticles can significantly reduce freely migrating defects and suppress the buildup of clustered defects.

Radiation resistance of oxide dispersion strengthened alloys: Perspectives from in situ observations and rate theory calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiang; Miao, Yinbin; Li, Meimei

Here, in situ ion irradiation and rate theory calculations were employed to directly compare the radiation resistance of an oxide dispersion strengthened alloy with that of a conventional ferritic/martensitic alloy. Compared to the rapid buildup of dislocation loops, loop growth, and formation of network dislocations in the conventional ferritic/martensitic alloy, the superior radiation resistance of the oxide dispersion strengthened alloy is manifested by its stable dislocation structure under the same irradiation conditions. Thus, the results are consistent with rate theory calculations, which show that high-density nanoparticles can significantly reduce freely migrating defects and suppress the buildup of clustered defects.

The effects of low-level ionizing radiation and copper exposure on the incidence of antibiotic resistance in lentic biofilm bacteria.

PubMed

McArthur, J Vaun; Dicks, Christian A; Bryan, A Lawrence; Tuckfield, R Cary

2017-09-01

Environmental reservoirs of antibiotic resistant bacteria are poorly understood. Understanding how the environment selects for resistance traits in the absence of antibiotics is critical in developing strategies to mitigate this growing menace. Indirect or co-selection of resistance by environmental pollution has been shown to increase antibiotic resistance. However no attention has been given to the effects of low-level ionizing radiation or the interactions between radiation and heavy metals on the maintenance or selection for antibiotic resistance (AR) traits. Here we explore the effect of radiation and copper on antibiotic resistance. Bacteria were collected from biofilms in two ponds - one impacted by low-level radiocesium and the other an abandoned farm pond. Through laboratory controlled experiments we examined the effects of increasing concentrations of copper on the incidence of antibiotic resistance. Differences were detected in the resistance profiles of the controls from each pond. Low levels (0.01 mM) of copper sulfate increased resistance but 0.5 mM concentrations of copper sulfate depressed the AR response in both ponds. A similar pattern was observed for levels of multiple antibiotic resistance per isolate. The first principal component response of isolate exposure to multiple antibiotics showed significant differences among the six isolate treatment combinations. These differences were clearly visualized through a discriminant function analysis, which showed distinct antibiotic resistance response patterns based on the six treatment groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

A low-power, radiation-resistant, Silicon-Drift-Detector array for extraterrestrial element mapping

NASA Astrophysics Data System (ADS)

Ramsey, B. D.; Gaskin, J. A.; Elsner, R. F.; Chen, W.; Carini, G. A.; De Geronimo, G.; Keister, J.; Li, S.; Li, Z.; Siddons, D. P.; Smith, G.

2012-02-01

We are developing a modular Silicon Drift Detector (SDD) X-Ray Spectrometer (XRS) for measuring the abundances of light surface elements (C to Fe) fluoresced by ambient radiation on remote airless bodies. The value of fluorescence spectrometry for surface element mapping is demonstrated by its inclusion on three recent lunar missions and by exciting new data that have recently been announced from the Messenger Mission to Mercury. The SDD-XRS instrument that we have been developing offers excellent energy resolution and an order of magnitude lower power requirement than conventional CCDs, making much higher sensitivities possible with modest spacecraft resources. In addition, it is significantly more radiation resistant than x-ray CCDs and therefore will not be subject to the degradation that befell recent lunar instruments. In fact, the intrinsic radiation resistance of the SDD makes it applicable even to the harsh environment of the Jovian system where it can be used to map the light surface elements of Europa. In this paper, we first discuss our element-mapping science-measurement goals. We then derive the necessary instrument requirements to meet these goals and discuss our current instrument development status with respect to these requirements.

Development of single nanometer-sized ultrafine oxygen bubbles to overcome the hypoxia-induced resistance to radiation therapy via the suppression of hypoxia-inducible factor-1α

PubMed Central

Honma, Kyoko; Nakano, Takashi; Asao, Takayuki; Kuwahara, Ryusuke; Aoyama, Kazuhiro; Yasuda, Hidehiro; Kelly, Matthew; Kuwano, Hiroyuki

2018-01-01

Radiation therapy can result in severe side-effects, including the development of radiation resistance. The aim of this study was to validate the use of oxygen nanobubble water to overcome resistance to radiation in cancer cell lines via the suppression of the hypoxia-inducible factor 1-α (HIF-1α) subunit. Oxygen nanobubble water was created using a newly developed method to produce nanobubbles in the single-nanometer range with the ΣPM-5 device. The size and concentration of the oxygen nanobubbles in the water was examined using a cryo-transmission electron microscope. The nanobubble size was ranged from 2 to 3 nm, and the concentration of the nanobubbles was calculated at 2×1018 particles/ml. Cell viability and HIF-1α levels were evaluated in EBC-1 lung cancer and MDA-MB-231 breast cancer cells treated with or without the nanobubble water and radiation under normoxic and hypoxic conditions in vitro. The cancer cells grown in oxygen nanobubble-containing media exhibited a clear suppression of hypoxia-induced HIF-1α expression compared to the cells grown in media made with distilled water. Under hypoxic conditions, the EBC-1 and MDA-MB231 cells displayed resistance to radiation compared to the cells cultured under normoxic cells. The use of oxygen nanobubble medium significantly suppressed the hypoxia-induced resistance to radiation compared to the use of normal medium at 2, 6, 10 and 14 Gy doses. Importantly, the use of nanobubble media did not affect the viability and radiation sensitivity of the cancer cell lines, or the non-cancerous cell line, BEAS-2B, under normoxic conditions. This newly created single-nanometer range oxygen nanobubble water, without any additives, may thus prove to be a promising agent which may be used to overcome the hypoxia-induced resistance of cancer cells to radiation via the suppression of HIF-1α. PMID:29393397

Sunlight-Exposed Biofilm Microbial Communities Are Naturally Resistant to Chernobyl Ionizing-Radiation Levels

PubMed Central

Ragon, Marie; Restoux, Gwendal; Moreira, David; Møller, Anders Pape; López-García, Purificación

2011-01-01

Background The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. Methodology/Principal Findings To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. Conclusions/Significance Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general

Sunlight-exposed biofilm microbial communities are naturally resistant to chernobyl ionizing-radiation levels.

PubMed

Ragon, Marie; Restoux, Gwendal; Moreira, David; Møller, Anders Pape; López-García, Purificación

2011-01-01

The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general diversity patterns, despite increased mutation levels at the single

RNA Nanoparticles Derived from Three-Way Junction of Phi29 Motor pRNA Are Resistant to I-125 and Cs-131 Radiation

PubMed Central

Li, Hui; Rychahou, Piotr G.; Cui, Zheng; Pi, Fengmei; Evers, B. Mark; Shu, Dan

2015-01-01

Radiation reagents that specifically target tumors are in high demand for the treatment of cancer. The emerging field of RNA nanotechnology might provide new opportunities for targeted radiation therapy. This study investigates whether chemically modified RNA nanoparticles derived from the packaging RNA (pRNA) three-way junction (3WJ) of phi29 DNA-packaging motor are resistant to potent I-125 and Cs-131 radiation, which is a prerequisite for utilizing these RNA nanoparticles as carriers for targeted radiation therapy. pRNA 3WJ nanoparticles were constructed and characterized, and the stability of these nanoparticles under I-125 and Cs-131 irradiation with clinically relevant doses was examined. RNA nanoparticles derived from the pRNA 3WJ targeted tumors specifically and they were stable under irradiation of I-125 and Cs-131 with clinically relevant doses ranging from 1 to 90 Gy over a significantly long time up to 20 days, while control plasmid DNA was damaged at 20 Gy or higher. PMID:26017686

Effect of solar radiation on multidrug resistant E. coli strains and antibiotic mixture photodegradation in wastewater polluted stream.

PubMed

Rizzo, L; Fiorentino, A; Anselmo, A

2012-06-15

The effect of solar radiation on the inactivation of multidrug resistant Escherichia coli (MDR) strains selected from an urban wastewater treatment plant (UWWTP) effluent and the change of their resistance to a mixture of three antibiotics (evaluated in terms of minimum inhibit concentration (MIC)) in wastewater polluted stream were investigated. The solar photodegradation of the mixture of the three target antibiotics (amoxicillin (AMX), ciprofloxacin (CPX), and sulfamethoxazole (SMZ)) was also evaluated. Additionally, since UWWTP effluents are possible sources of antibiotics and antibiotic resistant bacteria, the disinfection by conventional chlorination process of the UWWTP effluent inoculated with MDR strains was investigated too. Solar radiation poorly affected the inactivation of the two selected antibiotic resistant E. coli strains (40 and 60% after 180 min irradiation). Moreover, solar radiation did not affect strain resistance to AMX (MIC>256 μg/mL) and SMZ (MIC>1024 μg/mL), but affected resistance of the lower resistance strain to CPX (MIC decreased by 33% but only after 180 min of irradiation). Chlorination of wastewater sample strongly decreased the number of the two selected antibiotic resistant E. coli strains (99.667 and 99.999%), after 60 min of contact time at 2.0 mg/L initial chlorine concentration, but the resistance of survived colonies to antibiotics was unchanged. Finally, the solar photodegradation rate of the antibiotic mixture (1mg/L initial concentration respectively) resulted in the following order (half-life time): CPX (t(1/2)=24 min)resistance to SMZ in surface water is significantly higher compared to CPX and AMX. Copyright © 2012 Elsevier B.V. All rights reserved.

Gd2O3:Eu3+/PPO/POPOP/PS composites for digital imaging radiation detectors

NASA Astrophysics Data System (ADS)

Oliveira, J.; Martins, P. M.; Martins, P.; Correia, V.; Rocha, J. G.; Lanceros-Mendez, S.

2015-11-01

Polymer-based scintillator composites have been produced by combining polystyrene (PS) and Gd2O3:Eu3+ scintillator nanoparticles. Polystyrene has been used since it is a flexible and stable binder matrix, resistant to thermal and light deterioration and with suitable optical properties. Gd2O3:Eu3+ has been selected as scintillator material due to its wide band gap, high density and visible light yield. The optical, thermal and electrical characteristics of the composites were studied as a function of filler content, together with their performance as scintillator material. Additionally 1 wt.% of 2,5-diphenyloxazole (PPO) and 0.01 wt.% of 1,4 di[2-(5phenyloxazolyl)]benzene (POPOP) were introduced in the polymer matrix in order to strongly improve light yield, i.e., the measured intensity of the output visible radiation, under X-ray irradiation. Increasing scintillator filler concentration (from 0.25 to 7.5 wt.%) increases scintillator light yield and decreases the optical transparency of the composite. The addition of PPO and POPOP strongly increased the overall transduction performance of the composite due to specific absorption and re-emission processes. It is thus shown that Gd2O3:Eu3+/PPO/POPOP/PS composites with 0.25 wt.% of scintillator content with fluorescence molecules are suitable for the development of innovative large-area X-ray radiation detectors with huge demand from the industries.

Atomistic structures of nano-engineered SiC and radiation-induced amorphization resistance

DOE PAGES

Imada, Kenta; Ishimaru, Manabu; Sato, Kazuhisa; ...

2015-06-18

In this paper, nano-engineered 3C–SiC thin films, which possess columnar structures with high-density stacking faults and twins, were irradiated with 2 MeV Si ions at cryogenic and room temperatures. From cross-sectional transmission electron microscopy observations in combination with Monte Carlo simulations based on the Stopping and Range of Ions in Matter code, it was found that their amorphization resistance is six times greater than bulk crystalline SiC at room temperature. High-angle bright-field images taken by spherical aberration corrected scanning transmission electron microscopy revealed that the distortion of atomic configurations is localized near the stacking faults. Finally, the resultant strain fieldmore » probably contributes to the enhancement of radiation tolerance of this material.« less

Radiation-resistant microorganism

DOEpatents

Fliermans, Carl B.

2007-01-09

An isolated and purified bacterium is provided which was isolated from a high-level radioactive waste site of mixed waste. The isolate has the ability to degrade a wide variety of organic contaminants while demonstrating high tolerance to ionizing radiation. The organism is uniquely suited to bioremediation of a variety or organic contaminants while in the presence of ionizing radiation.

Radiation-resistant microorganism

DOEpatents

Fliermans, Carl B.

2010-06-15

An isolated and purified bacterium is provided which was isolated from a high-level radioactive waste site of mixed waste. The isolate has the ability to degrade a wide variety of organic contaminants while demonstrating high tolerance to ionizing radiation. The organism is uniquely suited to bioremediation of a variety or organic contaminants while in the presence of ionizing radiation.

Patterns of cell division, DNA base compositions, and fine structures of some radiation-resistant vegetative bacteria found in food

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanders, S.W.; Maxcy, R.B.

1979-01-01

Representative highly radiation-resistant Moraxella-Acinetobacter (M-A), Pseudomonas radiora, Micrococcus radiodurans, and Micrococcus radiophilus exhibited a wide variety of division systems and cell wall characteristics. However, the more resistant M-A possessed unusually thick cell walls, indicating a possible role of the cell wall in radiation resistance in the M-A. Thick septation was present in most of the bacteria studied, but was absent in P. radiora, thus excluding this as a necessity for high resistance. Reliable determination of the number of division planes of the M-A for use as a taxonomic criterion was achieved by the direct observation of dividing cells. The highlymore » resistant M-A were found to divide in multiple planes and had base compositions of 54.0 to 57.5%, unlike typical Moraxella and/or Acinetobacter species. The taxonomic position of most highly resistant bacteria remains unclear.« less

Comparison of the effects of Crataegus oxyacantha extract, aerobic exercise and their combination on the serum levels of ICAM-1 and E-Selectin in patients with stable angina pectoris.

PubMed

Jalaly, Leila; Sharifi, Gholamreza; Faramarzi, Mohammad; Nematollahi, Alireza; Rafieian-kopaei, Mahmoud; Amiri, Masoud; Moattar, Fariborz

2015-12-19

Adhesion molecules play an important role in the development and progression of coronary atherosclerosis. The aim of this study was comparing the effect of Cratagol herbal tablet, aerobic exercise and their combination on the serum levels of Intercellular adhesion molecule (ICAM)-1 and E-Selectin in patients with stable angina pectoris. Eighty stable angina pectoris patients aged between 45 and 65 years, were randomly divided into four groups including three experimental groups and one control group: aerobic exercise (E), Crataegus oxyacantha extract (S), aerobic exercise and Crataegus oxyacantha extract (S+E), and control (C). Blood sampling was taken 24 h before and after 12 weeks of aerobic exercise and Crataegus oxyacantha extract consumption. The results of serum levels of ICAM-1 and E-selectin were compared. Intergroup comparison of the data revealed a significant reduction (P <0.01) in serum levels of ICAM-1 and E-selectin in experimental groups. Analysis of data showed that the serum levels of ICAM-1 had significant difference when group S+E was compared with groups S and C, but not group E (P = 0.021, P = 0.000 and P = 0.068, respectively). Also the difference between the levels of E-selectin was significant comparing S+E and S but not E with group C (P = 0.021, P = 0.000 and P = 0.052, respectively). Twelve weeks effects of aerobic exercise and Crataegus oxyacantha extract consuming is an effective complementary strategy to significantly lower the risk of atherosclerosis and heart problems.

Superior radiation-resistant nanoengineered austenitic 304L stainless steel for applications in extreme radiation environments

NASA Astrophysics Data System (ADS)

Sun, C.; Zheng, S.; Wei, C. C.; Wu, Y.; Shao, L.; Yang, Y.; Hartwig, K. T.; Maloy, S. A.; Zinkle, S. J.; Allen, T. R.; Wang, H.; Zhang, X.

2015-01-01

Nuclear energy provides more than 10% of electrical power internationally, and the increasing engagement of nuclear energy is essential to meet the rapid worldwide increase in energy demand. A paramount challenge in the development of advanced nuclear reactors is the discovery of advanced structural materials that can endure extreme environments, such as severe neutron irradiation damage at high temperatures. It has been known for decades that high dose radiation can introduce significant void swelling accompanied by precipitation in austenitic stainless steel (SS). Here we report, however, that through nanoengineering, ultra-fine grained (UFG) 304L SS with an average grain size of ~100 nm, can withstand Fe ion irradiation at 500°C to 80 displacements-per-atom (dpa) with moderate grain coarsening. Compared to coarse grained (CG) counterparts, swelling resistance of UFG SS is improved by nearly an order of magnitude and swelling rate is reduced by a factor of 5. M23C6 precipitates, abundant in irradiated CG SS, are largely absent in UFG SS. This study provides a nanoengineering approach to design and discover radiation tolerant metallic materials for applications in extreme radiation environments.

Superior radiation-resistant nanoengineered austenitic 304L stainless steel for applications in extreme radiation environments

DOE PAGES

Sun, C.; Zheng, S.; Wei, C. C.; ...

2015-01-15

Nuclear energy provides more than 10% of electrical power internationally, and the increasing engagement of nuclear energy is essential to meet the rapid worldwide increase in energy demand. A paramount challenge in the development of advanced nuclear reactors is the discovery of advanced structural materials that can endure extreme environments, such as severe neutron irradiation damage at high temperatures. It has been known for decades that high dose radiation can introduce significant void swelling accompanied by precipitation in austenitic stainless steel (SS). Here we report, however, that through nanoengineering, ultra-fine grained (UFG) 304L SS with an average grain size ofmore » ~100 nm, can withstand Fe ion irradiation at 500°C to 80 displacements-per-atom (dpa) with moderate grain coarsening. Compared to coarse grained (CG) counterparts, swelling resistance of UFG SS is improved by nearly an order of magnitude and swelling rate is reduced by a factor of 5. M₂₃C₆ precipitates, abundant in irradiated CG SS, are largely absent in UFG SS. This study provides a nanoengineering approach to design and discover radiation tolerant metallic materials for applications in extreme radiation environments.« less

Superior radiation-resistant nanoengineered austenitic 304L stainless steel for applications in extreme radiation environments.

PubMed

Sun, C; Zheng, S; Wei, C C; Wu, Y; Shao, L; Yang, Y; Hartwig, K T; Maloy, S A; Zinkle, S J; Allen, T R; Wang, H; Zhang, X

2015-01-15

Nuclear energy provides more than 10% of electrical power internationally, and the increasing engagement of nuclear energy is essential to meet the rapid worldwide increase in energy demand. A paramount challenge in the development of advanced nuclear reactors is the discovery of advanced structural materials that can endure extreme environments, such as severe neutron irradiation damage at high temperatures. It has been known for decades that high dose radiation can introduce significant void swelling accompanied by precipitation in austenitic stainless steel (SS). Here we report, however, that through nanoengineering, ultra-fine grained (UFG) 304 L SS with an average grain size of ~100 nm, can withstand Fe ion irradiation at 500 °C to 80 displacements-per-atom (dpa) with moderate grain coarsening. Compared to coarse grained (CG) counterparts, swelling resistance of UFG SS is improved by nearly an order of magnitude and swelling rate is reduced by a factor of 5. M(23)C(6) precipitates, abundant in irradiated CG SS, are largely absent in UFG SS. This study provides a nanoengineering approach to design and discover radiation tolerant metallic materials for applications in extreme radiation environments.

Superior radiation-resistant nanoengineered austenitic 304L stainless steel for applications in extreme radiation environments

PubMed Central

Sun, C.; Zheng, S.; Wei, C. C.; Wu, Y.; Shao, L.; Yang, Y.; Hartwig, K. T.; Maloy, S. A.; Zinkle, S. J.; Allen, T. R.; Wang, H.; Zhang, X.

2015-01-01

Nuclear energy provides more than 10% of electrical power internationally, and the increasing engagement of nuclear energy is essential to meet the rapid worldwide increase in energy demand. A paramount challenge in the development of advanced nuclear reactors is the discovery of advanced structural materials that can endure extreme environments, such as severe neutron irradiation damage at high temperatures. It has been known for decades that high dose radiation can introduce significant void swelling accompanied by precipitation in austenitic stainless steel (SS). Here we report, however, that through nanoengineering, ultra-fine grained (UFG) 304L SS with an average grain size of ~100 nm, can withstand Fe ion irradiation at 500°C to 80 displacements-per-atom (dpa) with moderate grain coarsening. Compared to coarse grained (CG) counterparts, swelling resistance of UFG SS is improved by nearly an order of magnitude and swelling rate is reduced by a factor of 5. M23C6 precipitates, abundant in irradiated CG SS, are largely absent in UFG SS. This study provides a nanoengineering approach to design and discover radiation tolerant metallic materials for applications in extreme radiation environments. PMID:25588326

Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses

PubMed Central

Velasquez, Lis Noelia; Stüve, Philipp; Gentilini, Maria Virginia; Swallow, Maxine; Bartel, Judith; Lycke, Nils Yngve; Barkan, Daniel; Martina, Mariana; Lujan, Hugo D.; Kalay, Hakan; van Kooyk, Yvette; Sparwasser, Tim D.; Berod, Luciana

2018-01-01

Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections. PMID:29662482

Growth, spectroscopy, and laser performance of a 2.79 μm Cr,Er,Pr:GYSGG radiation-resistant crystal.

PubMed

Luo, Jianqiao; Sun, Dunlu; Zhang, Huili; Guo, Qiang; Fang, Zhongqing; Zhao, Xuyao; Cheng, Maojie; Zhang, Qingli; Yin, Shaotang

2015-09-15

We demonstrate the growth, spectroscopy, and laser performance of a 2.79 μm Cr,Er,Pr:GYSGG radiation-resistant crystal. The lifetimes for the upper laser level (4)I(11/2) and lower laser level (4)I(13/2) are 0.59 and 0.84 ms, respectively, which are due to the doping of the Pr(3+) ions. A maximum pulse energy of 278 mJ operated at 10 Hz and 2.79 μm is obtained when pumped with a flash lamp, which corresponds to the electrical-to-optical efficiency of 0.6% and a slope efficiency of 0.7%. A maximum average power of 2.9 W at 60 Hz is achieved, which corresponds to the electrical-to-optical efficiency of 0.4% and slope efficiency of 0.8%. Compared with a Cr,Er:YSGG crystal, the Cr,Er,Pr:GYSGG crystal can be operated at a higher pulse repetition rate. These results suggest that doping deactivator Pr(3+) ions can effectively decrease the lower laser level lifetime and improve the laser repetition rate. Therefore, the application fields and range of the Cr,Er,Pr:GYSGG laser can be extended greatly due to its properties of radiation resistance and high repetition frequency.

Selective Insulin-like Growth Factor Resistance Associated with Heart Hemorrhages and Poor Prognosis in a Novel Preclinical Model of the Hematopoietic Acute Radiation Syndrome.

PubMed

Kenchegowda, Doreswamy; Legesse, Betre; Hritzo, Bernadette; Olsen, Cara; Aghdam, Saeed; Kaur, Amandeep; Culp, William; Derrien-Colemyn, Alexandrine; Severson, Grant; Moroni, Maria

2018-05-29

Although bone marrow aplasia has been considered for the past decades as the major contributor of radiation-induced blood disorders, cytopenias alone are insufficient to explain differences in the prevalence of bleeding. In this study, the minipig was used as a novel preclinical model of hematopoietic acute radiation syndrome to assess if factors other than platelet counts correlated with bleeding and survival. We sought to determine whether radiation affected the insulin-like growth factor-1 (IGF-1) pathway, a growth hormone with cardiovascular and radioprotective features. Gottingen and Sinclair minipigs were exposed to ionizing radiation at hematopoietic doses. The smaller Gottingen minipig strain was more sensitive to radiation; differences in IGF-1 levels were minimal, suggesting that increased sensitivity could depend on weak response to the hormone. Radiation caused IGF-1 selective resistance by inhibiting the anti-inflammatory anti-oxidative stress IRS/PI3K/Akt but not the pro-inflammatory MAPK kinase pathway, shifting IGF-1 signaling towards a pro-oxidant, pro-inflammatory environment. Selective IGF-1 resistance associated with hemorrhages in the heart, poor prognosis, increase in C-reactive protein and NADPH oxidase 2, uncoupling of endothelial nitric oxide synthase, inhibition of nitric oxide (NO) synthesis and imbalance between the vasodilator NO and the vasoconstrictor endothelin-1 molecules. Selective IGF-1 resistance is a novel mechanism of radiation injury, associated with a vicious cycle amplifying reactive oxygen species-induced damage, inflammation and endothelial dysfunction. In the presence of thrombocytopenia, selective inhibition of IGF-1 cardioprotective function may contribute to the development of hemostatic disorders. This finding may be particularly relevant for individuals with low IGF-1 activity, such as the elderly or those with cardiometabolic dysfunctions.

Hammerhead Ribozyme against γ‐Glutamylcysteine Synthetase Attenuates Resistance to Ionizing Radiation and Cisplatin in Human T98G Glioblastoma Cells

PubMed Central

Tani, Masaharu; Goto, Shinji; Kamada, Kensaku; Mori, Katsuharu; Urata, Yoshishige; Ihara, Yoshito; Kijima, Hiroshi; Ueyama, Yoshito; Shibata, Shobu

2002-01-01

Glioblastoma cells are highly malignant and show resistance to ionizing radiation, as well as anti‐cancer drugs. This resistance to cancer therapy is often associated with a high concentration of glutathione (GSH). In this study, the effect of continuous down‐regulation of γ‐glutamylcysteine synthetase (γ‐GCS) expression, a rate‐limiting enzyme for GSH synthesis, on resistance to ionizing radiation and cisplatin (CDDP) was studied in T98G human glioblastoma cells. We constructed a hammerhead ribozyme against a γ‐GCS heavy subunit (γ‐GCSh) mRNA and transfected it into T98G cells. (1) The transfection of the ribozyme decreased the concentration of GSH and resulted in G1 cell cycle arrest of T98G cells. (2) The transfection of the ribozyme increased the cytotoxicity of ionizing radiation and CDDP in T98G cells. Thus, hammerhead ribozyme against γ‐GCS is suggested to have potential as a cancer gene therapy to reduce the resistance of malignant cells to ionizing radiation and anti‐cancer drugs. PMID:12079521

Aerobic exercise and weight loss reduce vascular markers of inflammation and improve insulin sensitivity in obese women.

PubMed

Ryan, Alice S; Ge, Shealinna; Blumenthal, Jacob B; Serra, Monica C; Prior, Steven J; Goldberg, Andrew P

2014-04-01

To examine the relationships between plasma and tissue markers of systemic and vascular inflammation and obesity and insulin resistance and determine the effects of aerobic exercise training plus weight loss (AEX+WL) and weight loss (WL) alone on these biomarkers. Prospective controlled study. Veterans Affairs Medical Center and University research setting. Overweight and obese sedentary postmenopausal women (N = 77). Six months, 3 d/wk AEX+WL (n = 37) or WL (n = 40). Total-body dual-energy X-ray absorptiometry, abdominal computed tomography, hyperinsulinemic-euglycemic clamps (a criterion standard method of assessing insulin sensitivity), adipose tissue biopsies (n = 28), and blood for homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Body weight (P < .001), percentage of fat (P < .001), visceral fat (P < .005), triglyceride levels (P < .001), and systolic blood pressure decreased comparably after WL and AEX+WL (P = .04). Maximal oxygen consumption increased 16% after AEX+WL (P < .001). Insulin resistance decreased in both groups (P = .005). Glucose utilization according to the clamp increased 10% (P = .04) with AEX+WL and 8% with WL (P = .07). AEX+WL decreased CRP by 29% (P < .001) and WL by 21% (P = .02). SAA levels decreased twice as much after AEX+WL (-19%, P = .02) as after WL (-9%, P = .08). Plasma sICAM-1 and sVCAM-1 levels did not change, but women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose (P = .02), insulin (P = .02), and insulin resistance (P = .004). Gluteal ICAM messenger ribonucleic acid levels decreased 27% after AEX+WL (P = .02) and did not change after WL. Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP, SAA, and

THE CROSS-RESISTANCE TO PENICILLIN AND RADIATION OF ESCHERICHIA COLI B (in Hungarian)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kutas, V.

The radiosensitivity of cultures resistant to 1500 IU/ml, 2000 IU/ml, 2500 IU/ml of penicillin, produced from strain E. coli B was examined. Cultures in the log-phase were streaked in monocellular layers on the agar surface and x irradiation was applied. As a result of penicillin treatment cell filaments consisting of several members were formed. Measuring the effect of ionizing radiation by the percentage survival, the cultures resistant to penicillin proved to be considerably more radioresistant than the parent strain B, non-treated with penicillin. (auth)

A Low-Power, Radiation-Resistant, Silicon-Drift-Detector Array for Extraterrestrial Element Mapping

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramsey B. D.; De Geronimo G.; Gaskin, J.A.

2012-02-08

We are developing a modular Silicon Drift Detector (SDD) X-Ray Spectrometer (XRS) for measuring the abundances of light surface elements (C to Fe) fluoresced by ambient radiation on remote airless bodies. The value of fluorescence spectrometry for surface element mapping is demonstrated by its inclusion on three recent lunar missions and by exciting new data that have recently been announced from the Messenger Mission to Mercury. The SDD-XRS instrument that we have been developing offers excellent energy resolution and an order of magnitude lower power requirement than conventional CCDs, making much higher sensitivities possible with modest spacecraft resources. In addition,more » it is significantly more radiation resistant than x-ray CCDs and therefore will not be subject to the degradation that befell recent lunar instruments. In fact, the intrinsic radiation resistance of the SDD makes it applicable even to the harsh environment of the Jovian system where it can be used to map the light surface elements of Europa. In this paper, we first discuss our element-mapping science-measurement goals. We then derive the necessary instrument requirements to meet these goals and discuss our current instrument development status with respect to these requirements.« less

Mutants of feline immunodeficiency virus resistant to 2',3'-dideoxy-2',3'-didehydrothymidine.

PubMed Central

Zhu, Y Q; Remington, K M; North, T W

1996-01-01

We selected mutants of feline immunodeficiency virus (FIV) that are resistant to 2',3'-dideoxy-2',3'-didehydrothymidine (d4T). Two mutants were selected in cultured cells with a stepwise increase in d4T concentration, resulting in mutants able to replicate in 100 microM d4T. These mutants were three- to sixfold more resistant to d4T than wild-type FIV. They were also cross-resistant to 3'-azido-3'-deoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine, 2',3'-dideoxycytidine, 2',3'-dideoxyinosine, and 9-(2-phosphonylmethoxyethyl)adenine, and they were highly resistant to phosphonoformic acid (PFA). Plaque-purified mutants were isolated from each of the mutant populations. The mutant phenotype was stable, because both of the plaque-purified mutants remained d4T resistant even after three passages in the absence of d4T. One of the plaque-purified mutants, designated D4R-3c, was further characterized. Compared with wild-type reverse transcriptase (RT), RT purified from D4R-3c was 3-fold resistant to inhibition by the 5'-triphosphate of d4T, 10-fold resistant to inhibition by the 5'-triphosphate of AZT, and 6-fold resistant to PFA. D4R-3c had a single point mutation in the RT-encoding region of the pol gene at position 2474, resulting in a Val to Ile mutation at codon 47 of the FIV RT. The role of this mutation in d4T resistance was confirmed by site-directed mutagenesis. PMID:8878567

Fast Resistive Bolometry

NASA Astrophysics Data System (ADS)

Graham, Jeffrey

2005-10-01

A bolometer with microsecond scale response time is under construction for the Caltech spheromak experiment to measure radiation from a ˜20 μs duration plasma discharge emitting ˜10^2---10^3 kW/m^2. A gold film several micrometers thick absorbs the radiation, heats up, and the consequent change in resistance can be measured. The film itself is vacuum deposited upon a glass slide. Several geometries for the film are under consideration to optimize the amount of radiation absorbed, the response time and the signal-to-noise ratio. We measure the change in voltage across the film for a known current driven through it; a square pulse (3---30A, ˜20 μs) is used to avoid Joule heating. Results from prototypes tested with a UV flashlamp will be presented. After optimizing the bolometer design, the final vacuum-compatible diagnostic would consist of a plasma-facing bolometer and a reference in a camera obscura. This device could provide a design for fast resistive bolometry.

Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru; Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru; Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head andmore » neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.« less

Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron

NASA Astrophysics Data System (ADS)

Musabaeva, L. I.; Startseva, Zh. A.; Gribova, O. V.; Velikaya, V. V.; Lisin, V. A.

2016-08-01

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head and neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.

RACK1 promotes radiation resistance in esophageal cancer via regulating AKT pathway and Bcl-2 expression.

PubMed

Liu, Bowen; Wang, Cong; Chen, Pengxiang; Wang, Lu; Cheng, Yufeng

2017-09-23

RACK1 is a seven Trp-Asp 40 repeat protein, which interacts with a wide range of kinases and proteins. RACK1 plays an important role in the proliferation and progression of various cancers. The aim of this study is to detect the role of RACK1 in the radioresistance in esophageal cancer. The results indicated that downregulation of RACK1 reduced the colony formation ability, proliferation ability and resistance of cells to radiation effection through regulating the radiation-related proteins including pAKT, Bcl-2 and Bim; whereas upregulation of RACK1 promoted the ability and radioresistance of ESCC cells. Our findings suggest that RACK1 promotes proliferation and radioresistance in ESCC cells by activating the AKT pathway, upregulating Bcl-2 expression and downregulating protein levels of Bim. Our study fills in gaps in the field of RACK1 and radiation resistance and may provide new possibilities for improving strategies of radiotherapy in esophageal cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

A patient-specific computational model of hypoxia-modulated radiation resistance in glioblastoma using 18F-FMISO-PET

PubMed Central

Rockne, Russell C.; Trister, Andrew D.; Jacobs, Joshua; Hawkins-Daarud, Andrea J.; Neal, Maxwell L.; Hendrickson, Kristi; Mrugala, Maciej M.; Rockhill, Jason K.; Kinahan, Paul; Krohn, Kenneth A.; Swanson, Kristin R.

2015-01-01

Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient's disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [18F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning. PMID:25540239

The radiation balance of the earth-atmosphere system from Nimbus 3 radiation measurements

NASA Technical Reports Server (NTRS)

Raschke, E.; Vonderhaar, T. H.; Pasternak, M.; Bandeen, W. R.

1973-01-01

The radiation balance of the earth-atmosphere system and its components was computed from global measurements of radiation reflected and emitted from the earth to space. These measurements were made from the meteorological satellite Nimbus 3 during the periods from April 16 to August 15, 1969; October 3 to 17, 1969; and January 21 to February 3, 1970. Primarily the method of evaluation, its inherent assumptions, and possible error sources were discussed. Results are presented by various methods: (1) global, hemispherical, and zonal averages obtained from measurements in all semimonthly periods and (2) global maps of the absorbed solar radiation, the albedo, the outgoing longwave radiation, and the radiation balance obtained from measurements during semimonthly periods in each season (May 1 to 15, July 16 to 31, and October 3 to 17, 1969, and January 21 to February 3, 1970). Annual global averages of the albedo and of the outgoing longwave radiation were determined. These values balance to within 1 percent the annual global energy input by solar radiation that was computed for a solar constant.

[Study of serum levels of interlukin-2 and its receptor, interlukin-6, sICAM-1, sVCAM-1 in patients with recurrent genital herpes].

PubMed

Zhang, Min; Zhang, Yizhi

2003-01-01

To study cellular immunity status and serum levels of adhesion molecules of patients with recurrent genital herpes. Serum levels of interlukin-2 and its soluble receptor, interlukin-6, sICAM-1, sVCAM-1 were measured by ELISA in 34 patients with recurrent genital herpes. The serum levels of IL-2 and IL-6 were significantly lower in patients than in healthy controls (P < 0.01). The levels of sIL-2R, sICAM-1 and sVCAM-1 were significantly higher in patients than in controls (P < 0.05). No significant differences were seen in all variables of patients in relapse phase and remission phase (P > 0.05). There are cellular immunity deficiency and high serum levels of adhesion molecules in patients with recurrent genital herpes, and these changes may be related to therecurrence of genital herpes and the development of inflammatory reaction.

Increased resistance to ionizing and ultraviolet radiation in Escherichia coli JM83 is associated with a chromosomal rearrangement.

PubMed

McLean, K M; Gutman, P D; Minton, K W; Clark, E P

1992-06-01

Cells cope with radiation damage through several mechanisms: (1) increased DNA repair activity, (2) scavenging and inactivation of radiation-induced radical molecules, and (3) entry into a G0-like quiescent state. We have investigated a chromosomal rearrangement to elucidate further the molecular and genetic mechanisms underlying these phenomena. A mutant of Escherichia coli JM83 (phi 80dlacZ delta M15) was isolated that demonstrated significantly increased resistance to both ionizing and ultraviolet radiation. Surviving fractions of mutant and wild-type cells were measured following exposure to standardized doses of radiation. Increased radioresistance was directly related to a chromosomal alteration near the bacteriophage phi 80 attachment site (attB), as initially detected by the LacZ- phenotype of the isolate. Southern hybridization of chromosomal DNA from the mutant and wild-type E. coli JM83 strains indicated that a deletion had occurred. We propose that the deletion near the attB locus produces the radioresistant phenotype of the E. coli JM83 LacZ- mutant, perhaps through the alteration or inactivation of a gene or its controlling element(s).

Can low-level laser therapy (LLLT) associated with an aerobic plus resistance training change the cardiometabolic risk in obese women? A placebo-controlled clinical trial.

PubMed

Duarte, Fernanda Oliveira; Sene-Fiorese, Marcela; de Aquino Junior, Antonio Eduardo; da Silveira Campos, Raquel Munhoz; Masquio, Deborah Cristina Landi; Tock, Lian; Garcia de Oliveira Duarte, Ana Claudia; Dâmaso, Ana Raimunda; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

2015-12-01

Obesity is one of the most important link factors to coronary artery disease development mainly due to the pro-inflammatory and pro-thrombotic states favoring atherosclerosis progression. The LLLT acts in the cellular metabolism and it is highly effective to improve inflammation. The same occur in response to different kinds of exercise. However, we have not known the associate effects using LLLT therapies with aerobic plus resistance training as strategy specifically with target at human obesity control and its comorbidities. Investigate the effects of the LLLT associated with aerobic plus resistance training on cardiometabolic risk factors in obese women. Women aged 20-40 years (BMI ≥ 30 kg/m(2)), were divided into 2 groups: Phototherapy (PHOTO) and Placebo. They were trained aerobic plus resistance exercises (in a concurrent mode), 1h, 3 times/week during 16 weeks. Phototherapy was applied after each exercise session for 16 min, with infrared laser, wavelength 808 nm, continuous output, power 100 mW, and energy delivery 50 J. The body composition was measured with bioimpedance. Inflammatory mark concentrations were measured using a commercially available multiplex. LLLT associated with aerobic plus resistance training was effective in decrease neck (P=0.0003) and waist circumferences (P=0.02); percentual of fat (P=0.04); visceral fat area (P=0.02); HOMA-IR (P=0.0009); Leptin (P=0.03) and ICAM (P=0.03). Also, the reduction in leptin (P=0.008) and ICAM-1 (0, 05) was much more expressive in the phototherapy group in comparison to placebo group when analyzed by delta values. LLLT associated with concurrent exercise (aerobic plus resistance training) potentiates the exercise effects of decreasing the cardiometabolic risk factors in obese woman. These results suggest the LLLT associated with exercises as a new therapeutic tool in the control of obesity and its comorbidities for obese people, targeting to optimize the strategies to control the cardiometabolic risk

Identifying the Proteins that Mediate the Ionizing Radiation Resistance of Deinococcus Radiodurans R1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battista, John R

The primary objectives of this proposal was to define the subset of proteins required for the ionizing radiation (IR) resistance of Deinococcus radiodurans R1, characterize the activities of those proteins, and apply what was learned to problems of interest to the Department of Energy.

RAD18 mediates resistance to ionizing radiation in human glioma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xie, Chen; Wang, Hongwei; Cheng, Hongbin

Highlights: • RAD18 is an important mediator of the IR-induced resistance in glioma cell lines. • RAD18 overexpression confers resistance to IR-mediated apoptosis. • The elevated expression of RAD18 is associated with recurrent GBM who underwent IR therapy. - Abstract: Radioresistance remains a major challenge in the treatment of glioblastoma multiforme (GBM). RAD18 a central regulator of translesion DNA synthesis (TLS), has been shown to play an important role in regulating genomic stability and DNA damage response. In the present study, we investigate the relationship between RAD18 and resistance to ionizing radiation (IR) and examined the expression levels of RAD18more » in primary and recurrent GBM specimens. Our results showed that RAD18 is an important mediator of the IR-induced resistance in GBM. The expression level of RAD18 in glioma cells correlates with their resistance to IR. Ectopic expression of RAD18 in RAD18-low A172 glioma cells confers significant resistance to IR treatment. Conversely, depletion of endogenous RAD18 in RAD18-high glioma cells sensitized these cells to IR treatment. Moreover, RAD18 overexpression confers resistance to IR-mediated apoptosis in RAD18-low A172 glioma cells, whereas cells deficient in RAD18 exhibit increased apoptosis induced by IR. Furthermore, knockdown of RAD18 in RAD18-high glioma cells disrupts HR-mediated repair, resulting in increased accumulation of DSB. In addition, clinical data indicated that RAD18 was significantly higher in recurrent GBM samples that were exposed to IR compared with the corresponding primary GBM samples. Collectively, our findings reveal that RAD18 may serve as a key mediator of the IR response and may function as a potential target for circumventing IR resistance in human GBM.« less

Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice.

PubMed

Henry, Scott P; Levin, Arthur A; White, Kimber; Mennear, John H

2006-12-01

ISIS 2302 is a phosphorothioate oligonucleotide designed to inhibit human ICAM-1 and is intended for treatment of inflammatory diseases. Molecules of this class are known to elicit pro-inflammatory effects, and immunotoxicity studies were performed in mice to elucidate the nature of effects of ISIS 2302 on mammalian immune function. ISIS 2302 (1, 5, 20, or 50 mg/kg/dose) was administered intravenously every other day for 27 days. The pro-inflammatory properties of the drug were observed at doses > or = 20 mg/kg. A dose-dependent increase in spleen weight was associated with increased absolute splenocyte and B-lymphocyte counts after the 50 mg/kg/dose regimen. The mitogenic response of B-lymphocytes to bacterial lipopolysaccharide was increased after the 20 and 50 mg/kg/doses but antibody-forming cell activities remained unchanged. Total serum IgG concentration was decreased after the 20 and 50 mg/kg/dose regimens but IgM titers were unchanged. Increases in IL-6, IL-12, and MCP-1 as well as NK cell activity were observed after administration of 20 and 50 mg/kg/dose. Cytotoxic T-lymphocyte activity was decreased by the 50 mg/kg/dose regimen. Other changes in immune function were not observed in ISIS 2302-dosed mice. ISIS 3082, a murine active ICAM-1 inhibitor, was used to demonstrate the anti-inflammatory activity of ICAM-1 inhibition in the 2,4-dinitrofluorobenzene-induced contact sensitization model. Intravenous administration of 1 mg/kg of ISIS 3082 every other day for 27 days was unequivocally anti-inflammatory in the contact sensitization test. The results of these experiments support the conclusion that the prophlogistic effects of ISIS 2302 in mice are observed only at suprapharmacologic doses.

Enhanced Radiation Resistance of Methanosarcina soligelidi SMA-21, a New Methanogenic Archaeon Isolated from a Siberian Permafrost-Affected Soil in Direct Comparison to Methanosarcina barkeri.

PubMed

Morozova, Daria; Moeller, Ralf; Rettberg, Petra; Wagner, Dirk

2015-11-01

Permafrost-affected soils are characterized by a high abundance and diversity of methanogenic communities, which are considered suitable model organisms for potential life on Mars. Methanogens from Siberian permafrost have been proven to be highly resistant against divers stress conditions such as subzero temperatures, desiccation, and simulated thermophysical martian conditions. Here, we studied the radiation resistance of the currently described new species Methanosarcina soligelidi SMA-21, which was isolated from a Siberian permafrost-affected soil, in comparison to Methanosarcina barkeri, which is used as a reference organism from a nonpermafrost soil environment. Both strains were exposed to solar UV and ionizing radiation to assess their limits of survival. Methanosarcina soligelidi exhibit an increase in radiation resistance to UV (2.5- to 13.8-fold) and ionizing radiation (46.6-fold) compared to M. barkeri. The F10 (UVC) and D10 (X-rays) values of M. soligelidi are comparable to values for the well-known, highly radioresistant species Deinococcus radiodurans. In contrast, the radiation response of M. barkeri was highly sensitive to UV and ionizing radiation comparably to Escherichia coli and other radiosensitive microorganisms. This study showed that species of the same genus respond differently to UV and ionizing radiation, which might reflect the adaptation of Methanosarcina soligelidi SMA-21 to the harsh environmental conditions of the permafrost habitat. Methanogenic archaea-Environmental UV-Ionizing radiation-Permafrost-Radiation resistance-Mars.

Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

NASA Technical Reports Server (NTRS)

Patel, Z. S.; Cucinotta, F. A.; Huff, J. L.

2011-01-01

Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would

High-Efficiency Thin-Film Silicon-on-GaP Solar Cell for Improved Radiation Resistance.

DTIC Science & Technology

1987-09-01

UNCLASSIFIED MyUM 21 LIX E / 82H M D 132 11111_Lt5l1. t FILE UPI" AD-A190 268 AFWAL-TR-87-2070 HIGH-EFFICIENCY THIN- FILM SILICON-ON-GaP SOLAR CELL...EFFICIENCY THIN- FILM SILICON-ON-GaP SOLAR CELL FOR IMPROVED RADIATION RESISTANCE 12. PERSONAL AUTHOR(S) JEROME S. CULIK 13a. TYPE OF REPORT 13b. TIME...C tinue on reverse if necessary and identify by block number) 10 01 SILICONs THIN* FILM , . HETEROEPITAXIAL, RADIATION, 10 01 i GALLIUM PHOSPHIDE 19

Radiation Tolerant Interfaces: Influence of Local Stoichiometry at the Misfit Dislocation on Radiation Damage Resistance of Metal/Oxide Interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shutthanandan, Vaithiyalingam; Choudhury, Samrat; Manandhar, Sandeep

The interaction of radiation with materials controls the performance, reliability, and safety of many structures in nuclear power systems. Revolutionary improvements in radiation damage resistance may be attainable if methods can be found to manipulate interface properties to give optimal interface stability and point defect recombination capability. To understand how variations in interface properties such as misfit dislocation density and local chemistry affect radiation-induced defect absorption and recombination, a model system of metallic Cr xV 1-x (0 ≤ x ≤ 1) epitaxial films deposited on MgO(001) single crystal substrates has been explored in this paper. By controlling film composition, themore » lattice mismatch between the film and MgO is adjusted to vary the misfit dislocation density at the metal/oxide interface. The stability of these interfaces under various irradiation conditions is studied experimentally and theoretically. The results indicate that, unlike at metal/metal interfaces, the misfit dislocation density does not dominate radiation damage tolerance at metal/oxide interfaces. Rather, the stoichiometry and the location of the misfit dislocation extra half-plane (in the metal or the oxide) drive radiation-induced defect behavior. Finally, together, these results demonstrate the sensitivity of defect recombination to interfacial chemistry and provide new avenues for engineering radiation-tolerant nanomaterials for next-generation nuclear power plants.« less

Radiation Tolerant Interfaces: Influence of Local Stoichiometry at the Misfit Dislocation on Radiation Damage Resistance of Metal/Oxide Interfaces

DOE PAGES

Shutthanandan, Vaithiyalingam; Choudhury, Samrat; Manandhar, Sandeep; ...

2017-04-24

The interaction of radiation with materials controls the performance, reliability, and safety of many structures in nuclear power systems. Revolutionary improvements in radiation damage resistance may be attainable if methods can be found to manipulate interface properties to give optimal interface stability and point defect recombination capability. To understand how variations in interface properties such as misfit dislocation density and local chemistry affect radiation-induced defect absorption and recombination, a model system of metallic Cr xV 1-x (0 ≤ x ≤ 1) epitaxial films deposited on MgO(001) single crystal substrates has been explored in this paper. By controlling film composition, themore » lattice mismatch between the film and MgO is adjusted to vary the misfit dislocation density at the metal/oxide interface. The stability of these interfaces under various irradiation conditions is studied experimentally and theoretically. The results indicate that, unlike at metal/metal interfaces, the misfit dislocation density does not dominate radiation damage tolerance at metal/oxide interfaces. Rather, the stoichiometry and the location of the misfit dislocation extra half-plane (in the metal or the oxide) drive radiation-induced defect behavior. Finally, together, these results demonstrate the sensitivity of defect recombination to interfacial chemistry and provide new avenues for engineering radiation-tolerant nanomaterials for next-generation nuclear power plants.« less

Radiation resistance of a gamma-ray irradiated nonlinear optic chromophore

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Taylor, Edward W.

2009-11-01

The radiation resistance of organic electro-optic and optoelectronic materials for space applications is receiving increased attention. An earlier investigation reported that guest-host poled polymer EO modulator devices composed of a phenyltetraene bridge-type chromophore in amorphous polycarbonate (CLD/APC) did not exhibit a decrease in EO response (i.e., an increase in modulation-switching voltage- Vπ) following irradiation by low dose [10-160 krad(Si)] 60Co gamma-rays. To provide further evidences to the observed radiation stability, the post-irradiation responses of 60Co gamma-rays on CLD1/APC thin films are examined by various chemical and spectroscopic methods including: a solubility test, thin-layer chromatography, proton nuclear magnetic resonance spectroscopy, UV-vis absorption, and infra-red absorption. The results indicate that CLD1 and APC did not decompose under gamma-ray irradiation at dose levels ranging from 66-274 krad(Si) and from 61-154 krad(Si), respectively which support the previously reported data.

Multiplicity of genome equivalents in the radiation-resistant bacterium Micrococcus radiodurans.

PubMed Central

Hansen, M T

1978-01-01

The complexity of the genome of Micrococcus radiodurans was determined to be (2.0 +/- 0.3) X 10(9) daltons by DNA renaturation kinetics. The number of genome equivalents of DNA per cell was calculated from the complexity and the content of DNA. A lower limit of four genome equivalents per cell was approached with decreasing growth rate. Thus, no haploid stage appeared to be realized in this organism. The replication time was estimated from the kinetics and amount of residual DNA synthesis after inhibiting initiation of new rounds of replication. From this, the redundancy of terminal genetic markers was calculated to vary with growth rate from four to approximately eight copies per cell. All genetic material, including the least abundant, is thus multiply represented in each cell. The potential significance of the maintenance in each cell of multiple gene copies is discussed in relation to the extreme radiation resistance of M. radiodurans. PMID:649572

Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopwood, L.E.; Davies, B.M.; Moulder, J.E.

1990-09-01

RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance ismore » seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance.« less

The Survival and Resistance of Halobacterium salinarum NRC-1, Halococcus hamelinensis, and Halococcus morrhuae to Simulated Outer Space Solar Radiation.

PubMed

Leuko, S; Domingos, C; Parpart, A; Reitz, G; Rettberg, P

2015-11-01

Solar radiation is among the most prominent stress factors organisms face during space travel and possibly on other planets. Our analysis of three different halophilic archaea, namely Halobacterium salinarum NRC-1, Halococcus morrhuae, and Halococcus hamelinensis, which were exposed to simulated solar radiation in either dried or liquid state, showed tremendous differences in tolerance and survivability. We found that Hcc. hamelinensis is not able to withstand high fluences of simulated solar radiation compared to the other tested organisms. These results can be correlated to significant differences in genomic integrity following exposure, as visualized by random amplified polymorphic DNA (RAPD)-PCR. In contrast to the other two tested strains, Hcc. hamelinensis accumulates compatible solutes such as trehalose for osmoprotection. The addition of 100 mM trehalose to the growth medium of Hcc. hamelinensis improved its survivability following exposure. Exposure of cells in liquid at different temperatures suggests that Hbt. salinarum NRC-1 is actively repairing cellular and DNA damage during exposure, whereas Hcc. morrhuae exhibits no difference in survival. For Hcc. morrhuae, the high resistance against simulated solar radiation may be explained with the formation of cell clusters. Our experiments showed that these clusters shield cells on the inside against simulated solar radiation, which results in better survival rates at higher fluences when compared to Hbt. salinarum NRC-1 and Hcc. hamelinensis. Overall, this study shows that some halophilic archaea are highly resistant to simulated solar radiation and that they are of high astrobiological significance. Halophiles-Solar radiation-Stress resistance-Survival.

3-Halo Chloroquine Derivatives Overcome Plasmodium falciparum Chloroquine Resistance Transporter-Mediated Drug Resistance in P. falciparum.

PubMed

Edaye, Sonia; Tazoo, Dagobert; Bohle, D Scott; Georges, Elias

2015-12-01

Polymorphism in the Plasmodium falciparum chloroquine resistance transporter (PfCRT) was shown to cause chloroquine resistance. In this report, we examined the antimalarial potential of novel 3-halo chloroquine derivatives (3-chloro, 3-bromo, and 3-iodo) against chloroquine-susceptible and -resistant P. falciparum. All three derivatives inhibited the proliferation of P. falciparum; with 3-iodo chloroquine being most effective. Moreover, 3-iodo chloroquine was highly effective at potentiating and reversing chloroquine toxicity of drug-susceptible and -resistant P. falciparum. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Enhanced radiation resistant fiber optics

DOEpatents

Lyons, Peter B.; Looney, Larry D.

1993-01-01

A process for producing an optical fiber having enhanced radiation resitance is provided, the process including maintaining an optical fiber within a hydrogen-containing atmosphere for sufficient time to yield a hydrogen-permeated optical fiber having an elevated internal hydrogen concentration, and irradiating the hydrogen-permeated optical fiber at a time while the optical fiber has an elevated internal hydrogen concentration with a source of ionizing radiation. The radiation source is typically a cobalt-60 source and the fiber is pre-irradiated with a dose level up to about 1000 kilorads of radiation.

Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells.

PubMed

Yang, Po-Min; Wu, Zhi-Zhen; Zhang, Yu-Qi; Wung, Being-Sun

2016-06-15

Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells. We exposed ARPE-19 cells to TNFα after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-κB nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA. Lycopene could reduce TNF-α-induced monocyte adhesion and H2O2- induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-κB activation for up to 12h in TNFα-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-α-induced ICAM-1 expression and NF-κB activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-α-induced ROS production was abolished. The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-κB activation in lycopene-treated ARPE-19 cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Solomon, Melani; Schuchman, Edward H; Muro, Silvia

2017-07-05

Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Radiation resistant PIDECα cell using photon intermediate direct energy conversion and a 210Po source.

PubMed

Weaver, Charles L; Schott, Robert J; Prelas, Mark A; Wisniewski, Denis A; Rothenberger, Jason B; Lukosi, Eric D; Oh, Kyuhak

2018-02-01

Radiation damage is a significant concern with both alphavoltaic and betavoltaic cells because their performance degrades, especially with high-energy - (>200keV) beta and alpha particles. Indirect excitation methods, such as the Photon Intermediate Direct Energy Conversion (PIDEC) framework, can protect the transducer from radiation. A nuclear battery using a 90 Sr beta source was constructed by the author's research group, which demonstrated the radiation resistance of a PIDEC cell driven by beta particles (PIDECβ cell). Use of alpha sources to drive nuclear batteries would appear to be much more attractive than beta sources due to higher potential power density. However, they are also subject to higher rates of radiation damage. This paper describes the successful incorporation of alpha particles into the PIDEC framework using the alpha emitter 210 Po to form a PIDECα cell. The PIDECα cell transducer was exposed to alpha particles for over one year without experiencing adverse effects from radiation damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiation resistance of nonlinear crystals at a wavelength of 9.55 {mu}m

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andreev, Yu M; Voevodin, V G; Badikov, Valerii V

2001-12-31

The results of radiation resistance measurements for twelve nonlinear crystals are presented. The crystals include the well-known nonlinear CdGeAs{sub 2}, ZnGeP{sub 2}, AgGaSe{sub 2}, GaSe, AgGaS{sub 2}, and Ag{sub 3}AsS{sub 3} crystals operating in the middle IR range, new mixed AgGaGeS{sub 4} and Cd{sub 0.35}Hg{sub 0.65}Ga{sub 2}S{sub 4} crystals, two-phase (orange and yellow) HgGa{sub 2}S{sub 4} crystal, and the doped GaSe:In crystal. The mixed crystals and the two-phase HgGa{sub 2}S{sub 4} crystal are transparent in the range from 0.4 - 0.5 to 11.5 - 14.5 {mu}m. The measurements were performed using a pulsed single-mode highly stability TEA CO{sub 2} lasermore » with an output pulse duration of {approx}30 ns. The damage thresholds of new nonlinear AgGaGeS{sub 4} and Cd {sub 0.35}Hg{sub 0.65}Ga{sub 2}S{sub 4} crystals and of the HgGa{sub 2}S{sub 4} crystal (the orange and yellow phases) were found to be 1.5 - 2.2 times higher than for the crystals operating in the middle IR range. (interaction of laser radiation with matter. laser plasma)« less

Study of surface properties of ATLAS12 strip sensors and their radiation resistance

NASA Astrophysics Data System (ADS)

Mikestikova, M.; Allport, P. P.; Baca, M.; Broughton, J.; Chisholm, A.; Nikolopoulos, K.; Pyatt, S.; Thomas, J. P.; Wilson, J. A.; Kierstead, J.; Kuczewski, P.; Lynn, D.; Hommels, L. B. A.; Ullan, M.; Bloch, I.; Gregor, I. M.; Tackmann, K.; Hauser, M.; Jakobs, K.; Kuehn, S.; Mahboubi, K.; Mori, R.; Parzefall, U.; Clark, A.; Ferrere, D.; Sevilla, S. Gonzalez; Ashby, J.; Blue, A.; Bates, R.; Buttar, C.; Doherty, F.; McMullen, T.; McEwan, F.; O'Shea, V.; Kamada, S.; Yamamura, K.; Ikegami, Y.; Nakamura, K.; Takubo, Y.; Unno, Y.; Takashima, R.; Chilingarov, A.; Fox, H.; Affolder, A. A.; Casse, G.; Dervan, P.; Forshaw, D.; Greenall, A.; Wonsak, S.; Wormald, M.; Cindro, V.; Kramberger, G.; Mandić, I.; Mikuž, M.; Gorelov, I.; Hoeferkamp, M.; Palni, P.; Seidel, S.; Taylor, A.; Toms, K.; Wang, R.; Hessey, N. P.; Valencic, N.; Hanagaki, K.; Dolezal, Z.; Kodys, P.; Bohm, J.; Stastny, J.; Bevan, A.; Beck, G.; Milke, C.; Domingo, M.; Fadeyev, V.; Galloway, Z.; Hibbard-Lubow, D.; Liang, Z.; Sadrozinski, H. F.-W.; Seiden, A.; To, K.; French, R.; Hodgson, P.; Marin-Reyes, H.; Parker, K.; Jinnouchi, O.; Hara, K.; Sato, K.; Hagihara, M.; Iwabuchi, S.; Bernabeu, J.; Civera, J. V.; Garcia, C.; Lacasta, C.; Marti i Garcia, S.; Rodriguez, D.; Santoyo, D.; Solaz, C.; Soldevila, U.

2016-09-01

A radiation hard n+-in-p micro-strip sensor for the use in the Upgrade of the strip tracker of the ATLAS experiment at the High Luminosity Large Hadron Collider (HL-LHC) has been developed by the "ATLAS ITk Strip Sensor collaboration" and produced by Hamamatsu Photonics. Surface properties of different types of end-cap and barrel miniature sensors of the latest sensor design ATLAS12 have been studied before and after irradiation. The tested barrel sensors vary in "punch-through protection" (PTP) structure, and the end-cap sensors, whose stereo-strips differ in fan geometry, in strip pitch and in edge strip ganging options. Sensors have been irradiated with proton fluences of up to 1×1016 neq/cm2, by reactor neutron fluence of 1×1015 neq/cm2 and by gamma rays from 60Co up to dose of 1 MGy. The main goal of the present study is to characterize the leakage current for micro-discharge breakdown voltage estimation, the inter-strip resistance and capacitance, the bias resistance and the effectiveness of PTP structures as a function of bias voltage and fluence. It has been verified that the ATLAS12 sensors have high breakdown voltage well above the operational voltage which implies that different geometries of sensors do not influence their stability. The inter-strip isolation is a strong function of irradiation fluence, however the sensor performance is acceptable in the expected range for HL-LHC. New gated PTP structure exhibits low PTP onset voltage and sharp cut-off of effective resistance even at the highest tested radiation fluence. The inter-strip capacitance complies with the technical specification required before irradiation and no radiation-induced degradation was observed. A summary of ATLAS12 sensors tests is presented including a comparison of results from different irradiation sites. The measured characteristics are compared with the previous prototype of the sensor design, ATLAS07.

High-efficiency, radiation-resistant GaAs space cells

NASA Technical Reports Server (NTRS)

Bertness, K. A.; Ristow, M. Ladle; Grounner, M.; Kuryla, M. S.; Werthen, J. G.

1991-01-01

Although many GaAs solar cells are intended for space applicatons, few measurements of cell degradation after radiation are available, particularly for cells with efficiencies exceeding 20 percent (one-sun, AMO). Often the cell performance is optimized for the highest beginning-of-life (BOL) efficiency, despite the unknown effect of such design on end-of-life (EOL) efficiencies. The results of a study of the radiation effects on p-n GaAs cells are presented. The EOL efficiency of GaAs space cell can be increased by adjusting materials growth parameters, resulting in a demonstration of 16 percent EOL efficiency at one-sun, AMO. Reducing base doping levels to below 3 x 10(exp 17)/cu m and decreasing emitter thickness to 0.3 to 0.5 micron for p-n cells led to significant improvements in radiation hardness as measured by EOL/BOL efficiency ratios for irradiation of 10(exp -15)/sq cm electrons at 1 MeV. BOL efficiency was not affected by changes in emitter thickness but did improve with lower base doping.

Oxygen ingress study of 3D printed gaseous radiation detector enclosures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steer, Christopher A.; Durose, Aaron

2015-07-01

As part of our ongoing studies into the potential application of 3D printing techniques to gaseous radiation detectors, we have studied the ability of 3D printed enclosures to resist environmental oxygen ingress. A set of cuboid and hexagonal prism shaped enclosures with wall thicknesses of 4 mm, 6 mm, 8 mm and 10 mm were designed and printed in nylon using a EOSINT P 730 Selective Laser Sintering 3D printer system These test enclosures provide a comparison of different environmental gas ingress for different 3D printing techniques. The rate of change of oxygen concentration was found to be linear, decreasingmore » as the wall thickness increases. It was also found that the hexagonal prism geometry produced a lower rate of change of oxygen concentration compared with the cuboid shaped enclosures. Possible reasons as to why these results were obtained are discussed The implications for the this study for deployable systems are also discussed (authors)« less

Magnolol inhibits tumor necrosis factor-α-induced ICAM-1 expression via suppressing NF-κB and MAPK signaling pathways in human lung epithelial cells.

PubMed

Chunlian, Wu; Heyong, Wang; Jia, Xu; Jie, Huang; Xi, Chen; Gentao, Liu

2014-12-01

Magnolol is a traditional Chinese medicine from the root and bark of Magnolia officinalis. It has long been used to treat anxiety, cough, headache and allergies, as well as a variety of inflammations. Lung inflammation is a key event in the pathogenesis of asthma and chronic obstructive pulmonary disease. The present study sought to examine the effects of magnolol on tumor necrosis factor (TNF)-α-induced upregulation of intercellular adhesion molecule-1 (ICAM-1), activation of the nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathway in cultured human pulmonary epithelial cells, and adhesion of human macrophage-like U937 cells to A549 cells. A549 cells were incubated with magnolol at 25 and 50 μmol/l. Then, 20 ng/ml TNF-α was used to activate the cells. Magnolol inhibited the growth of human pulmonary epithelial A549 cells in a dose- and time-dependent manner. Magnolol suppressed the adhesion of U937 cells to TNF-α-induced A549 cells. In cultured human pulmonary epithelial A549 cells, magnolol decreased TNF-α-induced upregulation of ICAM-1. Magnolol repressed TNF-α-induced activation of NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in A549 cells by inhibiting phosphorylation of NF-κB, p38, extracellular signal-regulated kinase (ERK) 1/2, and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK). These findings support the hypothesis that magnolol inhibits the inflammatory process in lung epithelial A549 cells by suppressing the ICAM-1 and NF-κB and MAPK signaling pathways. Taken together, these results indicate that magnolol offers significant potential as a therapeutic treatment for inflammatory diseases of the lungs including asthma, sepsis, and chronic obstructive pulmonary disease.

Evolution of radiation defect and radiation hardening in heat treated SA508 Gr3 steel

NASA Astrophysics Data System (ADS)

Jin, Hyung-Ha; Kwon, Junhyun; Shin, Chansun

2014-01-01

The formation of radiation defects and corresponding radiation hardening in heat-treated SA508 Gr3 steel after Fe ion irradiation were investigated by means of transmission electron microscopy and a nano-indentation technique. As the residual dislocation density is increased in the matrix, the formation of radiation defects is considerably weakened. Comparison between the characteristics of the radiation defect and an evaluation of radiation hardening indicates that a large dislocation loop contributes little to the radiation hardening in the heat-treated SA508 Gr3 steel.

Design principles for radiation-resistant solid solutions

NASA Astrophysics Data System (ADS)

Schuler, Thomas; Trinkle, Dallas R.; Bellon, Pascal; Averback, Robert

2017-05-01

We develop a multiscale approach to quantify the increase in the recombined fraction of point defects under irradiation resulting from dilute solute additions to a solid solution. This methodology provides design principles for radiation-resistant materials. Using an existing database of solute diffusivities, we identify Sb as one of the most efficient solutes for this purpose in a Cu matrix. We perform density-functional-theory calculations to obtain binding and migration energies of Sb atoms, vacancies, and self-interstitial atoms in various configurations. The computed data informs the self-consistent mean-field formalism to calculate transport coefficients, allowing us to make quantitative predictions of the recombined fraction of point defects as a function of temperature and irradiation rate using homogeneous rate equations. We identify two different mechanisms according to which solutes lead to an increase in the recombined fraction of point defects; at low temperature, solutes slow down vacancies (kinetic effect), while at high temperature, solutes stabilize vacancies in the solid solution (thermodynamic effect). Extension to other metallic matrices and solutes are discussed.

Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, Martina E., E-mail: m.schmidt@dkfz.de; Meynköhn, Anna; Habermann, Nina

Purpose: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. Methods and Materials: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naïve participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research andmore » Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R{sup 2} effect-size measures for mediation were calculated. Results: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL-1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. Conclusions: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy

Fatal infection caused by a multiply resistant type 3 pneumococcus.

PubMed Central

Lawrenson, J B; Klugman, K P; Eidelman, J I; Wasas, A; Miller, S D; Lipman, J

1988-01-01

The most virulent pneumococcal serotype (type 3) has not to date been associated with multiple antimicrobial resistance. We report an unusual gastrointestinal presentation of fatal septicemia caused by a multiply resistant type 3 pneumococcus in a setting of increasing prevalence of multiple resistance, including resistance to erythromycin, clindamycin, and tetracycline. PMID:3170717

Radiation resistances and decontamination of common pathogenic bacteria contaminated in white scar oyster ( Crassostrea belcheri) in Thailand

NASA Astrophysics Data System (ADS)

Thupila, Nunticha; Ratana-arporn, Pattama; Wilaipun, Pongtep

2011-07-01

In Thailand, white scar oyster ( Crassostrea belcheri) was ranked for premium quality, being most expensive and of high demand. This oyster is often eaten raw, hence it may pose health hazards to consumers when contaminated with food-borne pathogens. As limited alternative methods are available to sterilize the oyster while preserving the raw characteristic, irradiation may be considered as an effective method for decontamination. In this study, the radiation resistance of pathogenic bacteria commonly contaminating the oyster and the optimum irradiation doses for sterilization of the most radiation resistant bacteria were investigated. The radiation decimal reduction doses ( D10) of Salmonella Weltevreden DMST 33380, Vibrio parahaemolyticus ATCC 17802 and Vibrio vulnificus DMST 5852 were determined in broth culture and inoculated oyster homogenate. The D10 values of S. Weltevreden, V. parahaemolyticus and V. vulnificus in broth culture were 0.154, 0.132 and 0.059 kGy, while those of inoculated oyster homogenate were 0.330, 0.159 and 0.140 kGy, respectively. It was found that among the pathogens tested, S. Weltevreden was proved to be the most resistant species. An irradiation dose of 1.5 kGy reduced the counts of 10 5 CFU/g S. Weltevreden inoculated in oyster meat to an undetectable level. The present study indicated that a low-dose irradiation can improve the microbial quality of oyster and further reduce the risks from the food-borne pathogens without adversely affecting the sensory attributes.

Rosiglitazone attenuates NF-{kappa}B-dependent ICAM-1 and TNF-{alpha} production caused by homocysteine via inhibiting ERK{sub 1/2}/p38MAPK activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Yong-Ping; Liu, Yu-Hui; Chen, Jia

2007-08-17

Previous studies demonstrated an important interaction between nuclear factor-kappaB (NF-{kappa}B) activation and homocysteine (Hcy)-induced cytokines expression in endothelial cells and vascular smooth muscle cells. However, the underlying mechanism remains illusive. In this study, we investigated the effects of Hcy on NF-{kappa}B-mediated sICAM-1, TNF-{alpha} production and the possible involvement of ERK{sub 1/2}/p38MAPK pathway. The effects of rosiglitazone intervention were also examined. Our results show that Hcy increased the levels of sICAM-1 and TNF-{alpha} in cultured human umbilical vein endothelial cells (HUVECs) in a time- and concentration-dependent manner. This effect was significantly depressed by rosiglitazone and different inhibitors (PDTC, NF-{kappa}B inhibitor; PD98059,more » MEK inhibitor; SB203580, p38MAPK specific inhibitor; and staurosporine, PKC inhibitor). Next, we investigated the effect of Hcy on ERK{sub 1/2}/p38MAPK pathway and NF-{kappa}B activity in HUVECs. The results show that Hcy activated both ERK{sub 1/2}/p38MAPK pathway and NF-{kappa}B-DNA-binding activity. These effects were markedly inhibited by rosiglitazone as well as other inhibitors (SB203580, PD98059, and PDTC). Further, the pretreatment of staurosporine abrogated ERK{sub 1/2}/p38MAPK phosphorylation, suggesting that Hcy-induced ERK{sub 1/2}/p38MAPK activation is associated with PKC activity. Our results provide evidence that Hcy-induced NF-{kappa}B activation was mediated by activation of ERK{sub 1/2}/p38MAPK pathway involving PKC activity. Rosiglitazone reduces the NF-{kappa}B-mediated sICAM-1 and TNF-{alpha} production induced by Hcy via inhibition of ERK{sub 1/2}/p38MAPK pa0011thw.« less

The 3D Radiation Dose Analysis For Satellite

NASA Astrophysics Data System (ADS)

Cai, Zhenbo; Lin, Guocheng; Chen, Guozhen; Liu, Xia

2002-01-01

hence, it is too simple to guide satellite radiation protection and ground experiments only based on the 1D radiation analysis results. To comprehend the radiation dose status of satellite adequately, it's essential to perform 3D radiation analysis for satellites. using computer software. From this 3D layout, the satellite model can be simplified appropriately. First select the point to be analyzed in the simplified satellite model, and extend many lines to the outside space, which divides the 4 space into many corresponding small areas with a certain solid angle. Then the shielding masses through the satellite equipment and structures along each direction are calculated, resulting in the shielding mass distribution in all space directions based on the satellite layout. Finally, using the relationship between radiation dose and shielding thickness from the 1D analysis, calculate the radiation dose in each area represented by each line. After we obtain the radiation dose and its space distribution for the point of interest, the 3D satellite radiation analysis is completed. radiation analysis based on satellite 3D CAD layout has larger benefit for engineering applications than the 1D analysis based on the solid sphere shielding model. With the 3D model, the analysis of space environment and its effect is combined closely with actual satellite engineering. The 3D radiation analysis not only provides valuable engineering data for satellite radiation design and protection, but also provides possibility to apply new radiation protection approaches, which expands technology horizon and broadens ways for technology development.

Reversal of dexamethasone induced insulin resistance in 3T3L1 adipocytes by 3β-taraxerol of Mangifera indica.

PubMed

Sangeetha, K N; Shilpa, K; Jyothi Kumari, P; Lakshmi, B S

2013-02-15

The present study investigates the efficacy of Mangifera indica ethyl acetate extract (MIEE) and its bioactive compound, 3β-taraxerol in the reversal of dexamethasone (DEX) induced insulin resistance in 3T3L1 adipocytes. MIEE and 3β-taraxerol were evaluated for their ability to restore impaired glucose uptake and, expression of molecular markers in the insulin signaling pathway induced by DEX in 3T3L1 adipocytes using 2-deoxy-D-[1-(3)H] glucose uptake assay and ELISA. An insulin resistant model has been developed using a glucocorticoid, DEX on 3T3L1 adipocytes. Insulin resistant condition was observed at 24h of DEX induction wherein a maximum degree of resistance of about 50% was measured based on inhibition of glucose uptake, which was confirmed using cytotoxicity analysis. The developed model of insulin resistance was studied in comparison to positive control rosiglitazone. DEX induced inhibition of glucose uptake and the expression of insulin signaling markers GLUT4 and PI3K were found to be restored by 3β-taraxerol and MIEE, thus delineating its mechanism of action in the reversal of insulin resistance. 3β-Taraxerol effectively restored DEX induced desensitization via restoration of PI3K and GLUT4 expression. To conclude, since 3β-taraxerol exhibits significant effect in reversing insulin resistance it can be further investigated as an insulin resistance reversal agent. Copyright © 2012 Elsevier GmbH. All rights reserved.

Differential intracellular calcium influx, nitric oxide production, ICAM-1 and IL8 expression in primary bovine endothelial cells exposed to nonesterified fatty acids.

PubMed

Loaiza, Anitsi; Carretta, María D; Taubert, Anja; Hermosilla, Carlos; Hidalgo, María A; Burgos, Rafael A

2016-02-25

Nonesterified fatty acids (NEFAs) are involved in proinflammatory processes in cattle, including in the increased expression of adhesion molecules in endothelial cells. However, the mechanisms underlying these effects are still unknown. The aim of this study was to assess the effects of NEFAs on the intracellular calcium (Ca(2+) i) influx, nitric oxide production, and ICAM-1 and IL-8 expression in primary bovine umbilical vein endothelial cells (BUVECs). Myristic (MA), palmitic (PA), stearic (SA), oleic (OA) and linoleic acid (LA) rapidly increased Ca(2+) i. The calcium response to all tested NEFAs showed an extracellular calcium dependence and only the LA response was significantly inhibited until the intracellular calcium was chelated. The EC50 values for MA and LA were 125 μM and 37 μM, respectively, and the MA and LA effects were dependent on calcium release from the endoplasmic reticulum stores and on the L-type calcium channels. Only the calcium response to MA was significantly reduced by GW1100, a selective G-protein-coupled free fatty acid receptor (GPR40) antagonist. We also detected a functional FFAR1/GPR40 protein in BUVECs by using western blotting and the FFAR1/GPR40 agonist TAK-875. Only LA increased the cellular nitric oxide levels in a calcium-dependent manner. LA stimulation but not MA stimulation increased ICAM-1 and IL-8-expression in BUVECs. This effect was inhibited by GW1100, an antagonist of FFAR1/GPR40, but not by U-73122, a phospholipase C inhibitor. These findings strongly suggest that each individual NEFA stimulates endothelial cells in a different way, with clearly different effects on intracellular calcium mobilization, NO production, and IL-8 and ICAM-1 expression in primary BUVECs. These findings not only extend our understanding of NEFA-mediated diseases in ruminants, but also provide new insight into the different molecular mechanisms involved during endothelial cell activation by NEFAs.

Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization.

PubMed

Lau, Christine; Wang, Xiaomin; Song, Lihua; North, Michelle; Wiehler, Shahina; Proud, David; Chow, Chung-Wai

2008-01-15

Human rhinovirus (HRV) causes the common cold. The most common acute infection in humans, HRV is a leading cause of exacerbations of asthma and chronic obstruction pulmonary disease because of its ability to exacerbate airway inflammation by altering epithelial cell biology upon binding to its receptor, ICAM-1. ICAM-1 regulates not only viral entry and replication but also signaling pathways that lead to inflammatory mediator production. We recently demonstrated the Syk tyrosine kinase to be an important mediator of HRV-ICAM-1 signaling: Syk regulates replication-independent p38 MAPK activation and IL-8 expression. In leukocytes, Syk regulates receptor-mediated internalization via PI3K. Although PI3K has been shown to regulate HRV-induced IL-8 expression and clathrin-mediated endocytosis of HRV, the role of airway epithelial Syk in this signaling pathway is not known. We postulated that Syk regulates PI3K activation and HRV endocytosis in the airway epithelium. Using confocal microscopy and immunoprecipitation, we demonstrated recruitment of the normally cytosolic Syk to the plasma membrane upon HRV16-ICAM-1 binding, along with Syk-clathrin coassociation. Subsequent incubation at 37 degrees C to permit internalization revealed redistribution of Syk to punctate structures resembling endosomes and colocalization with HRV16. Internalized HRV was not detected in cells overexpressing the kinase inactive Syk(K396R) mutant, indicating that kinase activity was necessary for endocytosis. HRV-induced PI3K activation was dependent on Syk; Syk knockdown by small interfering RNA significantly decreased phosphorylation of the PI3K substrate Akt. Together, these data reveal Syk to be an important mediator of HRV endocytosis and HRV-induced PI3K activation.

Antimicrobial activity of silver nanoparticles synthesized using honey and gamma radiation against silver-resistant bacteria from wounds and burns

NASA Astrophysics Data System (ADS)

Hosny, A. M. S.; Kashef, M. T.; Rasmy, S. A.; Aboul-Magd, D. S.; El-Bazza, Z. E.

2017-12-01

Silver nanoparticles (AgNPs) are promising antimicrobial agents for treatment of wounds and burns. We synthesized AgNPs using honey at different pH values or with different gamma irradiation doses. The resulting nanoparticles were characterized by UV-vis spectroscopy, TEM, DLS and FTIR. Their antimicrobial activity, against standard bacterial strains and silver-resistant clinical isolates from infected wounds and burns, was evaluated in vitro through determination of their minimum inhibitory concentration (MIC). AgNPs prepared using 30 g of honey exposed to 5 kGy gamma radiation had the best physical characters regarding stability and uniformity of particle size and shape. They recorded the lowest MIC values against both the standard and silver-resistant isolates. In conclusion, honey and gamma radiation can be used in synthesis of highly stable pure AgNPs, without affecting the physico-chemical and antimicrobial activity of honey. This offered an advantage in terms of inhibition of silver-resistant bacteria isolates.

Resistance of the Extreme Halophile Halobacterium sp. NRC-1 to Multiple Stresses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gygli, Patrick E.; Prajapati, Surendra; DeVeaux, Linda C.

2009-03-10

The model Archaeon Halobacterium sp. NRC-1 is an extreme halophile known for its resistance to multiple stressors, including electron-beam and ultraviolet radiation. It is a well-developed system with a completely sequenced genome and extensive post-genomic tools for the study of a variety of biological processes. To further understand the mechanisms of Halobacterium's, radiation resistance, we previously reported the selection for multiple independent highly resistant mutants using repeated exposure to high doses of 18-20 MeV electrons using a medical S-band Linac. Molecular analysis of the transcriptional profile of several of these mutants revealed a single common change: upregulation of the rfa3more » operon. These genes encode proteins homologous to the subunits of eukaryotic Replication Protein A (RPA), a DNA binding protein with major roles in DNA replication, recombination, and repair. This operon has also been implicated in a somewhat lesser role in resistance of wild type Halobacterium to ultraviolet radiation, suggesting common mechanisms for resistance. To further understand the mechanism of radiation resistance in the mutant strains, we measured the survival after exposure to both electron-beam and ultraviolet radiation, UV-A, B, and C All mutant strains showed increased resistance to electrons when compared with the parent. However, the mutant strains do not display increased UV resistance, and in one case is more sensitive than the parent strain. Thus, the protective role of increased RPA expression within a cell may be specific to the DNA damage caused by the different physical effects induced by high energy electron-beam radiation.« less

NEAMS-ATF M3 Milestone Report: Literature Review of Modeling of Radiation-Induced Swelling in Fe-Cr-Al Steels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Xianming; Biner, Suleyman Bulent; Jiang, Chao

2015-12-01

Fe-Cr-Al steels are proposed as accident-tolerant-fuel (ATF) cladding materials in light water reactors due to their excellent oxidation resistance at high temperatures. Currently, the understanding of their performance in reactor environment is still limited. In this review, firstly we reviewed the experimental studies of Fe-Cr-Al based alloys with particular focus on the radiation effects in these alloys. Although limited data are available in literature, several previous and recent experimental studies have shown that Fe-Cr-Al based alloys have very good void swelling resistance at low and moderate irradiation doses but the growth of dislocation loops is very active. Overall, the behaviormore » of radiation damage evolution is similar to that in Fe-Cr ferritic/martensitic alloys. Secondly, we reviewed the rate theory-based modeling methods for modeling the coevolution of voids and dislocation loops in materials under irradiation such as Frenkel pair three-dimensional diffusion model (FP3DM) and cluster dynamics. Finally, we summarized and discussed our review and proposed our future plans for modeling radiation damage in Fe-Cr-Al based alloys.« less

Diffuse Reflectance Spectroscopy (DRS) of radiation-induced re-oxygenation in sensitive and resistant head and neck tumor xenografts

NASA Astrophysics Data System (ADS)

Dadgar, Sina; Rodríguez Troncoso, Joel; Rajaram, Narasimhan

2018-02-01

Currently, anatomical assessment of tumor volume performed several weeks after completion of treatment is the clinical standard to determine whether a cancer patient has responded to a treatment. However, functional changes within the tumor could potentially provide information regarding treatment resistance or response much earlier than anatomical changes. We have used diffuse reflectance spectroscopy to assess the short and long-term re-oxygenation kinetics of a human head and neck squamous cell carcinoma xenografts in response to radiation therapy. First, we injected UM-SCC-22B cell line into the flank of 50 mice to grow xenografts. Once the tumor volume reached 200 mm3 (designated as Day 1), the mice were distributed into radiation and control groups. Members of radiation group underwent a clinical dose of radiation of 2 Gy/day on Days 1, 4, 7, and 10 for a cumulative dose of 8 Gy. DRS spectra of these tumors were collected for 14 days during and after therapy, and the collected spectra of each tumor were converted to its optical properties using a lookup table-base inverse model. We found statistically significant differences in tumor growth rate between two groups which is in indication of the sensitivity of this cell line to radiation. We further acquired significantly different contents of hemoglobin and scattering magnitude and size in two groups. The scattering has previously been associated with necrosis. We furthermore found significantly different time-dependent changes in vascular oxygenation and tumor hemoglobin concentration in post-radiation days.

Combination therapeutics of Nilotinib and radiation in acute lymphoblastic leukemia as an effective method against drug-resistance.

PubMed

Kaveh, Kamran; Takahashi, Yutaka; Farrar, Michael A; Storme, Guy; Guido, Marcucci; Piepenburg, Jamie; Penning, Jackson; Foo, Jasmine; Leder, Kevin Z; Hui, Susanta K

2017-07-01

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI) therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR) in combination with TKI therapy overcome chemo-resistance. Additionally, we developed a mathematical model, parameterized by cell viability experiments under Nilotinib treatment and LDR, to explain the cellular response to combination therapy. The addition of LDR significantly reduced drug resistance both in vitro and in computational model. Decreased expression level of phosphorylated AKT suggests that the combination treatment plays an important role in overcoming resistance through the AKT pathway. Model-predicted cellular responses to the combined therapy provide good agreement with experimental results. Augmentation of LDR and Nilotinib therapy seems to be beneficial to control Ph+ leukemia resistance and the quantitative model can determine optimal dosing schedule to enhance the effectiveness of the combination therapy.

ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease.

PubMed

Barresi, Vincenza; Signorelli, Salvatore S; Musso, Nicolò; Anzaldi, Massimiliano; Fiore, Valerio; Alberghina, Mario; Condorelli, Daniele Filippo

2014-06-01

The genotype distribution of two gene polymorphisms, previously associated with peripheral artery disease (PAD), has been evaluated in a population of diabetic (DPAD) and non-diabetic (NDPAD) patients affected by symptomatic PAD (stages II-IV). A decreased frequency of the AA genotype of rs5498 (ICAM-1) was observed in the PAD subjects compared to controls but this result did not reach statistical significance (p=0.06 by chi-squared test). On the contrary, a significant increase in the frequency of the GG homozygous genotype of rs248793 (SRD5A1) was observed in the PAD patient group in comparison to controls (p=0.01). These data confirm that the GG genotype of rs248793 in the SRD5A1 gene is significantly associated with symptomatic PAD and show a trend towards a stronger association with the non-diabetic status. © The Author(s) 2014.

Multitemporal and Multiscaled Fractal Analysis of Landsat Satellite Data Using the Image Characterization and Modeling System (ICAMS)

NASA Technical Reports Server (NTRS)

Quattrochi, Dale A.; Emerson, Charles W.; Lam, Nina Siu-Ngan; Laymon, Charles A.

1997-01-01

The Image Characterization And Modeling System (ICAMS) is a public domain software package that is designed to provide scientists with innovative spatial analytical tools to visualize, measure, and characterize landscape patterns so that environmental conditions or processes can be assessed and monitored more effectively. In this study ICAMS has been used to evaluate how changes in fractal dimension, as a landscape characterization index, and resolution, are related to differences in Landsat images collected at different dates for the same area. Landsat Thematic Mapper (TM) data obtained in May and August 1993 over a portion of the Great Basin Desert in eastern Nevada were used for analysis. These data represent contrasting periods of peak "green-up" and "dry-down" for the study area. The TM data sets were converted into Normalized Difference Vegetation Index (NDVI) images to expedite analysis of differences in fractal dimension between the two dates. These NDVI images were also resampled to resolutions of 60, 120, 240, 480, and 960 meters from the original 30 meter pixel size, to permit an assessment of how fractal dimension varies with spatial resolution. Tests of fractal dimension for two dates at various pixel resolutions show that the D values in the August image become increasingly more complex as pixel size increases to 480 meters. The D values in the May image show an even more complex relationship to pixel size than that expressed in the August image. Fractal dimension for a difference image computed for the May and August dates increase with pixel size up to a resolution of 120 meters, and then decline with increasing pixel size. This means that the greatest complexity in the difference images occur around a resolution of 120 meters, which is analogous to the operational domain of changes in vegetation and snow cover that constitute differences between the two dates.

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

PubMed

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma

PubMed Central

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor. PMID:24817962

A novel immune resistance mechanism of melanoma cells controlled by the ADAR1 enzyme

PubMed Central

Galore-Haskel, Gilli; Nemlich, Yael; Greenberg, Eyal; Ashkenazi, Shira; Hakim, Motti; Itzhaki, Orit; Shoshani, Noa; Shapira-Fromer, Ronnie; Ben-Ami, Eytan; Ofek, Efrat; Anafi, Liat; Besser, Michal J.

2015-01-01

The blossom of immunotherapy in melanoma highlights the need to delineate mechanisms of immune resistance. Recently, we have demonstrated that the RNA editing protein, adenosine deaminase acting on RNA-1 (ADAR1) is down-regulated during metastatic transition of melanoma, which enhances melanoma cell proliferation and tumorigenicity. Here we investigate the role of ADAR1 in melanoma immune resistance. Importantly, knockdown of ADAR1 in human melanoma cells induces resistance to tumor infiltrating lymphocytes in a cell contact-dependent mechanism. We show that ADAR1, in an editing-independent manner, regulates the biogenesis of miR-222 at the transcription level and thereby Intercellular Adhesion Molecule 1 (ICAM1) expression, which consequently affects melanoma immune resistance. ADAR1 thus has a novel, pivotal, role in cancer immune resistance. Corroborating with these results, the expression of miR-222 in melanoma tissue specimens was significantly higher in patients who had no clinical benefit from treatment with ipilimumab as compared to patients that responded clinically, suggesting that miR-222 could function as a biomarker for the prediction of response to ipilimumab. These results provide not only novel insights on melanoma immune resistance, but also pave the way to the development of innovative personalized tools to enable optimal drug selection and treatment. PMID:26338962

FlexyDos3D: a deformable anthropomorphic 3D radiation dosimeter: radiation properties

NASA Astrophysics Data System (ADS)

De Deene, Y.; Skyt, P. S.; Hil, R.; Booth, J. T.

2015-02-01

Three dimensional radiation dosimetry has received growing interest with the implementation of highly conformal radiotherapy treatments. The radiotherapy community faces new challenges with the commissioning of image guided and image gated radiotherapy treatments (IGRT) and deformable image registration software. A new three dimensional anthropomorphically shaped flexible dosimeter, further called ‘FlexyDos3D’, has been constructed and a new fast optical scanning method has been implemented that enables scanning of irregular shaped dosimeters. The FlexyDos3D phantom can be actuated and deformed during the actual treatment. FlexyDos3D offers the additional advantage that it is easy to fabricate, is non-toxic and can be molded in an arbitrary shape with high geometrical precision. The dosimeter formulation has been optimized in terms of dose sensitivity. The influence of the casting material and oxygen concentration has also been investigated. The radiophysical properties of this new dosimeter are discussed including stability, spatial integrity, temperature dependence of the dosimeter during radiation, readout and storage, dose rate dependence and tissue equivalence. The first authors Y De Deene and P S Skyt made an equivalent contribution to the experimental work presented in this paper.

Effect of Korean Red Ginseng on radiation-induced bone loss in C3H/HeN mice

PubMed Central

Lee, Jin-Hee; Lee, Hae-June; Yang, Miyoung; Moon, Changjong; Kim, Jong-Choon; Bae, Chun-Sik; Jo, Sung-Kee; Jang, Jong-Sik; Kim, Sung-Ho

2013-01-01

This study investigated the effects of Korean Red Ginseng (KRG) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham and irradiation (3 Gy, gamma-ray) groups. The irradiated mice were treated for 12 wk with vehicle, KRG (per os, p.o.) or KRG (intraperitoneal). Serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase, estradiol level, and biomechanical properties were measured. Tibiae were analyzed using micro-computed tomography. Treatment of KRG (p.o., 250 mg/kg of body weight/d) significantly preserved trabecular bone volume, trabecular number, structure model index, and bone mineral density of proximal tibia metaphysic, but did not alter the uterus weight of the mice. Serum ALP level was slightly reduced by KRG treatment. However, grip strength, mechanical property, and cortical bone architecture did not differ among the experimental groups. The results indicate that KRG can prevent radiation-induced bone loss in mice. PMID:24233384

Radiation survival of two nalidixic acid resistant strains of Salmonella typhimurium in various media

NASA Astrophysics Data System (ADS)

Shamsuzzaman, Kazi; Goodwin, Marlene; George, Ian; Singh, Harwant

Radiation doses required for 90% inactivation, the D10 values, have been determined for two nalidixic acid-resistant strains of Salmonella typhimurium, Nal R ATCC 13311 and K1-2B, in different media. The D10 values were 0.20, 0.57 and 0.53 kGy for the ATCC 13311 strain, and were 0.21, 0.4 and 0.32 kGy for the K1-2B strain, in phosphate buffer, in nutrient broth and on chicken drumsticks, respectively. Since these two strains have radiation sensitivity similar to several Salmonella serotypes reported in the literature, they are good indicator organisms for use in studies on the effect of irradiation on Salmonella in foods that might frequently be contaminated with such organisms.

Molecular imaging biomarkers of resistance to radiation therapy for spontaneous nasal tumors in canines.

PubMed

Bradshaw, Tyler J; Bowen, Stephen R; Deveau, Michael A; Kubicek, Lyndsay; White, Pamela; Bentzen, Søren M; Chappell, Richard J; Forrest, Lisa J; Jeraj, Robert

2015-03-15

Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV(max); SUV(mean)) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R(2). The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV(mean) (P=.018), and midtreatment FLT SUV(max) (P=.006). Large decreases in FLT SUV(mean) from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV(max) (P=.022) in combination with large FLT response from pretreatment to midtreatment (P=.041

The Competing Influences of the Radiation Belts on the Charging of Extremely Resistive Spacecraft Materials

NASA Astrophysics Data System (ADS)

Lemon, C.; Roeder, J. L.; Looper, M. D.; O'Brien, T. P., III; Fennell, J. F.; Mazur, J. E.

2016-12-01

Spacecraft suffer from various types of anomalies caused by space weather. One important source of spacecraft anomalies is internal electrostatic discharge (IESD), which occurs when penetrating electrons deposit charge inside dielectrics faster than that charge can dissipate via conduction currents. This causes the electric field to build up to a breakdown threshold. The most electrically resistive materials, such as Teflon, are of greatest concern for IESD. Laboratory measurements of the conductivity of Teflon and other highly resistive polymers show that their conventional conductivity is negligible in comparison to their radiation-induced conductivity (RIC), an alternate source of conduction that is linearly proportional to the ionizing dose rate received by the material. The space radiation environment therefore plays contradictory roles in extremely resistive polymers, both depositing charge and dissipating it. The spectral shape, rather than the total electron flux, becomes the primary consideration for IESD because it determines the relative deposition of charge and ionizing dose in materials. A counterintuitive result is that soft spectra may be a greater risk for IESD, because relative to hard spectra they deposit more charge than dose in materials. This differs from the standard practice of defining the worst-possible environment for charging and IESD as the spectrum in which the electron flux is highest at all energies that could reach the material. We present analyses of CRRES MEA and HEEF measurements, and simulate the charging of material samples from the CRRES Internal Discharge Monitor. We briefly demonstrate the unexpected results described here, and quantify the effect of different energetic electron spectra observed by CRRES on the buildup of charge in Teflon samples from the Internal Discharge Monitor. Finally, we will comment on the perceived deficiency of "worst case" charging environments for predicting IESD, and how we can better quantify

Reduced H3K27me3 expression in radiation-associated angiosarcoma of the breast.

PubMed

Mentzel, Thomas; Kiss, Katalin

2018-03-01

The diagnosis of radiation-associated angiosarcoma is challenging and there are overlapping clinicopathological features between radiation-associated benign, atypical and malignant vascular lesions. It has been shown convincingly, that the majority of radiation-associated angiosarcomas are characterised by amplification and subsequent overexpression of MYC in contrast to benign and atypical vascular lesions. Given the fact that epigenetic changes play an important role in carcinogenesis and loss of histone H3K27 trimethylation (H3K27me3) has been found in a number of malignant neoplasms including malignant peripheral nerve sheath tumours, especially when associated with previous radiotherapy, we evaluated the immunohistochemical reaction pattern for H3K27me3 in 49 vascular lesions and control cases: normal skin and benign vascular lesions not associated with previous radiotherapy, radiation-associated benign, atypical and malignant vascular lesions and angiosarcomas not associated with previous radiotherapy. We found loss of H3K27me3 expression in most cases of radiation-associated angiosarcomas, whereas endothelial cells in benign and atypical vascular lesions arising after previous radiotherapy stained positively for H3K27me3. The sporadic angiosarcomas stained inconsistently for H3K27me3. Loss of H3K27me3 is typically seen in radiation-associated angiosarcomas, representing an additional diagnostic tool and raises questions in regard to the carcinogenesis of malignant vascular neoplasms.

Thermal resistance, tensile properties, and gamma radiation shielding performance of unsaturated polyester/nanoclay/PbO composites

NASA Astrophysics Data System (ADS)

Bagheri, Kobra; Razavi, Seyed Mohammad; Ahmadi, Seyed Javad; Kosari, Mohammadreza; Abolghasemi, Hossein

2018-05-01

Composites of unsaturated polyester containing 5 wt% nanoclay and different amounts of lead monoxide particles (0, 10, 20, and 30 wt%) were prepared. XRD patterns showed the exfoliation of nanoclay layers in the polymer. Morphological properties of the composites were studied using SEM micrographs. The prepared composites were investigated for their thermal resistance and mechanical properties using thermogravimetric analysis and tensile testing method, respectively. Addition of lead monoxide to the polymer worsened its thermal resistance and tensile properties, whereas the observed negative effects could be moderated by the clay nanoparticle. Gamma attenuation performance of the composites was evaluated by 192Ir, 137Cs, and 60Co gamma radiation sources. Linear attenuation coefficient and mass attenuation coefficient of the composites were found to be increased with the increase of PbO content. Shielding efficiency of the prepared composites was compared with some conventional shielding materials regarding their half value layer thickness. UP/nanoclay/PbO composites were found to be suitable materials for the low-energy gamma radiation shielding applications.

Effects of gamma irradiation on the radiation-resistant bacteria and polyphenol oxidase activity in fresh kale juice

NASA Astrophysics Data System (ADS)

Kim, Dongho; Song, Hyunpa; Lim, Sangyong; Yun, Hyejeong; Chung, Jinwoo

2007-07-01

Gamma radiation was performed to prolong the shelf life of natural kale juice. The total aerobic bacteria in fresh kale juice, prepared by a general kitchen process, was detected in the range of 10 6 cfu/ml, and about 10 2 cfu/ml of the bacteria survived in the juice in spite of gamma irradiation treatment with a dose of 5 kGy. Two typical radiation-resistant bacteria, Bacillus megaterium and Exiguobacterium acetylicum were isolated and identified from the 5 kGy-irradiated kale juices. The D10 values of the vegetative cell and endospore of the B. megaterium in peptone water were 0.63±0.05 and 1.52±0.05 kGy, respectively. The D10 value of the E. acetylicum was calculated as 0.65±0.06 kGy. In the inoculation test, the growth of the surviving B. megaterium and E. acetylicum in the 3-5 kGy-irradiated kale juice retarded and/or decreased significantly during a 3 d post-irradiation storage period. However, there were no significant differences in the residual polyphenol oxidase activity and browning index between the nonirradiated control and the gamma irradiated kale juice during a post-irradiation period.

Time-dependent expression of ICAM-1 & VCAM-1 on coronaries of the heterotopically transplanted mouse heart.

PubMed Central

Lee, J. R.; Huh, J. H.; Seo, J. W.; Suk, C. J.; Jeong, H. M.; Kim, E. K.

1999-01-01

To investigate the pathogenesis of accelerated graft atherosclerosis after cardiac transplantation, a genetically well-defined and reproducible animal model is required. We performed heterotopic intraabdominal heart transplantation between the two inbred strains of mice. Forty hearts from B10.A mice were transplanted into B10.BR mice. Recipients were sacrificed at 1, 3, 5, 7, 14, 28, and 42 days after implantation. The specimens from both donor and recipient were examined with fluorescent immunohistochemistry and the serial histopathologic changes were evaluated. In the donor hearts, ICAM-1 and VCAM-1 expressions were minimal at day 1 and they gradually increased, reaching their peaks on day 5 or 7 and remained unchanged by day 42. However, there were very little expressions in the recipients' hearts. Mean percent areas of intima in the donor coronaries revealed progressive increase by day 42. However, those in the recipients occupied consistently less than 5% of the lumen. In conclusion, we demonstrated that a heterotopic murine heart transplantation model was a useful tool to produce transplantation coronary artery disease and that adhesion molecules on the cardiac allografts were activated very early and remained elevated at all time-points, nonetheless the arterial lesion was detected after day 28 and its progression was accelerated thereafter. PMID:10402165

Radiation Resistance Studies of Amorphous Silicon Alloy Photovoltaic Materials

NASA Technical Reports Server (NTRS)

Woodyard, James R.

1994-01-01

The radiation resistance of commercial solar cells fabricated from hydrogenated amorphous silicon alloys was investigated. A number of different device structures were irradiated with 1.0 MeV protons. The cells were insensitive to proton fluences below 1E12 sq cm. The parameters of the irradiated cells were restored with annealing at 200 C. The annealing time was dependent on proton fluence. Annealing devices for one hour restores cell parameters for fluences below lE14 sq cm require longer annealing times. A parametric fitting model was used to characterize current mechanisms observed in dark I-V measurements. The current mechanisms were explored with irradiation fluence, and voltage and light soaking times. The thermal generation current density and quality factor increased with proton fluence. Device simulation shows the degradation in cell characteristics may be explained by the reduction of the electric field in the intrinsic layer.

Radiation Resistances of Dielectric Liquids

NASA Technical Reports Server (NTRS)

Bouquet, Frank L.; Somoano, Robert B.

1987-01-01

Report presents data on effects of ionizing radiation on dielectric liquids for high-energy-density, pulsed-power capacitors. Based on Jet Propulsion Laboratory test results, search of NASA and Department of Energy computer files, survey of open literature, and contacts with manufacturers and suppliers. Covers 22 organic liquids, although detailed data found for only one compound, polydimethyl siloxane. Generic data on effects of radiation on compounds with similar chemical structures provided where data on specific compounds lacking.

Epoxy-borax-coal tar composition for a radiation protective, burn resistant drum liner and centrifugal casting method

DOEpatents

Taylor, Robert S.; Boyer, Norman W.

1980-01-01

A boron containing burn resistant, low level radiation protection material useful, for example, as a liner for radioactive waste disposal and storage, a component for neutron absorber, and a shield for a neutron source. The material is basically composed of Borax in the range of 25-50%, coal tar in the range of 25-37.5%, with the remainder being an epoxy resin mix. A preferred composition is 50% Borax, 25% coal tar and 25% epoxy resin. The material is not susceptible to burning and is about 1/5 the cost of existing radiation protection material utilized in similar applications.

Epoxy-borax-coal tar composition for a radiation protective, burn resistant drum liner and centrifugal casting method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyer, N.W.; Taylor, R.S.

1980-10-28

A boron containing burn resistant, low level radiation protection material useful, for example, as a liner for radioactive waste disposal and storage, a component for neutron absorber, and a shield for a neutron source. The material is basically composed of borax in the range of 25-50%, coal tar in the range of 25-37.5%, with the remainder being an epoxy resin mix. A preferred composition is 50% borax, 25% coal tar and 25% epoxy resin. The material is not susceptible to burning and is about 1/5 the cost of existing radiation protection material utilized in similar applications.

LDR reverses DDP resistance in ovarian cancer cells by affecting ERCC-1, Bcl-2, Survivin and Caspase-3 expressions.

PubMed

Ju, Xingyan; Yu, Hongsheng; Liang, Donghai; Jiang, Tao; Liu, Yuanwei; Chen, Ling; Dong, Qing; Liu, Xiaoran

2018-06-01

Ovarian cancer is the most frequent cause of death resulting from malignant gynecological tumors. After surgical intervention, cisplatin (DDP) is a major chemotherapy drug for ovarian cancer, but the ovarian cancer cells tend to develop DDP resistance in the clinical setting. Tumor cells are sensitive to low-dose radiation (LDR). However, how the LDR therapy improves the effects of chemotherapy drugs on ovarian cancer is not well understood. This study aimed to explore this issue. The SKOV3/DDP cells were divided into 3 groups, including low-dose group, conventional-dose group, and control group (no radiation). Cell counting kit-8 assay was performed to measure cell proliferation. Flow cytometric analysis was then utilized to quantify the apoptosis with classical Annexin V/propidium iodide co-staining. And Real-time quantitative PCR and western blot were eventually used to analyze the mRNA and protein levels of excision repair cross complementing-group 1 (ERCC1), B-cell lymphoma 2 (Bcl-2), Survivin and Caspase-3, respectively. The IC50 value of DDP in the low-dose group was significantly lower compared with the other two groups. Compared with the conventional-dose group and control group, LDR treatment resulted in significantly more apoptosis. Besides, LDR treatment significantly decreased the mRNA and protein expression of ERCC1, Bcl-2, and Survivin, and enhanced the mRNA and protein expression of Caspase-3 compared with the other two groups. LDR reversed DDP resistance in SKOV3/DDP cells possibly by suppressing ERCC1, Bcl-2, and Survivin expressions, and increasing Caspase-3 expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

F2 screen, inheritance and cross-resistance of field-derived Vip3A resistance in Spodoptera frugiperda (Lepidoptera: Noctuidae) collected from Louisiana, USA.

PubMed

Yang, Fei; Morsello, Shannon; Head, Graham P; Sansone, Chris; Huang, Fangneng; Gilreath, Ryan T; Kerns, David L

2017-11-28

Fall armyworm, Spodoptera frugiperda, is a target pest of the Vip3A protein used in pyramided Bt corn and cotton in the USA. In this study, we provide the first documentation of a resistance allele conferring Vip3A resistance in a field-derived population of S. frugiperda from the USA, and characterize its inheritance and cross-resistance. An F 2 screen with 104 two-parent families generated from a field collection of S. frugiperda in Louisiana, USA, resulted in one family carrying a Vip3A resistance allele. The Vip3A-resistant strain (RR) derived from the two-parent family showed a high level of resistance to Vip3A in both diet and whole-plant bioassays, with a resistance ratio of >632.0-fold relative to a susceptible population (SS) based on diet-overlay bioassays. The inheritance of Vip3A resistance was monogenic, autosomal and recessive. Furthermore, the Vip3A resistance conferred no cross-resistance to Cry1F, Cry2Ab2 or Cry2Ae purified proteins, with resistance ratios of 3.5, 5.0 and 1.1, respectively. These findings provide valuable information for characterizing Vip3A resistance, resistance monitoring, and developing effective resistance management strategies for the sustainable use of the Vip3A technology. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Radiation resistance of non-0157:H7 Shiga Toxin-Producing Escherichia coli suspended in refrigerated catfish fillet meat

USDA-ARS?s Scientific Manuscript database

Ionization (gamma) irradiation is a sustainable and important non-thermal treatment that has been very effective in controlling microorganisms and improving the safety and shelf life of foods. In the design of the food irradiation process, the knowledge of the radiation resistance of the target orga...

Radiation-Induced Astrogliosis and Blood-Brain Barrier Damage Can Be Abrogated Using Anti-TNF Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Christy M.; Gaber, M. Waleed; Sabek, Omaima M.

2009-07-01

Purpose: In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors. Methods and Materials: Intravital microscopy and a closed cranial window technique were used to measure quantitatively BBB permeability to FITC-dextran 4.4-kDa molecules, leukocyte adhesion (Rhodamine-6G) and vessel diameters before and after 20-Gy cranial radiation with and without treatment with anti-TNF. Immunohistochemistry was used to quantify astrogliosis post-RT and immunofluorescence was used to visualize protein expression of TNF and ICAM-1 post-RT. Recombinant TNF (rTNF) was used to elucidatemore » the role of TNF in leukocyte adhesion and vessel diameter. Results: Mice treated with anti-TNF showed significantly lower permeability and leukocyte adhesion at 24 and 48 h post-RT vs. RT-only animals. We observed a significant decrease in arteriole diameters at 48 h post-RT that was inhibited in TNF-treated animals. We also saw a significant increase in activated astrocytes following RT that was significantly lower in the anti-TNF-treated group. In addition, immunofluorescence showed protein expression of TNF and ICAM-1 in the cerebral cortex that was inhibited with anti-TNF treatment. Finally, administration of rTNF induced a decrease in arteriole diameter and a significant increase in leukocyte adhesion in venules and arterioles. Conclusions: TNF plays a significant role in acute changes in BBB permeability, leukocyte adhesion, arteriole diameter, and astrocyte activation following cranial radiation. Treatment with anti-TNF protects the brain's microvascular network from the acute damage following RT.« less

Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase

PubMed Central

Victor, Victor M.; Rovira-Llopis, Susana; Bañuls, Celia; Diaz-Morales, Noelia; Martinez de Marañon, Arantxa; Rios-Navarro, Cesar; Alvarez, Angeles; Gomez, Marcelino; Rocha, Milagros; Hernández-Mijares, Antonio

2016-01-01

Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E-selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR. PMID:27007571

Mercury Chalcohalide Semiconductor Hg 3Se 2Br 2 for Hard Radiation Detection

DOE PAGES

Li, Hao; Meng, Fang; Malliakas, Christos D.; ...

2016-09-28

We present Hg 3Se 2Br 2 that has a wide band gap semiconductor (2.22 eV) with high density (7.598 g/cm 3) and crystallizes in the monoclinic space group C2/m with cell parameters of a = 17.496 (4) Å, b = 9.3991 (19) Å, c = 9.776(2) Å, β = 90.46(3)°, V = 1607.6(6) Å 3. It melts congruently at a low temperature, 566°C, which allows for an easy single crystal growth directly from the stoichiometric melt. Single crystals of Hg 3Se 2Br 2 up to 1 cm long have been grown using the Bridgman method. Hg 3Se 2Br 2 singlemore » crystals exhibit a strong photocurrent response when exposed to Ag X-ray and blue diode laser. The resistivity of Hg 3Se 2Br 2 measured by the two probe method is on the order of 10 11 Ω·cm, and the mobility-lifetime product (μτ) of the electron and hole carriers estimated from the energy spectroscopy under Ag X-ray radiation are (μτ) e ≈ 1.4 × 10 –4cm 2/V and (μτ) h ≈ 9.2 × 10 –5cm 2/V. Electronic structure calculations at the density functional theory level indicate a direct band gap and a relatively small effective mass for carriers. Lastly, on the basis of the photoconductivity and hard X-ray spectrum, Hg 3Se 2Br 2 is a promising candidate for X-ray and γ-ray radiation detection at room temperature.« less

Highly osteogenic PDL stem cell clones specifically express elevated levels of ICAM1, ITGB1 and TERT.

PubMed

Sununliganon, Laddawun; Singhatanadgit, Weerachai

2012-01-01

Cells derived from the periodontal ligament (PDL) have previously been reported to have stem cell-like characteristics (PDL stem cells; PDLSCs) and play an important part in bone engineering, including that of alveolar bone. However, these populations have been heterogeneous, and thus far no specific marker has yet been established from adult human stem cells derived from PDL tissue. We have previously isolated highly purified single cell-derived PDLSC clones and delineated their phenotypic and functional characteristics. In this report, we further obtained three homogeneous and distinct PDLSC clones demonstrating low, moderate and high mineralized matrix forming ability-namely PC12, PC4 and PC3, respectively, and the expression of mesenchymal stem cell pathway-specific genes in these clones was investigated. PCR array revealed that the expression of intercellular adhesion molecule 1 (ICAM1), integrin beta 1 (ITGB1) and telomerase reverse transcriptase (TERT) was associated with highly osteogenic PDLSC clones, as determined by the expression of key osteoblastic markers and their ability to form alizarin red S positive mineralized matrix in vitro. The present results suggest that these three mesenchymal stem cell-associated markers could potentially be used to isolate PDLSCs with high osteogenic capability for engineering new bone.

Plasma protein binding of an antisense oligonucleotide targeting human ICAM-1 (ISIS 2302).

PubMed

Watanabe, Tanya A; Geary, Richard S; Levin, Arthur A

2006-01-01

In vitro ultrafiltration was used to determine the plasma protein-binding characteristics of phosphorothioate oligonucleotides (PS ODNs). Although there are binding data on multiple PS ODNs presented here, the focus of this research is on the protein-binding characteristics of ISIS 2302, a PS ODN targeting human intercellular adhesion molecule-1 (ICAM-1) mRNA, which is currently in clinical trials for the treatment of ulcerative colitis. ISIS 2302 was shown to be highly bound (> 97%) across species (mouse, rat, monkey, human), with the mouse having the least degree of binding. ISIS 2302 was highly bound to albumin and, to a lesser, extent alpha2-macroglobulin and had negligible binding to alpha1-acid glycoprotein. Ten shortened ODN metabolites (8, 10, and 12-19 nucleotides [nt] in length, truncated from the 3' end) were evaluated in human plasma. The degree of binding was reduced as the ODN metabolite length decreased. Three additional 20-nt (20-mer) PS ODNs (ISIS 3521, ISIS 2503, and ISIS 5132) of varying sequence but similar chemistry were evaluated. Although the tested PS ODNs were highly bound to plasma proteins, suggesting a commonality within the chemical class, these results suggested that the protein-binding characteristics in human plasma may be sequence dependent. Lastly, drug displacement studies with ISIS 2302 and other concomitant drugs with known protein-binding properties were conducted to provide information on potential drug interactions. Coadministered ISIS 2302 and other high-binding drugs evaluated in this study did not displace one another at supraclinical plasma concentrations and, thus, are not anticipated to cause any pharmacokinetic interaction in the clinic as a result of the displacement of binding to plasma proteins.

Cyclic fatigue resistance, torsional resistance, and metallurgical characteristics of M3 Rotary and M3 Pro Gold NiTi files

PubMed Central

2018-01-01

Objectives To evaluate the mechanical properties and metallurgical characteristics of the M3 Rotary and M3 Pro Gold files (United Dental). Materials and Methods One hundred and sixty new M3 Rotary and M3 Pro Gold files (sizes 20/0.04 and 25/0.04) were used. Torque and angle of rotation at failure (n = 20) were measured according to ISO 3630-1. Cyclic fatigue resistance was tested by measuring the number of cycles to failure in an artificial stainless steel canal (60° angle of curvature and a 5-mm radius). The metallurgical characteristics were investigated by differential scanning calorimetry. Data were analyzed using analysis of variance and the Student-Newman-Keuls test. Results Comparing the same size of the 2 different instruments, cyclic fatigue resistance was significantly higher in the M3 Pro Gold files than in the M3 Rotary files (p < 0.001). No significant difference was observed between the files in the maximum torque load, while a significantly higher angular rotation to fracture was observed for M3 Pro Gold (p < 0.05). In the DSC analysis, the M3 Pro Gold files showed one prominent peak on the heating curve and 2 prominent peaks on the cooling curve. In contrast, the M3 Rotary files showed 1 small peak on the heating curve and 1 small peak on the cooling curve. Conclusions The M3 Pro Gold files showed greater flexibility and angular rotation than the M3 Rotary files, without decrement of their torque resistance. The superior flexibility of M3 Pro Gold files can be attributed to their martensite phase. PMID:29765904

Epidemiology of 3rd generation cephalosporin-resistant Escherichia coli on dairy farms

USDA-ARS?s Scientific Manuscript database

Dairy cattle have been identified as a reservoir for 3rd generation cephalosporin (3GC)-resistant Escherichia coli. We previously identified 3GC-resistant E. coli from manure composite samples of calves and cows in a survey of 80 farms in Pennsylvania. Resistant strains were most frequently isolated...

Radiation resistance of lactobacilli isolated from radurized meat relative to growth and environment. [Lactobacillus sake; Lactobacillus curvatus; Lactobacillus farciminis; Staphylococcus aureus; Salmonella typimurium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hastings, J.W.; Holzapfel, W.H.; Niemand, J.G.

1986-10-01

Of 113 lactobacilli isolated from radurized (5 kGy) minced meat, 7 Lactobacillus sake strains, 1 L. curvatus strain, and 1 L. farciminis strain were used for radiation resistance studies in a semisynthetic substrate (i.e., modified MRS broth). Five reference Lactobacillus spp. one Staphylococcus aureus strain, and one Salmonella typhimurium strain were used for comparative purposes. All L. sake isolates exhibited the phenomenon of being more resistant to gamma-irradiation in the exponential (log) phase than in the stationary phase of their growth cycles by a factor of 28%. Four reference strains also exhibited this phenomenon, with L. sake (DSM 20017) showingmore » a 68% increase in resistance in the log phase over the stationary phase. This phenomenon was not common to all bacteria tested and is not common to all strains with high radiation resistance. Four L. sake isolates and three reference strains were used in radiation sensitivity testing in a natural food system (i.e., meat). The bacteria were irradiated in minced meat and packaged under four different conditions (air, vacuum, CO/sub 2/, and N/sub 2/). Organisms exhibited the highest death rate (lowest D/sub 10/ values (doses required to reduce the logarithm of the bacterial population by 1) under CO/sub 2/ packaging conditions, but resistance to irradiation was increased under N/sub 2/. The D/sup 10/ values of the isolates were generally greater than those of the reference strains. The D/sup 10/ values were also higher (approximately two times) in meat than in a semisynthetic growth medium.« less

Meta-analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

PubMed Central

Fan, Wen-Ying; Liu, Ning-Pu

2015-01-01

AIM To collectively evaluate the association of intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism (rs5498) with diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM). METHODS Overall review of available literatures relating K469E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios (ORs). Potential sources of heterogeneity and bias were explored. RESULTS Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469E polymorphism with DR (P>0.05). A statistically significant association was detected between the K469E polymorphism and proliferative diabetic retinopathy (PDR) in Asians only in dominant model (GG+AG vs AA) with pooled OR of 0.729 (95%CI: 0.564-0.942, P=0.016, Pheterogeneity=0.143), however, this association was not detected in recessive model (GA+AA vs GG; OR=1.178, 95%CI: 0.898-1.545, P=0.236, Pheterogeneity=0.248) or allelic model (G vs A; OR=0.769, 95% CI: 0.576-1.026, P=0.074, Pheterogeneity=0.094). No publication bias was found by Funnel plot, Begg's and Egger's test. CONCLUSION This research found no statistically significant association between ICAM-1 gene K469E polymorphism and DR in patients with T2DM, but showed significant association of the K469E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion. PMID:26086016

Different effects of antisense RelA p65 and NF-kappaB1 p50 oligonucleotides on the nuclear factor-kappaB mediated expression of ICAM-1 in human coronary endothelial and smooth muscle cells.

PubMed

Voisard, R; Huber, N; Baur, R; Susa, M; Ickrath, O; Both, A; Koenig, W; Hombach, V

2001-01-01

Activation of nuclear factor-kappaB (NF-kappaB) is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-alpha (TNF-alpha) induced and NF-kappaB mediated expression of intercellular adhesion molecule-1 (ICAM-1) can be inhibited by antisense RelA p65 and NF-kappaB1 p50 oligonucleotides (RelA p65 and NF-kappaB1 p50). Smooth muscle cells (SMC) from human coronary plaque material (HCPSMC, plaque material of 52 patients), SMC from the human coronary media (HCMSMC), human endothelial cells (EC) from umbilical veins (HUVEC), and human coronary EC (HCAEC) were successfully isolated (HCPSMC, HUVEC), identified and cultured (HCPSMC, HCMSMC, HUVEC, HCAEC). 12 hrs prior to TNF-alpha stimulus (20 ng/mL, 6 hrs) RelA p65 and NF-kappaB1 p50 (1, 2, 4, 10, 20, and 30 microM) and controls were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent inhibition of ICAM-1 expression after adding of both RelA p65 and NF-kappaB1 p50. No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF-kappaB1 p50. A moderate inhibition of ICAM-1 expression was found after simultaneous addition of RelA p65 and NF-kappaB1 p50 to HCPSMC, no inhibitory effect was detected after individual addition of RelA p65 and NF-kappaB1 p50. The data point out that differences exist in the NF-kappaB mediated expression of ICAM-1 between EC and SMC. Experimental antisense strategies directed against RelA p65 and NF-kappaB1 p50 in early atherosclerosis and restenosis are promising in HCAEC but will be confronted with redundant pathways in HCMSMC and HCPSMC.

Combining 2D angiogenesis and 3D osteosarcoma microtissues to improve vascularization.

PubMed

Chaddad, Hassan; Kuchler-Bopp, Sabine; Fuhrmann, Guy; Gegout, Hervé; Ubeaud-Sequier, Geneviève; Schwinté, Pascale; Bornert, Fabien; Benkirane-Jessel, Nadia; Idoux-Gillet, Ysia

2017-11-15

Angiogenesis is now well known for being involved in tumor progression, aggressiveness, emergence of metastases, and also resistance to cancer therapies. In this study, to better mimic tumor angiogenesis encountered in vivo, we used 3D culture of osteosarcoma cells (MG-63) that we deposited on 2D endothelial cells (HUVEC) grown in monolayer. We report that endothelial cells combined with tumor cells were able to form a well-organized network, and that tubule-like structures corresponding to new vessels infiltrate tumor spheroids. These vessels presented a lumen and expressed specific markers as CD31 and collagen IV. The combination of 2D endothelial cells and 3D microtissues of tumor cells also increased expression of angiogenic factors as VEGF, CXCR4 and ICAM1. The cell environment is the key point to develop tumor vascularization in vitro and to be closer to tumor encountered in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Systematic functional characterization of resistance to PI3K inhibition in breast cancer

PubMed Central

Treacy, Daniel J.; Luo, Flora; Ghandi, Mahmoud; Castel, Pau; Scaltriti, Maurizio; Baselga, Jose; Garraway, Levi A.

2016-01-01

PIK3CA (which encodes the phosphoinositide-3 kinase (PI3K) alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, PIM kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacological inhibition of PIM and PI3K overcame this resistance mechanism. We also observed upregulated PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression is mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers. PMID:27604488

Compact synchrotron radiation depth lithography facility

NASA Astrophysics Data System (ADS)

Knüppel, O.; Kadereit, D.; Neff, B.; Hormes, J.

1992-01-01

X-ray depth lithography allows the fabrication of plastic microstructures with heights of up to 1 mm but with the smallest possible lateral dimensions of about 1 μm. A resist is irradiated with ``white'' synchrotron radiation through a mask that is partially covered with x-ray absorbing microstructures. The plastic microstructure is then obtained by a subsequent chemical development of the irradiated resist. In order to irradiate a reasonably large resist area, the mask and the resist have to be ``scanned'' across the vertically thin beam of the synchrotron radiation. A flexible, nonexpensive and compact scanner apparatus has been built for x-ray depth lithography at the beamline BN1 at ELSA (the 3.5 GeV Electron Stretcher and Accelerator at the Physikalisches Institut of Bonn University). Measurements with an electronic water level showed that the apparatus limits the scanner-induced structure precision to not more than 0.02 μm. The whole apparatus is installed in a vacuum chamber thus allowing lithography under different process gases and pressures.

Radiation Enhances Regulatory T Cell Representation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei

2011-11-15

Purpose: Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. Methods and Materials: Treg cells were identified as a CD4{sup +}CD25{sup hi}Foxp3{sup +} lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4{sup +}CD25{sup hi}Foxp3{sup +}more » Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. Conclusions: We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.« less

Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells.

PubMed

Bhatt, Anant Narayan; Chauhan, Ankit; Khanna, Suchit; Rai, Yogesh; Singh, Saurabh; Soni, Ravi; Kalra, Namita; Dwarakanath, Bilikere S

2015-05-01

Cancer cells exhibit increased glycolysis for ATP production (the Warburg effect) and macromolecular biosynthesis; it is also linked with therapeutic resistance that is generally associated with compromised respiratory metabolism. Molecular mechanisms underlying radio-resistance linked to elevated glycolysis remain incompletely understood. We stimulated glycolysis using mitochondrial respiratory modifiers (MRMs viz. di-nitro phenol, DNP; Photosan-3, PS3; Methylene blue, MB) in established human cell lines (HEK293, BMG-1 and OCT-1). Glucose utilization and lactate production, levels of glucose transporters and glycolytic enzymes were investigated as indices of glycolysis. Clonogenic survival, DNA repair and cytogenetic damage were studied as parameters of radiation response. MRMs induced the glycolysis by enhancing the levels of two important regulators of glucose metabolism GLUT-1 and HK-II and resulted in 2 fold increase in glucose consumption and lactate production. This increase in glycolysis resulted in resistance against radiation-induced cell death (clonogenic survival) in different cell lines at an absorbed dose of 5 Gy. Inhibition of glucose uptake and glycolysis (using fasentin, 2-deoxy-D-glucose and 3-bromopyruvate) in DNP treated cells failed to increase the clonogenic survival of irradiated cells, suggesting that radio-resistance linked to inhibition of mitochondrial respiration is glycolysis dependent. Elevated glycolysis also facilitated rejoining of radiation-induced DNA strand breaks by activating both non-homologous end joining (NHEJ) and homologous recombination (HR) pathways of DNA double strand break repair leading to a reduction in radiation-induced cytogenetic damage (micronuclei formation) in these cells. These findings suggest that enhanced glycolysis generally observed in cancer cells may be responsible for the radio-resistance, partly by enhancing the repair of DNA damage.

Resistivity imaging of Aluto-Langano geothermal field using 3-D magnetotelluric inversion

NASA Astrophysics Data System (ADS)

Cherkose, Biruk Abera; Mizunaga, Hideki

2018-03-01

Magnetotelluric (MT) method is a widely used geophysical method in geothermal exploration. It is used to image subsurface resistivity structures from shallow depths up to several kilometers of depth. Resistivity imaging using MT method in high-enthalpy geothermal systems is an effective tool to identify conductive clay layers that cover the geothermal systems and to detect a potential reservoir. A resistivity model is vital for deciding the location of pilot and production sites at the early stages of a geothermal project. In this study, a 3-D resistivity model of Aluto-Langano geothermal field was constructed to map structures related to a geothermal resource. The inversion program, ModEM was used to recover the 3-D resistivity model of the study area. The 3-D inversion result revealed the three main resistivity structures: a high-resistivity surface layer related to unaltered volcanic rocks at shallow depth, underlain by a conductive zone associated with the presence of conductive clay minerals, predominantly smectite. Beneath the conductive layer, the resistivity increases gradually to higher values related to the formation of high-temperature alteration minerals such as chlorite and epidote. The resistivity model recovered from 3-D inversion in Aluto-Langano corresponds very well to the conceptual model for high-enthalpy volcanic geothermal systems. The conductive clay cap is overlying the resistive propylitic upflow zone as confirmed by the geothermal wells in the area.

Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer.

PubMed

Le, Xiuning; Antony, Rajee; Razavi, Pedram; Treacy, Daniel J; Luo, Flora; Ghandi, Mahmoud; Castel, Pau; Scaltriti, Maurizio; Baselga, Jose; Garraway, Levi A

2016-10-01

PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacologic inhibition of PIM and PI3K overcame this resistance mechanism. We also observed increased PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression was mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers. PIM kinase overexpression confers resistance to small-molecule PI3K inhibitors. Combined inhibition of PIM and PI3K may therefore be warranted in a subset of breast cancers. Cancer Discov; 6(10); 1134-47. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1069. ©2016 American Association for Cancer Research.

Outside-in HLA class I signaling regulates ICAM-1 clustering and endothelial cell-monocyte interactions via mTOR in transplant antibody-mediated rejection.

PubMed

Salehi, Sahar; Sosa, Rebecca A; Jin, Yi-Ping; Kageyama, Shoichi; Fishbein, Michael C; Rozengurt, Enrique; Kupiec-Weglinski, Jerzy W; Reed, Elaine F

2018-05-01

Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy (TAV) is the major obstacle for long-term survival of solid organ transplants. AMR is caused by donor-specific antibodies to HLA, which contribute to TAV by initiating outside-in signaling transduction pathways that elicit monocyte recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR) inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell activation and monocyte recruitment. We used an in vitro model to assess monocyte binding to HLA I Ab-activated endothelial cells and found mTOR inhibition reduced ezrin/radixin/moesin (ERM) phosphorylation, intercellular adhesion molecule 1 (ICAM-1) clustering, and monocyte firm adhesion to HLA I Ab-activated endothelium. Further, in a mouse model of AMR, in which C57BL/6. RAG1 -/- recipients of BALB/c cardiac allografts were passively transferred with donor-specific MHC I antibodies, mTOR inhibition significantly reduced vascular injury, ERM phosphorylation, and macrophage infiltration of the allograft. Taken together, these studies indicate mTOR inhibition suppresses ERM phosphorylation in endothelial cells, which impedes ICAM-1 clustering in response to HLA class I Ab and prevents macrophage infiltration into cardiac allografts. These findings indicate a novel therapeutic application for mTOR inhibitors to disrupt endothelial cell-monocyte interactions during AMR. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Direct observation of oxygen vacancy-driven structural and resistive phase transitions in La2/3Sr1/3MnO3

NASA Astrophysics Data System (ADS)

Yao, Lide; Inkinen, Sampo; van Dijken, Sebastiaan

2017-02-01

Resistive switching in transition metal oxides involves intricate physical and chemical behaviours with potential for non-volatile memory and memristive devices. Although oxygen vacancy migration is known to play a crucial role in resistive switching of oxides, an in-depth understanding of oxygen vacancy-driven effects requires direct imaging of atomic-scale dynamic processes and their real-time impact on resistance changes. Here we use in situ transmission electron microscopy to demonstrate reversible switching between three resistance states in epitaxial La2/3Sr1/3MnO3 films. Simultaneous high-resolution imaging and resistance probing indicate that the switching events are caused by the formation of uniform structural phases. Reversible horizontal migration of oxygen vacancies within the manganite film, driven by combined effects of Joule heating and bias voltage, predominantly triggers the structural and resistive transitions. Our findings open prospects for ionotronic devices based on dynamic control of physical properties in complex oxide nanostructures.

Inhibitors of adhesion molecules expression; the synthesis and pharmacological properties of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives.

PubMed

Kaneko, Toshihiko; Clark, Richard S J; Ohi, Norihito; Kawahara, Tetsuya; Akamatsu, Hiroshi; Ozaki, Fumihiro; Kamada, Atsushi; Okano, Kazuo; Yokohama, Hiromitsu; Muramoto, Kenzo; Ohkuro, Masayoshi; Takenaka, Osamu; Kobayashi, Seiichi

2002-07-01

During a search for novel, orally-active inhibitors of upregulation of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), we found a new series of 10H-pyrazino[2,3-b][1,4]benzothiazine derivatives to be potent ICAM-1 inhibitors. Of these compounds, N-[1-(10H-Pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)piperidin-4-yl]-N',N'-dimethylsulfamide 7p showed the potent oral inhibitory activities against neutrophil migration in a murine interleukin-1 (IL-1) induced paw inflammation model. The synthesis and structure-activity relationships of these amide derivatives are described.

Swift heavy ion-induced radiation damage in isotropic graphite studied by micro-indentation and in-situ electrical resistivity

NASA Astrophysics Data System (ADS)

Hubert, Christian; Voss, Kay Obbe; Bender, Markus; Kupka, Katharina; Romanenko, Anton; Severin, Daniel; Trautmann, Christina; Tomut, Marilena

2015-12-01

Due to its excellent thermo-physical properties and radiation hardness, isotropic graphite is presently the most promising material candidate for new high-power ion accelerators which will provide highest beam intensities and energies. Under these extreme conditions, specific accelerator components including production targets and beam protection modules are facing the risk of degradation due to radiation damage. Ion-beam induced damage effects were tested by irradiating polycrystalline, isotropic graphite samples at the UNILAC (GSI, Darmstadt) with 4.8 MeV per nucleon 132Xe, 150Sm, 197Au, and 238U ions applying fluences between 1 × 1011 and 1 × 1014 ions/cm2. The overall damage accumulation and its dependence on energy loss of the ions were studied by in situ 4-point resistivity measurements. With increasing fluence, the electric resistivity increases due to disordering of the graphitic structure. Irradiated samples were also analyzed off-line by means of micro-indentation in order to characterize mesoscale effects such as beam-induced hardening and stress fields within the specimen. With increasing fluence and energy loss, hardening becomes more pronounced.

Investigation of resistive switching behaviours in WO3-based RRAM devices

NASA Astrophysics Data System (ADS)

Li, Ying-Tao; Long, Shi-Bing; Lü, Hang-Bing; Liu, Qi; Wang, Qin; Wang, Yan; Zhang, Sen; Lian, Wen-Tai; Liu, Su; Liu, Ming

2011-01-01

In this paper, a WO3-based resistive random access memory device composed of a thin film of WO3 sandwiched between a copper top and a platinum bottom electrodes is fabricated by electron beam evaporation at room temperature. The reproducible resistive switching, low power consumption, multilevel storage possibility, and good data retention characteristics demonstrate that the Cu/WO3/Pt memory device is very promising for future nonvolatile memory applications. The formation and rupture of localised conductive filaments is suggested to be responsible for the observed resistive switching behaviours.

Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome.

PubMed

Singh, Vijay K; Pollard, Harvey B

2015-01-01

Acute radiation exposure induces apoptosis of tissues in the hematopoietic, digestive, cutaneous, cardiovascular and nervous systems; extensive apoptosis of these tissues ultimately leads to acute radiation syndrome. A novel strategy for developing radiation countermeasures has been to imitate the genetic mechanisms acquired by radiation-resistant tumors. Two mechanisms that underlie this ability of tumor cells are the p53 and NF-κB pathways. The loss of p53 function results in the inactivation of pro-apoptotic control mechanisms, while constitutive activation of NF-κB results in the up-regulation of anti-apoptotic genes. Various Toll-like receptor ligands are capable of up regulating the NF-κB pathway, which increases radio-resistance and reduces radiation-induced apoptosis in various tissues. Several Toll-like receptor ligands have been patented and are currently under development as radiation countermeasures for acute radiation syndrome. Ongoing studies suggest that a few of these attractive agents are progressing well along the US FDA approval pathway to become radiation countermeasures.

Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome

PubMed Central

Singh, Vijay K; Pollard, Harvey B

2015-01-01

Acute radiation exposure induces apoptosis of tissues in the hematopoietic, digestive, cutaneous, cardiovascular and nervous systems; extensive apoptosis of these tissues ultimately leads to acute radiation syndrome. A novel strategy for developing radiation countermeasures has been to imitate the genetic mechanisms acquired by radiation-resistant tumors. Two mechanisms that underlie this ability of tumor cells are the p53 and NF-κB pathways. The loss of p53 function results in the inactivation of pro-apoptotic control mechanisms, while constitutive activation of NF-κB results in the up-regulation of anti-apoptotic genes. Various Toll-like receptor ligands are capable of up regulating the NF-κB pathway, which increases radio-resistance and reduces radiation-induced apoptosis in various tissues. Several Toll-like receptor ligands have been patented and are currently under development as radiation countermeasures for acute radiation syndrome. Ongoing studies suggest that a few of these attractive agents are progressing well along the US FDA approval pathway to become radiation countermeasures. PMID:26135043

Thermomechanical treatment for improved neutron irradiation resistance of austenitic alloy (Fe-21Cr-32Ni)

DOE Office of Scientific and Technical Information (OSTI.GOV)

L. Tan; J. T. Busby; H. J. M. Chichester

2013-06-01

An optimized thermomechanical treatment (TMT) applied to austenitic alloy 800H (Fe-21Cr-32Ni) had shown significant improvements in corrosion resistance and basic mechanical properties. This study examined its effect on radiation resistance by irradiating both the solution-annealed (SA) and TMT samples at 500 degrees C for 3 dpa. Microstructural characterization using transmission electron microscopy revealed that the radiation-induced Frank loops, voids, and y'-Ni3(Ti,Al) precipitates had similar sizes between the SA and TMT samples. The amounts of radiation-induced defects and more significantly y' precipitates, however, were reduced in the TMT samples. These reductions would approximately reduce by 40.9% the radiation hardening compared tomore » the SA samples. This study indicates that optimized-TMT is an economical approach for effective overall property improvements.« less

Luminescence and radiation resistance of undoped NaI crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiran, N., E-mail: shiran@isc.kharkov.com; Boiaryntseva, I.; Gektin, A.

2014-11-15

Highlights: • The performance of NaI scintillators depends on luminescence properties. • A criterion of crystals’ purity level is radiation colorability at room temperature. • The traces of the most dangerous impurities were detected. • Crucial role in efficiency of pure NaI scintillator play the crystal perfection. - Abstract: Undoped NaI single crystal is an excellent scintillator at low temperature. However, scintillation parameters of different quality crystals vary in a wide range, significantly exceeding measurement error. Experimental data demonstrate the features of luminescence, radiation induced coloration, and afterglow dependence on the quality of nominally pure crystals. It is found thatmore » defects level that allows to elucidate artefacts introduced by traces of harmful impurities corresponds to 3 × 10{sup 15} cm{sup −3} that significantly overhead accuracy of chemical and absorption analysis. It is shown that special raw material treatment before and during the single crystal growth allows to reach NaI purity level that avoids impurities influence to the basic luminescence data.« less

Andrographis paniculata Diterpenoids Protect against Radiation-Induced Transformation in BALB/3T3 Cells.

PubMed

Nantajit, Danupon; Jetawattana, Suwimol; Suriyo, Tawit; Grdina, David J; Satayavivad, Jutamaad

2017-07-01

One of the most concerning side effects of exposure to radiation are the carcinogenic risks. To reduce the negative effects of radiation, both cytoprotective and radioprotective agents have been developed. However, little is known regarding their potential for suppressing carcinogenesis. Andrographis paniculata , a plant, with multiple medicinal uses that is commonly used in traditional medicine, has three major constituents known to have cellular antioxidant activity: andrographolide (AP1); 14-deoxy-11,12-didehydroandrographolide (AP3); and neoandrographolide (AP4). In our study, we tested these elements for their radioprotective properties as well as their anti-neoplastic effects on transformation using the BALB/3T3 cell model. All three compounds were able to reduce radiation-induced DNA damage. However, AP4 appeared to have superior radioprotective properties compared to the other two compounds, presumably by protecting mitochondrial function. The compound was able to suppress radiation-induced cellular transformation through inhibition of STAT3. Treatment with AP4 also reduced expressions of MMP-2 and MMP-9. These results suggest that AP4 could be further studied and developed into an anti-transformation/carcinogenic drug as well as a radioprotective agent.

Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer.

PubMed

Chen, Yongshun; Li, Xiaohong; Guo, Leiming; Wu, Xiaoyuan; He, Chunyu; Zhang, Song; Xiao, Yanjing; Yang, Yuanyuan; Hao, Daxuan

2015-08-01

Radiotherapy is an effective treatment for esophageal cancer; however, tumor resistance to radiation remains a major biological problem. The present study aimed to investigate whether inhibition of autophagy may decrease overall tumor resistance to radiation. The effects of the autophagy inhibitor 3-methyladenine (3-MA) on radiosensitivity were tested in the EC9706 human esophageal squamous cell carcinoma cell line by colony formation assay. Furthermore, the synergistic cytotoxic effects of 3-MA and radiation were assessed in a tumor xenograft model in nude mice. Mechanistic studies were performed using flow cytometry, immunohistochemistry and western blot analysis. The results of the present study demonstrated that radiation induced an accumulation of autophagosomes and 3-MA effectively inhibited radiation-induced autophagy. Inhibition of autophagy was shown to significantly increase the radiosensitivity of the tumors in vitro and in vivo. The enhancement ratio of sensitization in EC9706 cells was 1.76 when the cells were treated with 10 mM 3-MA, alongside ionizing radiation. In addition, autophagy inhibition increased apoptosis and reduced tumor cell proliferation. The combination of radiation and autophagy inhibition resulted in a significant reduction in tumor volume and vasculature in the murine model. The present study demonstrated in vitro and in vivo that radiation-induced autophagy has a protective effect against cell death, and inhibition of autophagy is able to enhance the radiosensitivity of esophageal squamous cell carcinoma.

Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer

PubMed Central

CHEN, YONGSHUN; LI, XIAOHONG; GUO, LEIMING; WU, XIAOYUAN; HE, CHUNYU; ZHANG, SONG; XIAO, YANJING; YANG, YUANYUAN; HAO, DAXUAN

2015-01-01

Radiotherapy is an effective treatment for esophageal cancer; however, tumor resistance to radiation remains a major biological problem. The present study aimed to investigate whether inhibition of autophagy may decrease overall tumor resistance to radiation. The effects of the autophagy inhibitor 3-methyladenine (3-MA) on radiosensitivity were tested in the EC9706 human esophageal squamous cell carcinoma cell line by colony formation assay. Furthermore, the synergistic cytotoxic effects of 3-MA and radiation were assessed in a tumor xenograft model in nude mice. Mechanistic studies were performed using flow cytometry, immunohistochemistry and western blot analysis. The results of the present study demonstrated that radiation induced an accumulation of autophagosomes and 3-MA effectively inhibited radiation-induced autophagy. Inhibition of autophagy was shown to significantly increase the radiosensitivity of the tumors in vitro and in vivo. The enhancement ratio of sensitization in EC9706 cells was 1.76 when the cells were treated with 10 mM 3-MA, alongside ionizing radiation. In addition, autophagy inhibition increased apoptosis and reduced tumor cell proliferation. The combination of radiation and autophagy inhibition resulted in a significant reduction in tumor volume and vasculature in the murine model. The present study demonstrated in vitro and in vivo that radiation-induced autophagy has a protective effect against cell death, and inhibition of autophagy is able to enhance the radiosensitivity of esophageal squamous cell carcinoma. PMID:25891159

38 CFR 3.715 - Radiation Exposure Compensation Act of 1990, as amended.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Radiation Exposure... Benefits and Elections § 3.715 Radiation Exposure Compensation Act of 1990, as amended. (a) Compensation. (1) A radiation-exposed veteran, as defined in 38 CFR 3.309(d)(3), who receives a payment under the...

38 CFR 3.715 - Radiation Exposure Compensation Act of 1990, as amended.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Radiation Exposure... Benefits and Elections § 3.715 Radiation Exposure Compensation Act of 1990, as amended. (a) Compensation. (1) A radiation-exposed veteran, as defined in 38 CFR 3.309(d)(3), who receives a payment under the...

38 CFR 3.715 - Radiation Exposure Compensation Act of 1990, as amended.