Effects of Mg2+ and adenine nucleotides on thymidylate synthetase from different mouse tumors.
Rode, W; Jastreboff, M M
1984-01-01
Magnesium ions variably influenced activity of highly purified thymidylate synthetase preparations from different mouse tumors, activating the enzyme from Ehrlich ascites carcinoma (EAC) cells and inhibiting the enzyme from L1210 and L5178Y cells and from 5-fluorodeoxyuridine (FdUrd)-resistant EAC cells. In the presence of Mg2+ in a concentration resulting in either maximum activation or inhibition (25-30 mM) the enzymes from both the sensitive and FdUrd-resistant EAC lines and L5178Y cells were activated by ATP. Under the same conditions of Mg2+ concentration ADP and AMP inhibited the enzyme from the parental but not from the FdUrd-resistant EAC cells.
Kong, Jianping; Whelan, Kelly A.; Laczkó, Dorottya; Dang, Brendan; Monroig, Angeliz Caro; Soroush, Ali; Falcone, John; Amaravadi, Ravi K.; Rustgi, Anil K.; Ginsberg, Gregory G; Falk, Gary W; Nakagawa, Hiroshi; Lynch, John P.
2015-01-01
Autophagy is a highly conserved mechanism that is activated during cellular stress. We hypothesized that autophagy may be induced by acid reflux, which causes injury and inflammation, and therefore contributes to the pathogenesis of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). Currently, the role of autophagy in BE and EAC is poorly studied. We quantitatively define autophagy levels in human BE cell lines, a transgenic mouse model of BE, and human BE and EAC biopsies. Human non-dysplastic BE had the highest basal number of autophagic vesicles (AVs), while AVs were reduced in normal squamous cells and dysplastic BE cells, and nearly absent in EAC. To demonstrate a functional role for autophagy in BE pathogenesis, normal squamous (STR), non-dysplastic BE (CPA), dysplastic BE (CPD), and esophageal adenocarcinoma (OE19) cell lines were exposed to an acid pulse (pH3.5) followed by incubation in the presence or absence of chloroquine, an autophagy inhibitor. Acid exposure increased reactive oxygen species (ROS) levels in STR and CPA cells. Chloroquine alone had a small impact on intracellular ROS or cell survival. However, combination of chloroquine with the acid pulse resulted in a significant increase in ROS levels at 6 hours in STR and CPA cells, and increased cell death in all cell lines. These findings establish increased numbers of AVs in human BE compared to normal squamous or EAC, and suggest that autophagy functions to improve cell survival after acid reflux injury. Autophagy may thus play a critical role in BE pathogenesis and progression. PMID:26373456
Kauttu, T; Mustonen, H; Vainionpää, S; Krogerus, L; Ilonen, I; Räsänen, J; Salo, J; Puolakkainen, P
2017-01-01
Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.
Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines.
Hanu, Christine; Wong, Raimond; Sur, Ranjan K; Hayward, Joseph E; Seymour, Colin; Mothersill, Carmel
2017-02-01
To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure. Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells. We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy. These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals.
IGFBP2 modulates the chemoresistant phenotype in esophageal adenocarcinoma
Myers, Amy L.; Lin, Lin; Nancarrow, Derek J.; Wang, Zhuwen; Ferrer-Torres, Daysha; Thomas, Dafydd G.; Orringer, Mark B.; Lin, Jules; Reddy, Rishindra M.; Beer, David G.; Chang, Andrew C.
2015-01-01
Esophageal adenocarcinoma (EAC) patients commonly present with advanced stage disease and demonstrate resistance to therapy, with response rates below 40%. Understanding the molecular mechanisms of resistance is crucial for improvement of clinical outcomes. IGFBP2 is a member of the IGFBP family of proteins that has been reported to modulate both IGF and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types. In this study, high IGFBP2 expression was observed in a subset of primary EACs and was found to be significantly higher in patients with shorter disease-free intervals as well as in treatment-resistant EACs as compared to chemonaive EACs. Modulation of IGFBP2 expression in EAC cell lines promoted cell proliferation, migration and invasion, implicating a role in the metastatic potential of these cells. Additionally, knockdown of IGFBP2 sensitized EAC cells to cisplatin in a serum-dependent manner. Further in vitro exploration into this chemosensitization implicated both the AKT and ERK pathways. Silencing of IGFBP2 enhanced IGF1-induced immediate activation of AKT and reduced cisplatin-induced ERK activation. Addition of MEK1/2 (selumetinib or trametinib) or AKT (AKT Inhibitor VIII) inhibitors enhanced siIGFBP2-induced sensitization of EAC cells to cisplatin. These results suggest that targeted inhibition of IGFBP2 alone or together with either the MAPK or PI3K/AKT signaling pathway in IGFBP2-overexpressing EAC tumors may be an effective approach for sensitizing resistant EACs to standard neoadjuvant chemotherapy. PMID:26317790
Smina, T P; Mathew, J; Janardhanan, K K
2016-04-30
G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities.
Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine
Ahrens, Theresa D; Timme, Sylvia; Hoeppner, Jens; Ostendorp, Jenny; Hembach, Sina; Follo, Marie; Hopt, Ulrich T; Werner, Martin; Busch, Hauke; Boerries, Melanie; Lassmann, Silke
2015-01-01
Esophageal cancers are highly aggressive tumors with poor prognosis despite some recent advances in surgical and radiochemotherapy treatment options. This study addressed the feasibility of drugs targeting epigenetic modifiers in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells. We tested inhibition of histone deacetylases (HDACs) by SAHA, MS-275, and FK228, inhibition of DNA methyltransferases by Azacytidine (AZA) and Decitabine (DAC), and the effect of combination treatment using both types of drugs. The drug targets, HDAC1/2/3 and DNMT1, were expressed in normal esophageal epithelium and tumor cells of ESCC or EAC tissue specimens, as well as in non-neoplastic esophageal epithelial (Het-1A), ESCC (OE21, Kyse-270, Kyse-410), and EAC (OE33, SK-GT-4) cell lines. In vitro, HDAC activity, histone acetylation, and p21 expression were similarly affected in non-neoplastic, ESCC, and EAC cell lines post inhibitor treatment. Combined MS-275/AZA treatment, however, selectively targeted esophageal cancer cell lines by inducing DNA damage, cell viability loss, and apoptosis, and by decreasing cell migration. Non-neoplastic Het-1A cells were protected against HDACi (MS-275)/AZA treatment. RNA transcriptome analyses post MS-275 and/or AZA treatment identified novel regulated candidate genes (up: BCL6, Hes2; down: FAIM, MLKL), which were specifically associated with the treatment responses of esophageal cancer cells. In summary, combined HDACi/AZA treatment is efficient and selective for the targeting of esophageal cancer cells, despite similar target expression of normal and esophageal cancer epithelium, in vitro and in human esophageal carcinomas. The precise mechanisms of action of treatment responses involve novel candidate genes regulated by HDACi/AZA in esophageal cancer cells. Together, targeting of epigenetic modifiers in esophageal cancers may represent a potential future therapeutic approach. PMID:25923331
Epidermal growth factor expression in esophageal adenocarcinoma: a clinically relevant target?
Harper, Nicholas; Li, Yan; Farmer, Russell; Martin, Robert C G
2012-05-01
There has been recent widespread enthusiasm in epidermal growth factor (EGFR) as a molecularly active target in esophageal adenocarcinoma (EAC). However, there is limited data on the extent of EGFR expression in EAC. Thus, the aim of this study was to evaluated EGFR, pErk1/2, and total Erk1/2 expression in malignant and benign specimens. Baseline expression of EGFR in the human normal squamous, Barrett's, and EAC cell lines were determined as well as after bile acid treatment and curcumin pretreatment. In addition, EGFR expression was also evaluated in 60 matched normal and malignant EAC resected specimens. The in vitro studies in the Het-1a, BarT, and OE19 cell lines failed to show any measurable expression of EGFR via Western blot technique. The marker serving as the positive control for the study, MnSOD, showed expression in each cell line for all three treatment regimens at approximately 24 kDa EGFR, showing moderate staining in the malignant tumor specimens and low staining in the benign tissue specimens. pErk1/2 showed low staining in the malignant tumor specimens and no staining in the benign tissue specimens. Total Erk1/2 showed high staining in both the malignant tumor specimens and benign tissue specimens. The differences in the mean staining scores for the malignant versus benign tissue specimens for pErk1/2 and total Erk1/2 are not statistically significant (p = 0.0726 and p = 0.7054, respectively). Thus, in conclusion, EGFR expression has been confirmed to be limited to non-existent in EAC and thus its use as a clinically active target is limited at best. Prior to the use of these expensive anti-EGFR therapies, confirmation of overexpression should be verified.
Jastreboff, M M; Zielińska, Z M
1983-01-01
A subline of Ehrlich ascites carcinoma (EAC) cells resistant to 5-fluoro-2'-deoxy-uridine (FdUrd) was developed by continuous exposure to progressively increasing concentrations of the drug (35-75 mg/kg per day) during 15 passages through mice. Since then, the EAC cells have been retransplanted more than 80 times through drug-untreated mice and continue to be resistant. After adaptation to growth in suspension culture the drug-adapted cells were 1000 times more resistant to FdUrd in comparison with parental ones, and remained near-tetraploid with doubling time longer than in parental line. The activity of thymidine kinase was deeply depressed (100-fold) whereas that of thymidylate synthetase several-fold increased in the resistant EAC cells, both grown in vivo and in vitro.
Mari, Luigi; Hoefnagel, Sanne J M; Zito, Domenico; van de Meent, Marian; van Endert, Peter; Calpe, Silvia; Sancho Serra, Maria Del Carmen; Heemskerk, Mirjam H M; van Laarhoven, Hanneke W M; Hulshof, Maarten C C M; Gisbertz, Susanne S; Medema, Jan Paul; van Berge Henegouwen, Mark I; Meijer, Sybren L; Bergman, Jacques J G H M; Milano, Francesca; Krishnadath, Kausilia K
2018-06-07
Immune checkpoint inhibition may affect growth or progression of highly aggressive cancers, such as esophageal adenocarcinoma (EAC). We investigated the regulation of expression of major histocompatibility complex, class 1 (MHC-I) proteins (encoded by HLA-A, HLA-B, and HLA-C) and the immune response to EACs in patient samples. We performed quantitative PCR array analyses of OE33 cells and OE19 cells, which express different levels of the ATP binding cassette subfamily B member 1 (TAP1) and TAP2, required for antigen presentation by MHC-I, to identify microRNAs that regulate their expression. We performed luciferase assays to validate interactions between microRNAs and potential targets. We overexpressed candidate microRNAs in OE33, FLO-1, and OACP4 C cell lines and performed quantitative PCR, immunoblot, and flow cytometry analyses to identify changes in mRNA and protein expression; we studied the effects of cytotoxic T cells. We performed microRNA in situ hybridization, RNA-sequencing, and immunohistochemical analyses of tumor tissues from 51 untreated patients with EAC in the Netherlands. Clinical and survival data were collected for patients, and EACs subtypes were determined. We found OE19 cells to have increased levels of 7 microRNAs. Of these, we found binding sites for microRNA 125a (MIR125a)-5p in the 3'UTR of the TAP2 mRNA and binding sites for MIR148a-3p in 3'UTRs of HLA-A, HLA-B, and HLA-C mRNAs. Overexpression of these microRNAs reduced expression of TAP2 in OE33, FLO-1, and OACP4 C cells, and reduced cell-surface levels of MHC-I. OE33 cells that expressed the viral peptide BZLF1 were killed by cytotoxic T cells, whereas OE33 that overexpressed MIR125a-5p or MIR 148a along with BZLF1 were not. In EAC and non-tumor tissues, levels of MIR125a-5p correlated inversely with levels of TAP2 protein. High expression of TAP1 by EAC correlated with significantly shorter overall survival times of patients. EACs that expressed high levels of TAP1 and genes involved in antigen presentation also expressed high levels of genes that regulate the adaptive immune response, PD-L1, PD-L2, and IDO1; these EACs had a poor response to neo-adjuvant chemoradiotherapy and associated with shorter overall survival times of patients. In studies of EAC cell lines and tumor tissues, we found increased levels of MIR125a-5p and MIR148a-3p to reduce levels of TAP2 and MHC-I, required for antigen presentation. High expression of MHC-I molecules by EAC correlated with markers of an adaptive immune response and significantly shorter overall survival times of patients. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Bandla, Santhoshi; Peters, Jeffrey H; Ruff, David; Chen, Shiaw-Min; Li, Chieh-Yuan; Song, Kunchang; Thoms, Kimberly; Litle, Virginia R; Watson, Thomas; Chapurin, Nikita; Lada, Michal; Pennathur, Arjun; Luketich, James D; Peterson, Derick; Dulak, Austin; Lin, Lin; Bass, Adam; Beer, David G; Godfrey, Tony E; Zhou, Zhongren
2014-07-01
To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells. Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma (EAC), but the appropriate histologic definition of Barrett's esophagus is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells whereas nongoblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. Although IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk, then they would harbor similar genetic aberrations in genes associated with EAC. Ninety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities were identified using microarrays and fluorescence in situ hybridization. Targeted sequencing of all exons from 20 EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq DNA sequencing. Frequent copy number abnormalities targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In 1 subject, fluorescence in situ hybridization confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 nonsynonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples. This study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.
Kestens, Christine; Siersema, Peter D.; Offerhaus, G. Johan A.; van Baal, Jantine W. P. M.
2016-01-01
Background Bone morphogenetic protein 4 (BMP4) signaling is involved in the development of Barrett’s esophagus (BE), a precursor of esophageal adenocarcinoma (EAC). In various cancers, BMP4 has been found to induce epithelial-mesenchymal transition (EMT) but its function in the development of EAC is currently unclear. Aim To investigate the expression of BMP4 and several members of the BMP4 pathway in EAC. Additionally, to determine the effect of BMP4 signaling in a human Barrett’s esophagus (BAR-T) and adenocarcinoma (OE33) cell line. Methods Expression of BMP4, its downstream target ID2 and members of the BMP4 pathway were determined by Q-RT-PCR, immunohistochemistry and Western blot analysis using biopsy samples from EAC patients. BAR-T and OE33 cells were incubated with BMP4 or the BMP4 antagonist, Noggin, and cell viability and migration assays were performed. In addition, expression of factors associated with EMT (SNAIL2, CDH1, CDH2 and Vimentin) was evaluated by Q-RT-PCR and Western blot analysis. Results Compared to squamous epithelium (SQ), BMP4 expression was significantly upregulated in EAC and BE. In addition, the expression of ID2 was significantly upregulated in EAC and BE compared to SQ. Western blot analysis confirmed our results, showing an upregulated expression of BMP4 and ID2 in both BE and EAC. In addition, more phosphorylation of SMAD1/5/8 was observed. BMP4 incubation inhibited cell viability, but induced cell migration in both BAR-T and OE33 cells. Upon BMP4 incubation, SNAIL2 expression was significantly upregulated in BAR-T and OE33 cells while CDH1 expression was significantly downregulated. These results were confirmed by Western blot analysis. Conclusion Our results indicate active BMP4 signaling in BE and EAC and suggest that this results in an invasive phenotype by inducing an EMT-like response through upregulation of SNAIL2 and subsequent downregulation of CDH1. PMID:27191723
Preclinical Study of AUY922, a Novel Hsp90 Inhibitor, in the Treatment of Esophageal Adenocarcinoma.
Kosovec, Juliann E; Zaidi, Ali H; Kelly, Lori A; Rotoloni, Christina L; Vytlacil, Christopher; DiCarlo, Christina; Matsui, Daisuke; Komatsu, Yoshihiro; Boyd, Natalie H; Omstead, Ashten; Kolano, Elena L; Biederman, Robert W W; Finley, Gene; Silverman, Jan F; Landreneau, Rodney J; Jobe, Blair A
2016-08-01
To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo. EAC is a leading cause of cancer death, and current treatment options are limited. Hsp90, a chaperone protein that regulates several oncoproteins, is upregulated in EAC, and may be a novel target for therapy. In vitro, EAC cell lines were utilized to evaluate AUY922, alone and in combination with 5-fluorouracil (5-FU) and cisplatin. BrdU ELISA and flow cytometry were used to assess proliferation and measure apoptosis, respectively. Western blot and RT-PCR were performed to quantitate Hsp90 pathway expression. In vivo, esophagojejunostomy was performed on rats and treatment animals received AUY922 32 to 40 weeks postoperatively. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, gross histological evaluation, and Hsp90 pathway expression. In vitro, AUY922 demonstrated antiproliferative activity in both cell lines and showed enhanced efficacy with cisplatin and 5-FU. Western Blot and RT-PCR demonstrated downregulation of CDK1 and CDK4 and upregulation of Hsp72. In vivo, AUY922 showed decrease in tumor volume in 36.4% of rats (control = 9.4%), increase in 9.1% (control = 37.5%), and stable disease in 54.5% (control = 43.7%). Necropsy confirmed the presence of EAC in 50% of treatment animals and 75% of control animals. mRNA expression, pre- and posttreatment, demonstrated significant downregulation of MIF, Hsp70, Hsp90β, and CDK4, and upregulation of Hsp72. AUY922 exhibits antitumor efficacy in vitro and in vivo for EAC, suggesting the need for human clinical trials.
Han, Song; Lee, Constance W.; Trevino, Jose G.; Hughes, Steven J.; Sarosi, George A.
2013-01-01
Trypsin or Tumor associated trypsin (TAT) activation of Protease-activated receptor 2 (PAR-2) promotes tumor cell proliferation in gastrointestinal cancers. The role of the trypsin/PAR-2 network in esophageal adenocarcinoma (EA) development has not yet been investigated. The aim of this study is to investigate the role of trypsin/PAR-2 activation in EA tumorogenesis and therapy. We found that esophageal adenocarcinoma cells (EACs) and Barrett’s Metaplasia (BART) expressed high levels of type 3 extra-pancreatic trypsinogen (PRSS3), a novel type of TAT. Activity of secreted trypsin was detected in cultured media from EA OE19 and OE33 cultures but not from BART culture. Surface PAR-2 expression in BART and EACs was confirmed by both flow cytometry and immunofluorescence. Trypsin induced cell proliferation (∼ 2 fold; P<0.01) in all tested cell lines at a concentration of 10 nM. Inhibition of PAR-2 activity in EACs via the PAR-2 antagonist ENMD (500 µM), anti-PAR2 antibody SAM-11 (2 µg/ml), or siRNA PAR-2 knockdown, reduced cell proliferation and increased apoptosis by up to 4 fold (P<0.01). Trypsin stimulation led to phosphorylation of ERK1/2, suggesting involvement of MAPK pathway in PAR-2 signal transduction. Inhibition of PAR-2 activation or siRNA PAR-2 knockdown in EACs prior to treatment with 5 FU reduced cell viability of EACs by an additional 30% (P<0.01) compared to chemotherapy alone. Our data suggest that extra-pancreatic trypsinogen 3 is produced by EACs and activates PAR-2 in an autocrine manner. PAR-2 activation increases cancer cell proliferation, and promotes cancer cell survival. Targeting the trypsin activated PAR-2 pathway in conjunction with current chemotherapeutic agents may be a viable therapeutic strategy in EA. PMID:24146905
Kresty, Laura A.; Weh, Katherine M.; Zeyzus-Johns, Bree; Perez, Laura N.; Howell, Amy B.
2015-01-01
Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) were investigated utilizing acid-sensitive and acid-resistant human esophageal adenocarcinoma (EAC) cell lines and esophageal tumor xenografts in athymic NU/NU mice. C-PAC induced caspase-independent cell death mainly via autophagy and low levels of apoptosis in acid-sensitive JHAD1 and OE33 cells, but resulted in cellular necrosis in acid-resistant OE19 cells. Similarly, C-PAC induced necrosis in JHAD1 cells pushed to acid-resistance via repeated exposures to an acidified bile cocktail. C-PAC associated cell death involved PI3K/AKT/mTOR inactivation, pro-apoptotic protein induction (BAX, BAK1, deamidated BCL-xL, Cytochrome C, PARP), modulation of MAPKs (P-P38/P-JNK) and G2-M cell cycle arrest in vitro. Importantly, oral delivery of C-PAC significantly inhibited OE19 tumor xenograft growth via modulation of AKT/mTOR/MAPK signaling and induction of the autophagic form of LC3B supporting in vivo efficacy against EAC for the first time. C-PAC is a potent inducer of EAC cell death and is efficacious in vivo at non-toxic behaviorally achievable concentrations, holding promise for preventive or therapeutic interventions in cohorts at increased risk for EAC, a rapidly rising and extremely deadly malignancy. PMID:26378019
Bokisch, Viktor A.; Sobel, Alain T.
1974-01-01
This report describes receptors for C4b on human peripheral B lymphocytes. The simultaneous presence of C3b and C4b receptors on the same lymphocytes was demonstrated by the formation of mixed rosettes consisting of the lymphocytes, EAC14 and EAC1423. Furthermore, reduction of the number of EAC1423 rosette-forming lymphocytes in a lymphocyte population by albumin gradient centrifugation concomitantly reduced EAC14 rosette-forming lymphocytes. Binding of EAC14 intermediates to receptors on human lymphocytes and erythrocytes could be inhibited by equal amounts of soluble C3b or C4b, suggesting the presence of a single receptor for both ligands on those cells. In contrast, the results of the rosette assay with Raji cells, cultured human lymphoblastoid cells, EAC14 and EAC1423 suggested that the receptors for C4b and C3b are distinct entities, since Raji cells formed rosettes with EAC1423, but not with EAC14. Moreover, this report demonstrates a cooperation of erythrocyte-bound C4b and C3b in the binding of EAC1423 to B lymphocytes. In contrast to KAF-treated C3b, KAF-treated C4b did not bind to B lymphocytes, indicating that these cells lack a receptor for C4d. PMID:4547573
Bhattacharya, Shamik; Das, Tanaya; Biswas, Archita; Gomes, Aparna; Gomes, Antony; Dungdung, Sandhya Rekha
2013-11-01
BF-CT1, a 13 kDa protein isolated from Bungarus fasciatus snake venom through CM cellulose ion exchange chromatography at 0.02 M NaCl salt gradient showed cytotoxicity in in vitro and in vivo experimental models. In in vivo Ehrlich ascites carcinoma (EAC) induced BALB/c mice model, BF-CT1 treatment reduced EAC cell count significantly through apoptotic cell death pathway as evidenced by FACS analysis, increased caspase 3, 9 activity and altered pro, antiapoptotic protein expression. BF-CT1 treatment caused cell shrinkage, chromatin condensation and induced apoptosis through increased caspase 3, caspase 9 activity, PARP cleavage and down regulation of heat shock proteins in U937 leukemic cell line. Cytosolic cytochrome C production was increased after BF-CT1 treatment upon U937 cell line. BF-CT1 treated U937 cell showed cell cycle arrest at sub G1 phase through cyclin D and CDK down regulation with up regulation of p15 and p16. It also down regulated PI3K/AKT pathway and MAPkinase pathway and promoted apoptosis and regulated cell proliferation in U937 cells. BF-CT1 prevented angiogenesis in in vitro U937 cell line through decreased VEGF and TGF-β1 production. Copyright © 2013 Elsevier Ltd. All rights reserved.
Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas
Kuick, Rork; Thomas, Dafydd G.; Nadal, Ernest; Lin, Jules; Chang, Andrew C.; Reddy, Rishindra M.; Orringer, Mark B.; Taylor, Jeremy M. G.; Wang, Thomas D.; Beer, David G.
2016-01-01
The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies. PMID:27363029
Labhardt, Niklaus Daniel; Ringera, Isaac; Lejone, Thabo Ishmael; Cheleboi, Molisana; Wagner, Sarah; Muhairwe, Josephine; Klimkait, Thomas
2017-07-19
HIV-infected individuals on first-line antiretroviral therapy (ART) in resource-limited settings who do not achieve the last "90" (viral suppression) enter a complex care cascade: enhanced adherence counselling (EAC), repetition of viral load (VL) and switch to second-line ART aiming to achieve resuppression. This study describes the "failure cascade" in patients in Lesotho. Patients aged ≥16 years on first-line ART at 10 facilities in rural Lesotho received a first-time VL in June 2014. Those with VL ≥80 copies/mL were included in a cohort. The care cascade was assessed at four points: attendance of EAC, result of follow-up VL after EAC, switch to second-line in case of sustained unsuppressed VL and outcome 18 months after the initial unsuppressed VL. Multivariate logistic regression was used to assess predictors of being retained in care with viral resuppression at follow-up. Out of 1563 patients who underwent first-time VL, 138 (8.8%) had unsuppressed VL in June 2014. Out of these, 124 (90%) attended EAC and 116 (84%) had follow-up VL (4 died, 2 transferred out, 11 lost, 5 switched to second-line before follow-up VL). Among the 116 with follow-up VL, 36 (31%) achieved resuppression. Out of the 80 with sustained unsuppressed VL, 58 were switched to second-line, the remaining continued first line. At 18 months' follow-up in December 2015, out of the initially 138 with unsuppressed VL, 56 (41%) were in care and virally suppressed, 37 (27%) were in care with unsuppressed VL and the remaining 45 (33%) were lost, dead, transferred to another clinic or without documented VL. Achieving viral resuppression after EAC (adjusted odds ratio (aOR): 5.02; 95% confidence interval: 1.14-22.09; p = 0.033) and being switched to second-line in case of sustained viremia after EAC (aOR: 7.17; 1.90-27.04; p = 0.004) were associated with being retained in care and virally suppressed at 18 months of follow-up. Age, gender, education, time on ART and level of VL were not associated. In this study in rural Lesotho, outcomes along the "failure cascade" were poor. To improve outcomes in this vulnerable patient group who fails the last "90", programmes need to focus on timely EAC and switch to second line for cases with continuous viremia despite EAC.
The human adrenocortical carcinoma cell line H295R is being used as an in vitro steroidogenesis screening assay to assess the impact of endocrine active chemicals (EACs) capable of altering steroid biosynthesis. To enhance the interpretation and quantitative application of measur...
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Xiang, Jiayuan; Hu, Chen; Chen, Liying; Zhang, Dong; Ding, Ping; Chen, Dong; Liu, Hao; Chen, Jian; Wu, Xianzhang; Lai, Xiaokang
2016-10-01
The effect and mechanism of Zn(II) on improving the performances of lead-acid cell with electrochemical active carbon (EAC) in negative mass is investigated. The hydrogen evolution of the cell is significantly reduced due to the deposition of Zn on carbon surface and the increased porosity of negative mass. Zn(II) additives can also improve the low-temperature and high-rate capacities of the cell with EAC in negative mass, which ascribes to the formation of Zn on lead and carbon surface that constructs a conductive bridge among the active mass. Under the co-contribution of EAC and Zn(II), the partial-state-of-charge cycle life is greatly prolonged. EAC optimizes the NAM structure and porosity to enhance the charge acceptance and retard the lead sulfate accumulation. Zn(II) additive reduces the hydrogen evolution during charge process and improves the electric conductivity of the negative electrode. The cell with 0.6 wt% EAC and 0.006 wt% ZnO in negative mass exhibits 90% reversible capacity of the initial capacity after 2100 cycles. In contrast, the cell with 0.6 wt% EAC exhibits 84% reversible capacity after 2100 cycles and the control cell with no EAC and Zn(II) exhibits less than 80% reversible capacity after 1350 cycles.
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2012-02-21
... effective administration of Federal elections. DATES: Written comments must be submitted on or before 4 p.m... to [email protected] with Urban/Rural study as the subject line. Written comments on the proposed... free copy of the survey: (1) Access the EAC Web site at www.eac.gov ; (2) write to the EAC (including...
Testa, Ugo; Castelli, Germana; Pelosi, Elvira
2017-01-01
Esophageal cancer (EC) is the eighth most common cancer and is the sixth leading cause of death worldwide. The incidence of histologic subtypes of EC, esophageal adenocarcinoma (EAC) and esophageal squamous carcinoma (ESCC), display considerable geographic variation. EAC arises from metaplastic Barrett’s esophagus (BE) in the context of chronic inflammation secondary to exposure to acid and bile. The main risk factors for developing ESCC are cigarette smoking and alcohol consumption. The main somatic genetic abnormalities showed a different genetic landscape in EAC compared to ESCC. EAC is a heterogeneous cancer dominated by copy number alterations, a high mutational burden, co-amplification of receptor tyrosine kinase, frequent TP53 mutations. The cellular origins of BE and EAC are still not understood: animal models supported a cellular origin either from stem cells located in the basal layer of esophageal epithelium or from progenitors present in the cardia region. Many studies support the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. The exact identification of these CSCs, as well as their role in the pathogenesis of EAC and ESCC remain still to be demonstrated. The reviewed studies suggest that current molecular and cellular characterization of EAC and ESCC should serve as background for development of new treatment strategies. PMID:28930282
Momordica charantia seed lectin: toxicity, bacterial agglutination and antitumor properties.
Kabir, Syed Rashel; Nabi, Md Mahamodun; Nurujjaman, Md; Abu Reza, Md; Alam, A H M Khurshid; Uz Zaman, Rokon; Khalid-Bin-Ferdaus, Khandaker Md; Amin, Ruhul; Khan, Md Masudul Hasan; Hossain, Md Anowar; Uddin, Md Salim; Mahmud, Zahid Hayat
2015-03-01
In last three decades, several studies were carried out on the D-galactose-specific lectin of Momordica charantia seeds (MCL). In the present study, in vitro growth inhibition (8-23 %) at different concentrations (6-24 μg/ml) of MCL was observed against Ehrlich ascites carcinoma (EAC) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MCL also showed 28, 45, and 75 % growth inhibitions against EAC cells when administered 1.2, 2.0, and 2.8 mg/kg/day (i.p.), respectively for five consequent days in vivo in mice. After lectin treatment, the level of red blood cell and hemoglobin was increased significantly with the decrease of white blood cell and maintained the normal level when compared with EAC-bearing control and normal mice without EAC cells. Although MCL caused cell cycle arrest at G0/G1 phase of EAC cells, any irregular shape or apoptotic morphological alterations in the lectin-treated EAC cells was not observed by an optical and fluorescence microscope. Lectin showed toxicity against brine shrimp nauplii with an LC50 value of 49.7 μg/ml. Four out of seven pathogenic bacteria were agglutinated by MCL in the absence of inhibitory sugar D-lactose/D-galactose. In conclusion, MCL showed strong cytotoxic effect and therefore can be used as a potent anticancer chemotherapeutic agent.
Kosovec, Juliann E; Zaidi, Ali H; Omstead, Ashten N; Matsui, Daisuke; Biedka, Mark J; Cox, Erin J; Campbell, Patrick T; Biederman, Robert W W; Kelly, Ronan J; Jobe, Blair A
2017-11-21
Esophageal adenocarcinoma (EAC) is a deadly disease with limited therapeutic options. In the present study, we determined the preclinical efficacy of CDK4/6 inhibitor abemaciclib for treatment of EAC. In vitro , apoptosis, proliferation, and pathway regulation were evaluated in OE19, OE33, and FLO1 EAC cell lines. In vivo , esophagojejunostomy was performed on rats to induce EAC. At 36 weeks post-surgery, MRI and endoscopic biopsy established baseline tumor volume and molecular correlates, respectively. Next, the study animals were randomized to 26mg/kg intraperitoneal abemaciclib treatment or vehicle control for 28 days. Pre and post treatment MRIs, histopathology, and qRT-PCR were utilized to determine response. Our results demonstrated treatment with abemaciclib lead to increased apoptosis, and decreased proliferation in OE19 (p=0.185), OE33 (p=0.048), and FLO1 (p=0.043) with anticipated downstream molecular inhibition. In vivo , 78.9% of treatment animals demonstrated >20% tumor volume decrease (placebo 0%). Mean tumor volume changed in the treatment arm by -65.5% (placebo +133.5%) (p<0.01), and prevalence changed by -37.5% (placebo +16.7%) (p<0.01). Pre vs post treatment qRT-PCR demonstrated significant inhibition of all downstream molecular correlates. Overall our findings suggest potent antitumor efficacy of abemaciclib against EAC with evident molecular pathway inhibition and reasonable safety, establishing the rationale for future clinical development.
Hartmans, Elmire; Linssen, Matthijs D; Sikkens, Claire; Levens, Afra; Witjes, Max J H; van Dam, Gooitzen M; Nagengast, Wouter B
2017-05-02
Esophageal carcinoma (EC) is a global health problem, with disappointing 5-year survival rates of only 15-25%. Near-infrared targeted photodynamic therapy (NIR-tPDT) is a novel strategy in which cancer-targeted phototoxicity is able to selectively treat malignant cells. In this in vitro report we demonstrate the applicability of antibody-based NIR-tPDT in esophageal adenocarcinoma (EAC), using the phototoxic compounds cetuximab-IRDye700DX and trastuzumab-IRDye700DX, targeting respectively epidermal growth factor receptor 1 (EGFR) and 2 (HER2). Furthermore, we demonstrate that NIR-tPDT can be made more effective by tyrosine kinase inhibitor (TKI) induced growth receptor upregulation. Together, these results unveil a novel strategy for non-invasive EAC treatment, and by pretreatment-induced receptor upregulation its future clinical application may be optimized.
Enabling the On-line Intrinsic Evolution of Analog Controllers
NASA Technical Reports Server (NTRS)
Gwaltney, David A.; Ferguson, Michael I.
2005-01-01
The intrinsic evolution of analog controllers to provide closed-loop control of the speed of a DC motor has been previously demonstrated at NASA Marshall Space Flight Center. A side effect of the evolutionary process is that during evolution there are necessarily poor configurations to be evaluated that could cause damage to the plant, This paper concerns the development and implementation of a safe Evolvable Analog Controller (EAC) architecture able to evolve controllers on-line even in the presence of these poor configurations, The EAC concept is discussed and experimental results are presented that show the feasibility of the approach This EAC architecture represents the first in a series of steps required to make deployment of an evolvable controller a reality.
Enabling the On-Line Intrinsic Evolution of Analog Controllers
NASA Technical Reports Server (NTRS)
Gwaltney, David A.; Ferguson, Michael I.
2005-01-01
The intrinsic evolution of analog controllers to provide closed-loop control of the speed of a DC motor has been previously demonstrated at NASA Marshall Space Flight Center. A side fleet of the evolutionary process is that during evolution there are necessarily poor configurations to be evaluated that could cause damage to the plant. This paper concern the development and implementation of a safe Evolvable Analog Controller (EAC) architecture able to evolve controllers on-line even in the presence of these poor configurations. The EAC concept is discussed and experimental results are presented that show the feasibility of the approach This EAC architecture represents the first in a series of steps required to make deployment of an evolvable controller a reality.
PGE from Octopus aegina Induces Apoptosis in Ehrlich's Ascites Carcinoma of Mice.
Karthigayan, S; Balasubashini, M Sri; Balasubramanian, T; Somasundaram, S T
2007-01-01
ABSTRACT The present study was carried out to assess the antitumor effect of venomous peptide from the cephalopod Octopus aegina on Ehrlich's ascites carcinoma (EAC). Male albino Swiss mice were used in the present study. Four groups of animals were treated with three doses of the sublethal dose of venom, 15, 75, and 150 mug/kg body weight (intraperitoneal injection), along with the standard drug 5-fluorouracil (20 mg/kg b.w.). After 10 days of treatment, six animals from each group were sacrificed for the biochemical analysis and the rest were left to calculate the mean survival time. In EAC-bearing mice, mean lifespan, tumor volume, hemoglobin, red blood cells, and lymphocytes were significantly decreased when compared to the normal animals. While body weight, neutrophils, and viable tumor cell count were increased in the EAC-bearing mice, these changes were brought back to near normal levels in different treatment groups. The macromolecule concentration of peritoneal cells, such as DNA, RNA, and protein, were altered in the EAC-bearing mice and observed to be near normal in the treatment groups. The caspase-3 activity was significantly increased in the peritoneal cells of the treatment groups when compared to the EAC-bearing mice. The role of apoptotic cascade in EAC cell death was confirmed by the DNA fragmentation on agarose gel. Apart from the antitumor effect, octopus venom reduced the tumor burden on the liver and altered the changes in the activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Therefore, the venom from O. aegina has a potential antitumor effect on the EAC-bearing mice.
To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC ...
Chakraborty, Tridib; Bhuniya, Dipak; Chatterjee, Mary; Rahaman, Mosiur; Singha, Dipak; Chatterjee, Baidya Nath; Datta, Subrata; Rana, Ajay; Samanta, Kartick; Srivastawa, Sunil; Maitra, Sankar K; Chatterjee, Malay
2007-12-28
To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)-bearing murine model. Male Swiss albino mice were divided into four groups: Group A was the untreated normal control; Group B was the EAC control mice group that received serial, intraperitoneal (ip) inoculations of rapidly proliferating 2 x 10(5) viable EAC cells in 0.2 mL of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract (ALE) of the plant at a dose of 2.5 mg/kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tumour inoculation (ALE control); and Group D was the EAC + ALE-treatment group. The chemopreventive potential of the ALE was evaluated in a murine model by studying various biological parameters and genotoxic markers, such as tumour cell count, mean survival of the animals, haematological indices, hepatocellular histology, immunohistochemical expression of liver metallothionein (MT) protein, sister-chromatid exchanges (SCEs), and DNA alterations. Treatment of the EAC-bearing mice with the ALE significantly (P < 0.001) reduced viable tumour cell count by 68.34% (228.7 x 10(6) +/- 0.53) when compared to EAC control mice (72.4 x 10(6) +/- 0.49), and restored body and organ weights almost to the normal values. ALE administration also increased (P < 0.001) mean survival of the hosts from 35 +/- 3.46 d in EAC control mice to 83 +/- 2.69 d in EAC + ALE-treated mice. Haematological indices also showed marked improvement with administration of ALE in EAC-bearing animals. There was a significant increase in RBC count (P < 0.001), hemoglobin percent (P < 0.001), and haematocrit value (P < 0.001) from 4.3 +/- 0.12, 6.4 +/- 0.93, and 17.63 +/- 0.72 respectively in EAC control mice to 7.1 +/- 0.13, 12.1 +/- 0.77, and 30.23 +/- 0.57 respectively in EAC + ALE-treated group, along with concurrent decrement (P < 0.001) in WBC count from 18.8 +/- 0.54 in EAC control to 8.4 +/- 0.71 in EAC + ALE. Furthermore, treatment with ALE substantially improved hepatocellular architecture and no noticeable neoplastic lesions or foci of cellular alteration were observed. Daily administration of the ALE was found to limit liver MT expression, an important marker of cell proliferation with concomitant reduction in MT immunoreactivity (62.25 +/- 2.58 vs 86.24 +/- 5.69, P < 0.01). ALE was also potentially effective in reducing (P < 0.001) the frequency of SCEs from 14.94 +/- 2.14 in EAC control to 5.12 +/- 1.16 in EAC + ALE-treated group. Finally, in comparison to the EAC control, ALE was able to suppress in vivo DNA damage by abating the generations of 'tailed' DNA by 53.59% (98.65 +/- 2.31 vs 45.06 +/- 1.14, P < 0.001), and DNA single-strand breaks (SSBs) by 38.53% (3.14 +/- 0.31 vs 1.93 +/- 0.23, P < 0.01) in EAC-bearing murine liver. Our data indicate that, ALE is beneficial in restoring haematological and hepatic histological profiles and in lengthening the survival of the animals against the proliferation of ascites tumour in vivo. Finally, the chemopreventive efficacy of the ALE is manifested in limiting MT expression and in preventing DNA alterations in murine liver. The promising results of this study suggest further investigation into the chemopreventive mechanisms of the medicinal plant A. ilicifolius in vivo and in vitro.
Boric acid enhances in vivo Ehrlich ascites carcinoma cell proliferation in Swiss albino mice.
Qureshi, S; Al-Shabanah, O A; Al-Harbi, M M; Al-Bekairi, A M; Raza, M
2001-08-13
The influence of boric acid, a boron carrier, on Ehrlich ascites carcinoma (EAC) cell-bearing mice was investigated in view of its importance in the boron neutron capture therapy and the influence of boron on proliferation and progression of cancer cells mediated by proteoglycans and collagen. The present study included the evaluation of boric acid for the effects on total count and viability of EAC cells in addition to their non-protein sulfhydryls (NP-SH) and malondialdehyde (MDA) contents as parameters for conjugative detoxication potency and possible oxidative damage. The EAC cell-bearing animals were also observed for the effect on survival, body weight changes, and histopathological evaluation of the tumors grown at the site of inoculation. The treatment with boric acid significantly increased the total number of peritoneal EAC cells and their viability. A significant increase in the body weight was observed that dose-dependently reached plateau levels by 20 days of treatment. Conversely, a reduction in the duration of survival of these animals was evident with the same protocol. Boric acid treatment resulted in a decrease in NP-SH contents with a concomitant increase in MDA levels in EAC cells as revealed by the results of the biochemical analysis. These data are supported by our results on histopathological investigations, which apparently showed fast growth, in addition to several mitotic figures and mixed inflammatory reaction, after treatment with boric acid. It seems likely that a particular combination of properties of boric acid, rather than a single characteristic alone, will provide useful information on the use of this boron carrier in neutron capture therapy.
Evaluation of fluoren-NU as a novel antitumor agent.
Mukherjee, Asama; Dutta, Sushanta; Chashoo, Gousia; Bhagat, Madhulika; Saxena, Ajit Kumar; Sanyal, Utpal
2009-01-01
A new nitrososourea derivative, namely fluoren-NU, 3-[2-(3-(2-chloroethyl)-3-nitrosouriedo}ethyl]-spiro[5,9'-fluorenyl]imidazolidine-2,4-dione (compound 2e), was synthesized from 3-(2-bromoethyl)-spiro [5,9'-fluorenyl]imidazolidine-2,4-dione via a four-step synthetic procedure. Its chemical alkylating activity was assessed by coupling with 4-(4-nitrobenzyl)pyridine. In vitro screening in six human tumor cell lines, namely SK-N-SH CNS, IMR-32 neuroblastoma, A549 lung, DU-145 prostate, HL-60 leukemia, and U-937 lymphoma, revealed its significant cytotoxicity in SK-N-SH. Its in vivo antitumoral potency was assessed in murine ascites tumors Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice. Results revealed significant tumor regression effects in both of these tumors. Life span of mice bearing advanced tumor for 5 days before the drug challenge was also considerably increased. In vivo toxicological assay at its optimum dose of 40 mg/kg for days 1-7 treatment schedule was conducted sequentially on day 9, 14, and 19 in normal and EAC-bearing mice. Results revealed that it did not adversely affect hematopoiesis or exhibit drug-induced hepatotoxicity and nephrotoxicity. It has shown minimal cytotoxic effect on human peripheral blood mononuclear cells (PBMC) having a high IC50 value of 792 microM. Compared to Mitonafide and CCNU used as standards it also significantly inhibited DNA and RNA synthesis in EAC tumor cells in vitro at 8 microM concentration.
Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential
ALAM, BADRUL; MAJUMDER, RAJIB; AKTER, SHAHINA; LEE, SANG-HAN
2015-01-01
The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (P<0.05). Hematological and serum biochemical profiles were restored to normal levels in the extract-treated mice compared with the EAC control mice. MPBL and EPBL treatment significantly decreased lipid peroxidation (P<0.05) and restored GSH, SOD and CAT levels towards normal compared with the EAC control. Taken together, the results of the present study demonstrated that Piper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential. PMID:25624910
Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.
Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han
2015-02-01
The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (P<0.05). Hematological and serum biochemical profiles were restored to normal levels in the extract-treated mice compared with the EAC control mice. MPBL and EPBL treatment significantly decreased lipid peroxidation (P<0.05) and restored GSH, SOD and CAT levels towards normal compared with the EAC control. Taken together, the results of the present study demonstrated that Piper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.
Islam, Farhadul; Ali, Shaikh Mohummad Mohsin; Khanam, Jahan Ara
2013-01-01
Objective To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice. Methods Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed. Results The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC. Conclusions ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice. PMID:23593588
Mhawech-Fauceglia, Paulette; Wang, Dan; Kesterson, Joshua; Syriac, Susanna; Clark, Kimberly; Frederick, Peter J; Lele, Shashikant; Liu, Song
2011-03-23
Endometrial cancer is the most common gynecologic malignancy in the developed countries. Clinical studies have shown that early stage uterine serous carcinoma (USC) has outcomes similar to early stage high grade endometrioid adenocarcinoma (EAC-G3) than to early stage low grade endometrioid adenocarcinoma (EAC-G1). However, little is known about the origin of these different clinical outcomes. This study applied the whole genome expression profiling to explore the expression difference of stage I USC (n = 11) relative to stage I EAC-G3 (n = 11) and stage I EAC-G1 (n = 11), respectively. We found that the expression difference between USC and EAC-G3, as measured by the number of differentially expressed genes (DEGs), is consistently less than that found between USC and EAC-G1. Pathway enrichment analyses suggested that DEGs specific to USC vs. EAC-G3 are enriched for genes involved in signaling transduction, while DEGs specific to USC vs. EAC-G1 are enriched for genes involved in cell cycle. Gene expression differences for selected DEGs are confirmed by quantitative RT-PCR with a high validation rate. This data, although preliminary, indicates that stage I USC is genetically similar to stage I EAC-G3 compared to stage I EAC-G1. DEGs identified from this study might provide an insight in to the potential mechanisms that influence the clinical outcome differences between endometrial cancer subtypes. They might also have potential prognostic and therapeutic impacts on patients diagnosed with uterine cancer.
Shimoyama, Tadashi; Chinda, Daisuke; Sawada, Yoshihiko; Komai, Kazuo; Chiba, Hironobu; Saito, Yoshiharu; Sasaki, Yoshio; Matsuzaka, Masashi; Fukuda, Shinsaku
2017-01-01
Objective CYP2C19 metabolic activity influences the efficacy of Helicobacter pylori eradication therapies comprising PPIs. Rabeprazole (RPZ) and esomeprazole (EPZ) are PPIs not extensively metabolized by CYP2C19. The aim of this study was to elucidate whether or not first-line triple therapies using RPZ or EPZ are equally effective in Japanese patients with different CYP2C19 genotypes. Methods Two-hundred patients infected with H. pylori were randomized to receive one of the following regimens: amoxicillin (750 mg), clarithromycin (200 mg), and either esomeprazole (20 mg) (EAC group) or rabeprazole (10 mg) (RAC group), twice a day for one week. The CYP2C19 polymorphisms were determined by polymerase chain reaction and the serum level of pepsinogens was measured. Results The eradication rates of the EAC and RAC regimens were 79.8% (95% confidential interval: 71.7-89.0%) and 74.7% (66.0-83.4%), respectively, in a per protocol (PP) analysis (p=0.488). The eradication rates of the EAC and RAC regimens were not significantly different between patients with the homo EM genotype (p=0.999) or hetero IM or PM genotypes (p=0.286). A lower PG I/II ratio was associated with lower eradication rates (p=0.025). Conclusion Although the eradication rate was less than 80%, the EAC and RAC regimens were equally effective in each CYP2C19 genotype group. The PG I/II ratio was associated with the results of EAC and RAC therapy in this series of patients.
Shimoyama, Tadashi; Chinda, Daisuke; Sawada, Yoshihiko; Komai, Kazuo; Chiba, Hironobu; Saito, Yoshiharu; Sasaki, Yoshio; Matsuzaka, Masashi; Fukuda, Shinsaku
2017-01-01
Objective CYP2C19 metabolic activity influences the efficacy of Helicobacter pylori eradication therapies comprising PPIs. Rabeprazole (RPZ) and esomeprazole (EPZ) are PPIs not extensively metabolized by CYP2C19. The aim of this study was to elucidate whether or not first-line triple therapies using RPZ or EPZ are equally effective in Japanese patients with different CYP2C19 genotypes. Methods Two-hundred patients infected with H. pylori were randomized to receive one of the following regimens: amoxicillin (750 mg), clarithromycin (200 mg), and either esomeprazole (20 mg) (EAC group) or rabeprazole (10 mg) (RAC group), twice a day for one week. The CYP2C19 polymorphisms were determined by polymerase chain reaction and the serum level of pepsinogens was measured. Results The eradication rates of the EAC and RAC regimens were 79.8% (95% confidential interval: 71.7-89.0%) and 74.7% (66.0-83.4%), respectively, in a per protocol (PP) analysis (p=0.488). The eradication rates of the EAC and RAC regimens were not significantly different between patients with the homo EM genotype (p=0.999) or hetero IM or PM genotypes (p=0.286). A lower PG I/II ratio was associated with lower eradication rates (p=0.025). Conclusion Although the eradication rate was less than 80%, the EAC and RAC regimens were equally effective in each CYP2C19 genotype group. The PG I/II ratio was associated with the results of EAC and RAC therapy in this series of patients. PMID:28674348
Mhawech-Fauceglia, Paulette; Wang, Dan; Kesterson, Joshua; Syriac, Susanna; Clark, Kimberly; Frederick, Peter J.; Lele, Shashikant; Liu, Song
2011-01-01
Background Endometrial cancer is the most common gynecologic malignancy in the developed countries. Clinical studies have shown that early stage uterine serous carcinoma (USC) has outcomes similar to early stage high grade endometrioid adenocarcinoma (EAC-G3) than to early stage low grade endometrioid adenocarcinoma (EAC-G1). However, little is known about the origin of these different clinical outcomes. This study applied the whole genome expression profiling to explore the expression difference of stage I USC (n = 11) relative to stage I EAC-G3 (n = 11) and stage I EAC-G1 (n = 11), respectively. Methodology/Principal Finding We found that the expression difference between USC and EAC-G3, as measured by the number of differentially expressed genes (DEGs), is consistently less than that found between USC and EAC-G1. Pathway enrichment analyses suggested that DEGs specific to USC vs. EAC-G3 are enriched for genes involved in signaling transduction, while DEGs specific to USC vs. EAC-G1 are enriched for genes involved in cell cycle. Gene expression differences for selected DEGs are confirmed by quantitative RT-PCR with a high validation rate. Conclusion This data, although preliminary, indicates that stage I USC is genetically similar to stage I EAC-G3 compared to stage I EAC-G1. DEGs identified from this study might provide an insight in to the potential mechanisms that influence the clinical outcome differences between endometrial cancer subtypes. They might also have potential prognostic and therapeutic impacts on patients diagnosed with uterine cancer. PMID:21448288
Mallick, Md Nasar; Khan, Washim; Parveen, Rabea; Ahmad, Sayeed; Sadaf; Najm, Mohammad Zeeshan; Ahmad, Istaq; Husain, Syed Akhtar
2017-10-01
Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells. This work investigated anticancer activity of bioactive fraction of BM. The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water. The in vitro anticancer activity was performed against various Human Cancer Cell lines, namely, Colon (HT29, Colo320, and Caco2), Lung (A549), Cervix (HeLa, SiHa), and Breast (MCF-7, MDAMB-231). Further, DCM fraction was evaluated in vivo for anticancer activity against Ehrlich ascites carcinoma (EAC) tumor-bearing mice since it showed the best cytotoxicity at 72 h (IC 50 41.0-60.0 µg/mL). The metabolic fingerprinting of these extract were carried out using high-performance thin-layer chromatography along with quantification of bacoside A, bacoside B, cucurbitacin B, cucurbitacin E, and bittulinic acid. Oral administration of DCM fraction at a dose of 40 mg/kg rendered prominent reduction of tumor regression parameters such as tumor weight, packed cell volume, tumor volume and viable tumor cell count as compared to the untreated mice of the EAC control group. The anticancer activity of DCM fraction may be due to the presence of large amount of bacoside A, B and cucurbitacins. The molecular docking studies of major metabolites with targeted proteins predicted the anticancer activity of DCM fraction which was in support of in vivo activity. The in vitro , in vivo , analytical and in silico studies on DCM fraction of Bacopa monieri has proved its great potential for development of anticancer phytopharmaceuticals. A new HPTLC method has been developed and validated for the qualitative and quantitative analysis of bacoside A, B, cucurbitacin B, D, E and bittulinic acid in Bacopa monnieri extract. Enrichment of active anticancer metabolites was done by polarity based fractionations of hydroalcoholic extract of Bacopa. DCM fraction of a hydroalcoholic extract of Bacopa showed anticancer potential against human cancer cell line (IC50 41.0-60.0 µg/mL) and in EAC treated mice (at a dose of 40 mg/kg body weight). The anticancer activity of Bacopa may be due to the presence of bacosides and cucurbitacin and it was confirmed by in silico screening. Abbreviations used: DBM: DCM fraction of Bacopa monnieri; DCM: Dichloromethane; EAC: Ehrlich ascites carcinoma; HCT: Hematocrit; HGB: Hemoglobin; HPTLC: High performance thin layer chromatography; ICH: International council for Harmonisation; LOD: Limit of detection; LOQ: Limit of quantification; LYM: Lymphocytes; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular haemoglobin concentration (MCHC); MCV: Mean corpuscular volume; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PLT: Platelet; RBC: Red blood cell; RDW: Red blood cell distribution width; RSD: Relative standard deviation; WBC: White blood cells.
Mallick, Md. Nasar; Khan, Washim; Parveen, Rabea; Ahmad, Sayeed; Sadaf; Najm, Mohammad Zeeshan; Ahmad, Istaq; Husain, Syed Akhtar
2017-01-01
Background: Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells. Objectives: This work investigated anticancer activity of bioactive fraction of BM. Materials and Methods: The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water. The in vitro anticancer activity was performed against various Human Cancer Cell lines, namely, Colon (HT29, Colo320, and Caco2), Lung (A549), Cervix (HeLa, SiHa), and Breast (MCF-7, MDAMB-231). Further, DCM fraction was evaluated in vivo for anticancer activity against Ehrlich ascites carcinoma (EAC) tumor-bearing mice since it showed the best cytotoxicity at 72 h (IC50 41.0–60.0 µg/mL). The metabolic fingerprinting of these extract were carried out using high-performance thin-layer chromatography along with quantification of bacoside A, bacoside B, cucurbitacin B, cucurbitacin E, and bittulinic acid. Results: Oral administration of DCM fraction at a dose of 40 mg/kg rendered prominent reduction of tumor regression parameters such as tumor weight, packed cell volume, tumor volume and viable tumor cell count as compared to the untreated mice of the EAC control group. The anticancer activity of DCM fraction may be due to the presence of large amount of bacoside A, B and cucurbitacins. The molecular docking studies of major metabolites with targeted proteins predicted the anticancer activity of DCM fraction which was in support of in vivo activity. Conclusion: The in vitro, in vivo, analytical and in silico studies on DCM fraction of Bacopa monieri has proved its great potential for development of anticancer phytopharmaceuticals. SUMMARY A new HPTLC method has been developed and validated for the qualitative and quantitative analysis of bacoside A, B, cucurbitacin B, D, E and bittulinic acid in Bacopa monnieri extract. Enrichment of active anticancer metabolites was done by polarity based fractionations of hydroalcoholic extract of Bacopa. DCM fraction of a hydroalcoholic extract of Bacopa showed anticancer potential against human cancer cell line (IC50 41.0-60.0 µg/mL) and in EAC treated mice (at a dose of 40 mg/kg body weight). The anticancer activity of Bacopa may be due to the presence of bacosides and cucurbitacin and it was confirmed by in silico screening. Abbreviations used: DBM: DCM fraction of Bacopa monnieri; DCM: Dichloromethane; EAC: Ehrlich ascites carcinoma; HCT: Hematocrit; HGB: Hemoglobin; HPTLC: High performance thin layer chromatography; ICH: International council for Harmonisation; LOD: Limit of detection; LOQ: Limit of quantification; LYM: Lymphocytes; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular haemoglobin concentration (MCHC); MCV: Mean corpuscular volume; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PLT: Platelet; RBC: Red blood cell; RDW: Red blood cell distribution width; RSD: Relative standard deviation; WBC: White blood cells. PMID:29142420
Pang, Chunhong; LaLonde, Amy; Godfrey, Tony E; Que, Jianwen; Sun, Jun; Wu, Tong Tong; Zhou, Zhongren
2017-01-01
Bile acid reflux in the esophagus plays an important role in the carcinogenesis of esophageal adenocarcinoma (EAC). The G-protein coupled bile acid receptor (TGR5) has been associated with the development of gastrointestinal cancer. However, little is known regarding the role of TGR5 in esophageal carcinoma and precancerous lesions. We analyzed genomic DNA from 116 EACs for copy number aberrations via Affymetrix SNP6.0 microarrays. The TGR5 gene locus was amplified in 12.7% (14/116) of the EACs. The TGR5 protein expression was also assessed using immunohistochemistry from tissue microarrays, including Barrett’s esophagus (BE), low-(LGD) and high-grade dysplasia (HGD), columnar cell metaplasia (CM), squamous epithelium (SE), EAC and squamous cell carcinoma. The TGR5 protein was highly expressed in 71% of EAC (75/106), 100% of HGD (11/11), 72% of LGD (13/18), 66% of BE (23/35), 84% of CM (52/62), and 36% of SE (30/83). The patients with high expression of TGR5 exhibited significantly worse overall survival compared to the patients with nonhigh expression. TGR5 high expression was significantly increased in the males compared to the females in all cases with an odds ratio of 1.9 times. The vitamin D receptor (VDR) was significantly correlated with TGR5 expression. Our findings indicated that TGR5 may play an important role in the development and prognosis of EAC through a bile acid ligand. Gender differences in TGR5 and VDR expression may explain why males have a higher incidence of EAC compared to females. PMID:28223834
Guilleret, Isabelle; Losi, Lorena; Chelbi, Sonia T; Fonda, Sergio; Bougel, Stéphanie; Saponaro, Sara; Gozzi, Gaia; Alberti, Loredana; Braunschweig, Richard; Benhattar, Jean
2016-10-14
Most types of cancer cells are characterized by aberrant methylation of promoter genes. In this study, we described a rapid, reproducible, and relatively inexpensive approach allowing the detection of multiple human methylated promoter genes from many tissue samples, without the need of bisulfite conversion. The Methylation Ligation-dependent Macroarray (MLM), an array-based analysis, was designed in order to measure methylation levels of 58 genes previously described as putative biomarkers of cancer. The performance of the design was proven by screening the methylation profile of DNA from esophageal cell lines, as well as microdissected formalin-fixed and paraffin-embedded (FFPE) tissues from esophageal adenocarcinoma (EAC). Using the MLM approach, we identified 32 (55%) hypermethylated promoters in EAC, and not or rarely methylated in normal tissues. Among them, 21promoters were found aberrantly methylated in more than half of tumors. Moreover, seven of them (ADAMTS18, APC, DKK2, FOXL2, GPX3, TIMP3 and WIF1) were found aberrantly methylated in all or almost all the tumor samples, suggesting an important role for these genes in EAC. In addition, dysregulation of the Wnt pathway with hypermethylation of several Wnt antagonist genes was frequently observed. MLM revealed a homogeneous pattern of methylation for a majority of tumors which were associated with an advanced stage at presentation and a poor prognosis. Interestingly, the few tumors presenting less methylation changes had a lower pathological stage. In conclusion, this study demonstrated the feasibility and accuracy of MLM for DNA methylation profiling of FFPE tissue samples. Copyright © 2016 Elsevier Inc. All rights reserved.
Habib, Muhammad Rowshanul; Karim, Muhammad Rezaul
2012-12-01
The objective of the study is to explore the anticancer activity of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea flower against Ehrlich ascites carcinoma cells (EAC) in Swiss albino mice. The activity of DEHP was evaluated at doses of 10, 20 and 40 mg kg-1 body mass applied intraperitoneally. DEHP showed a significant decrease in viable cell count (p < 0.05), mass gain (due to tumour burden) and elevated the life span of EAC cell bearing mice. Altered hematological profiles such as RBC, hemoglobin, WBC and differential count were reverted to normal levels in DEHP-treated mice. DEHP also brought back altered biochemical parameters (glucose, cholesterol, triglycerides, blood urea, SALP and SGOT) to normal level. Results of this study indicate that DEHP show potent dose dependent antitumour activity against EAC in vivo.
Dotsenko, E K; Goncharova, V A; Kuzubova, N A; Kamenova, M Iu; Egorova, N V
2008-01-01
To study biochemical composition of expired air condensate (EAC) in patients with chronic obstructive pulmonary disease (COPD) in relation to a phase and severity of the disease and its treatment. EAC was investigated in 18 COPD patients and 9 healthy subjects. Basic broncholytic therapy with ipratropium bromide was combined with beclomethasone and fenspiride in 11 and 7 patients, respectively. The condensate was lyophilised, the residue was solved and analysed on the biochemical analyzer Casis (Beringer Manheim, Rosch). EAC was examined for albumin, C-reactive protein, glucose, cholesterol, triglycerides, urea, uric acid, alkaline phosphatase (AP), lactate dehydrogenase, gamma-glutamyl transferase, total calcium, magnesium. Compared to healthy subjects, COPD patients' EAC contains significantly higher levels of albumin, C-reactive protein, calcium, bilirubin and more active AP. Quantitative composition of EAC depends on COPD phase and severity. A negative correlation exists between FEV+AEA-1 and albumin concentration, FEV+AEA-1 and CRP concentration. The anti-inflammatory therapy decreases EAC content of both protein and lipid metabolism products, enzyme activity reflecting attenuation of oxidant and inflammatory processes, stabilization of cell membranes in the respiratory zone. EAC composition reflects metabolic processes in the lungs and can be used for assessment of airway affection, activity of the inflammatory process and COPD treatment efficacy.
Kashio, Akinori; Sakamoto, Takashi; Karino, Shotaro; Kakigi, Akinobu; Iwasaki, Shinichi; Yamasoba, Tatsuya
2015-01-01
To predict round window niche (RWN) visibility using high-resolution computed tomography (HRCT). Case series with chart review. Academic tertiary care center. We retrospectively reviewed 70 cochlear implant ears that underwent presurgical axial HRCT with a surgical video recorder. The visibility of the RWN was classified into three types: 17 as invisible or nearly invisible, 22 as partially visible, and 31 as fully visible. Next, we measured the following three radiologic parameters: 1) the angle of the external auditory canal (EAC) relative to the cochlear basal turn, 2) the width of the facial recess, and 3) the relative location of the facial nerve (FN) to the cochlear basal turn. These were compared with the RWN visibility. Subsequently, to predict the RWN visibility, a line was created parallel to the EAC line and along the anterior lateral FN. The location of the line relative to the round window membrane was compared with the RWN view. In cases that had poor RWN visibility, the angle of the posterior canal wall portion of the EAC relative to the cochlear basal turn was significantly smaller and the location of the FN to the cochlear basal turn was closer. The location of the prediction line to the round window membrane highly predicted the RWN view during the surgery. The RWN visibility and the preoperative HRCT findings showed a high correlation. Drawing the prediction line is a simple and useful way for preoperatively predicting the RWN visibility in cochlear implant surgery.
Galvin, Karen C; Conroy, Melissa J; Doyle, Suzanne L; Dunne, Margaret R; Fahey, Ronan; Foley, Emma; O'Sullivan, Katie E; Doherty, Derek G; Geoghegan, Justin G; Ravi, Narayanasamy; O'Farrelly, Cliona; Reynolds, John V; Lysaght, Joanne
2018-04-01
Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continues to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression or proliferation, but transiently increased CD107a expression by CD8 + T cells. Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post neoadjuvant chemoradiotherapy, suggesting that combination with specific conventional treatments may severely impair the efficacy of anti-PD-1 immunotherapy. This study provides evidence that systemically administered anti-PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated inflammation outside the tumor in obesity-associated cancers, such as EAC. Furthermore, our data suggests that studies are required to identify the negative impact of concomitant therapies on PD-1 expression in order to boost overall response rates. Copyright © 2018 Elsevier B.V. All rights reserved.
Doblin, Martina A; Petrou, Katherina; Sinutok, Sutinee; Seymour, Justin R; Messer, Lauren F; Brown, Mark V; Norman, Louiza; Everett, Jason D; McInnes, Allison S; Ralph, Peter J; Thompson, Peter A; Hassler, Christel S
2016-01-01
The intensification of western boundary currents in the global ocean will potentially influence meso-scale eddy generation, and redistribute microbes and their associated ecological and biogeochemical functions. To understand eddy-induced changes in microbial community composition as well as how they control growth, we targeted the East Australian Current (EAC) region to sample microbes in a cyclonic (cold-core) eddy (CCE) and the adjacent EAC. Phototrophic and diazotrophic microbes were more diverse (2-10 times greater Shannon index) in the CCE relative to the EAC, and the cell size distribution in the CCE was dominated (67%) by larger micro-plankton [Formula: see text], as opposed to pico- and nano-sized cells in the EAC. Nutrient addition experiments determined that nitrogen was the principal nutrient limiting growth in the EAC, while iron was a secondary limiting nutrient in the CCE. Among the diazotrophic community, heterotrophic NifH gene sequences dominated in the EAC and were attributable to members of the gamma-, beta-, and delta-proteobacteria, while the CCE contained both phototrophic and heterotrophic diazotrophs, including Trichodesmium, UCYN-A and gamma-proteobacteria. Daily sampling of incubation bottles following nutrient amendment captured a cascade of effects at the cellular, population and community level, indicating taxon-specific differences in the speed of response of microbes to nutrient supply. Nitrogen addition to the CCE community increased picoeukaryote chlorophyll a quotas within 24 h, suggesting that nutrient uplift by eddies causes a 'greening' effect as well as an increase in phytoplankton biomass. After three days in both the EAC and CCE, diatoms increased in abundance with macronutrient (N, P, Si) and iron amendment, whereas haptophytes and phototrophic dinoflagellates declined. Our results indicate that cyclonic eddies increase delivery of nitrogen to the upper ocean to potentially mitigate the negative consequences of increased stratification due to ocean warming, but also increase the biological demand for iron that is necessary to sustain the growth of large-celled phototrophs and potentially support the diversity of diazotrophs over longer time-scales.
Mokrowiecka, Anna; Veits, Lothar; Falkeis, Christina; Musial, Jacek; Kordek, Radzislaw; Lochowski, Mariusz; Kozak, Jozef; Wierzchniewska-Lawska, Agnieszka; Vieth, Michael; Malecka-Panas, Ewa
2017-03-01
Barrett's esophagus (BE), which develops as a result of gastroesophageal reflux disease, is a preneoplastic condition for esophageal adenocarcinoma (EAC). A new hypothesis suggests that cancer is a disease of stem cells, however, their expression and pathways in BE - EAC sequence are not fully elucidated yet. We used a panel of putative cancer stem cells markers to identify stem cells in consecutive steps of BE-related cancer progression. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded blocks from 58 patients with normal cardiac mucosa (n=5), BE (n=14), early EAC (pT1) from mucosal resection (n=17) and advanced EAC (pT1-T4) from postoperative specimens (n=22). Expression of the CD133, CD44, Musashi-1 and EpCAM was analyzed using respective monoclonal antibodies. All markers showed a heterogeneous expression pattern, mainly at the base of the crypts of Barrett's epithelium and EAC, with positive stromal cells in metaplastic and dysplastic lesions. Immuno-expression of EpCAM, CD44 and CD133 in cardiac mucosa was significantly lower (mean immunoreactivity score (IRS)=1.2; 0.0; 0.4; respectively) compared to their expression in Barrett's metaplasia (mean IRS=4.3; 0.14; 0.7; respectively), in early adenocarcinoma (mean IRS=4.4; 0.29; 1.3; respectively) and in advanced adenocarcinoma (mean IRS=6.6; 0.7; 2.7; respectively) (p<0.05). On the contrary, Musashi-1 expression was higher in BE and early ADC compared to GM and advanced ADC (NS). Our results suggest that the stem cells could be present in premalignant lesions. EpCAM, CD44 and CD133 expression could be candidate markers for BE progression, whereas Musashi-1 may be a marker of the small intestinal features of Barrett's mucosa. Copyright © 2016 Elsevier GmbH. All rights reserved.
Cutaway line drawing of STS-34 middeck experiment Polymer Morphology (PM)
NASA Technical Reports Server (NTRS)
1989-01-01
Cutaway line drawing shows components of STS-34 middeck experiment Polymer Morphology (PM). Components include the EAC, heat exchanger, sample cell control (SCC), sample cells, source, interferometer, electronics, carousel drive, infrared (IR) beam, and carousel. PM, a 3M-developed organic materials processing experiment, is designed to explore the effects of microgravity on polymeric materials as they are processed in space. The samples of polymeric materials being studied in the PM experiment are thin films (25 microns or less) approximately 25mm in diameter. The samples are mounted between two infrared transparent windows in a specially designed infrared cell that provides the capability of thermally processing the samples to 200 degrees Celsius with a high degree of thermal control. The samples are mounted on a carousel that allows them to be positioned, one at a time, in the infrared beam where spectra may be acquired. The Generic Electronics Module (GEM) provides all carousel and
Samuels, Tina; Hoekzema, Craig; Gould, Jon; Goldblatt, Matthew; Frelich, Matthew; Bosler, Matthew; Lee, Sang-Hyuk; Johnston, Nikki
2015-11-01
Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated. Normal and Barrett's biopsies from 8 Barrett's esophagus patients were collected for pepsin analysis via Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1 mg/mL; 1-20 hours), acid (pH 4)±pepsin (5 minutes); real-time RT-PCR, ELISA, and cell migration were assayed. Pepsin was detected in all 8 Barrett's and 4 of 8 adjacent normal specimens. Pepsinogen mRNA was observed in 22 Barrett's, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL-1β expression and cell migration in vitro. Pepsin is synthesized by metaplastic, Barrett's esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in the prevention of EAC. © The Author(s) 2015.
Pathogenesis of Middle Ear Cholesteatoma
Yamamoto-Fukuda, Tomomi; Hishikawa, Yoshitaka; Shibata, Yasuaki; Kobayashi, Toshimitsu; Takahashi, Haruo; Koji, Takehiko
2010-01-01
Middle ear cholesteatoma is characterized by enhanced proliferation of epithelial cells with aberrant morphological characteristics. To investigate the origin of the cholesteatoma cells, we analyzed spontaneously occurring cholesteatomas associated with a new transplantation model in Mongolian gerbils (gerbils). Cholesteatomas were induced in gerbils with a transplanted tympanic membrane by using the external auditory canal (EAC) ligation method. After the pars flaccida of the tympanic membranes were completely removed from male gerbils, corresponding portions of tympanic membranes of female gerbils were transplanted to the area of defect, and then we ligated the EAC (hybrid-model group). As a control group, the EAC of normal male and female gerbils was ligated without myringoplasty. In all ears of each group, the induced cholesteatomas were seen. In situ PCR was then performed to detect the mouse X chromosome-linked phosphoglycerate kinase-1 (pgk-1) gene on the paraffin sections. One pgk-1 spot in the epithelial nuclei was detected in male cholesteatoma, and two pgk-1 spots were detected in female cholesteatoma, respectively. On the other hand, in the hybrid-model group, we detected not only one but also two pgk-1 spots in the epithelial nuclei of cholesteatoma. These results strengthened the evidence that the origin of epithelial cells in cholesteatoma is the tympanic membrane in this model, but not the residential middle ear epithelial cells or the skin of the EAC. PMID:20413684
Yamamoto-Fukuda, Tomomi; Hishikawa, Yoshitaka; Shibata, Yasuaki; Kobayashi, Toshimitsu; Takahashi, Haruo; Koji, Takehiko
2010-06-01
Middle ear cholesteatoma is characterized by enhanced proliferation of epithelial cells with aberrant morphological characteristics. To investigate the origin of the cholesteatoma cells, we analyzed spontaneously occurring cholesteatomas associated with a new transplantation model in Mongolian gerbils (gerbils). Cholesteatomas were induced in gerbils with a transplanted tympanic membrane by using the external auditory canal (EAC) ligation method. After the pars flaccida of the tympanic membranes were completely removed from male gerbils, corresponding portions of tympanic membranes of female gerbils were transplanted to the area of defect, and then we ligated the EAC (hybrid-model group). As a control group, the EAC of normal male and female gerbils was ligated without myringoplasty. In all ears of each group, the induced cholesteatomas were seen. In situ PCR was then performed to detect the mouse X chromosome-linked phosphoglycerate kinase-1 (pgk-1) gene on the paraffin sections. One pgk-1 spot in the epithelial nuclei was detected in male cholesteatoma, and two pgk-1 spots were detected in female cholesteatoma, respectively. On the other hand, in the hybrid-model group, we detected not only one but also two pgk-1 spots in the epithelial nuclei of cholesteatoma. These results strengthened the evidence that the origin of epithelial cells in cholesteatoma is the tympanic membrane in this model, but not the residential middle ear epithelial cells or the skin of the EAC.
Esener, Obb; Balkan, B M; Armutak, E I; Uvez, A; Yildiz, G; Hafizoglu, M; Yilmazer, N; Gurel-Gurevin, E
2018-04-12
Donkey milk and donkey milk kefir exhibit antiproliferative, antimutagenic and antibacterial effects. We investigated the effects of donkey milk and donkey milk kefir on oxidative stress, apoptosis and proliferation in Ehrlich ascites carcinoma (EAC) in mice. Thirty-four adult male Swiss albino mice were divided into four groups as follows: group 1, administered 0.5 ml water; group 2, administered 0.5 ml water + EAC cells; group 3, administered 0.5 ml donkey milk + EAC cells; group 4, administered 0.5 ml donkey milk kefir + EAC cells. We introduced 2.5 x 10 6 EAC cells into each animal by subcutaneous injection. Tap water, donkey milk and donkey milk kefir were administered by gavage for 10 days. Animals were sacrificed on day 11. After measuring the short and long diameters of the tumors, tissues were processed for histology. To determine oxidative stress, cell death and proliferation iNOS and eNOS, active caspase-3 and proliferating cell nuclear antigen were assessed using immunohistochemistry. A TUNEL assay also was used to detect apoptosis. Tumor volume decreased in the donkey milk kefir group compared to the control and donkey milk groups. Tumor volume increased in the donkey milk group compared to the control group. Proliferating cell nuclear antigen levels were higher in the donkey milk kefir group compared to the control and donkey milk groups. The number of apoptotic cells was less in the donkey milk group, compared to the control, whereas it was highest in the donkey milk kefir group. Donkey milk administration increased eNOS levels and decreased iNOS levels, compared to the control group. In the donkey milk kefir group, iNOS levels were significantly lower than those of the control and donkey milk groups, while eNOS levels were similar to the control group. Donkey milk kefir induced apoptosis, suppressed proliferation and decreased co-expression of iNOS and eNOS. Donkey milk promoted development of the tumors. Therefore, donkey milk kefir appears to be more beneficial for treating breast cancer than donkey milk.
Goldman, Aaron; Chen, Hwu Dau Rw; Roesly, Heather B.; Hill, Kimberly A.; Tome, Margaret E.; Dvorak, Bohuslav; Bernstein, Harris
2011-01-01
Barrett's esophagus (BE) is a premalignant condition, where normal squamous epithelium is replaced by intestinal epithelium. BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). However, the BE cell of origin is not clear. We hypothesize that BE tissue originates from esophageal squamous cells, which can differentiate to columnar cells as a result of repeated exposure to gastric acid and bile acids, two components of refluxate implicated in BE pathology. To test this hypothesis, we repeatedly exposed squamous esophageal HET1A cells to 0.2 mM bile acid (BA) cocktail at pH 5.5 and developed an HET1AR-resistant cell line. These cells are able to survive and proliferate after repeated 2-h treatments with BA at pH 5.5. HET1AR cells are resistant to acidification and express markers of columnar differentiation, villin, CDX2, and cytokeratin 8/18. HET1AR cells have increased amounts of reactive oxygen species, concomitant with a decreased level and activity of manganese superoxide dismutase compared with parental cells. Furthermore, HET1AR cells express proteins and activate signaling pathways associated with inflammation, cell survival, and tumorigenesis that are thought to contribute to BE and EAC development. These include STAT3, NF-κB, epidermal growth factor receptor (EGFR), cyclooxygenase-2, interleukin-6, phosphorylated mammalian target of rapamycin (p-mTOR), and Mcl-1. The expression of prosurvival and inflammatory proteins and resistance to cell death could be partially modified by inhibition of STAT3 signaling. In summary, our study shows that long-term exposure of squamous cells to BA at acidic pH causes the cells to display the same characteristics and markers as BE. PMID:21127259
Screening of adulterants in powdered foods and ingredients using line-scan Raman chemical imaging.
USDA-ARS?s Scientific Manuscript database
A newly developed line-scan Raman imaging system using a 785 nm line laser was used to authenticate powdered foods and ingredients. The system was used to collect hyperspectral Raman images in the range of 102–2865 wavenumber from three representative food powders mixed with selected adulterants eac...
Abdel-Rahman, Mohamed A; Abdel-Nabi, Ismail M; El-Naggar, Mohamed S; Abbas, Osama A; Strong, Peter N
2013-05-01
It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich's ascites carcinoma (EAC) cells. Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase (p < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced (p < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione. These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel molecules with potential anticancer activity.
2013-01-01
Background It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich’s ascites carcinoma (EAC) cells. Results Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase (p < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced (p < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione. Conclusions These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel molecules with potential anticancer activity. PMID:23849458
Krause, Lutz; Nones, Katia; Loffler, Kelly A; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J; Watson, David I; Lord, Reginald V; Phillips, Wayne A; Gotley, David; Smithers, B Mark; Whiteman, David C; Hayward, Nicholas K; Grimmond, Sean M; Waddell, Nicola; Barbour, Andrew P
2016-04-01
The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. © The Author 2016. Published by Oxford University Press.
Petrou, Katherina; Sinutok, Sutinee; Seymour, Justin R.; Messer, Lauren F.; Brown, Mark V.; Norman, Louiza; Everett, Jason D.; McInnes, Allison S.; Ralph, Peter J.; Thompson, Peter A.; Hassler, Christel S.
2016-01-01
The intensification of western boundary currents in the global ocean will potentially influence meso-scale eddy generation, and redistribute microbes and their associated ecological and biogeochemical functions. To understand eddy-induced changes in microbial community composition as well as how they control growth, we targeted the East Australian Current (EAC) region to sample microbes in a cyclonic (cold-core) eddy (CCE) and the adjacent EAC. Phototrophic and diazotrophic microbes were more diverse (2–10 times greater Shannon index) in the CCE relative to the EAC, and the cell size distribution in the CCE was dominated (67%) by larger micro-plankton \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$(\\geq 20\\lrm{\\mu }\\mathrm{m})$\\end{document}≥20μm, as opposed to pico- and nano-sized cells in the EAC. Nutrient addition experiments determined that nitrogen was the principal nutrient limiting growth in the EAC, while iron was a secondary limiting nutrient in the CCE. Among the diazotrophic community, heterotrophic NifH gene sequences dominated in the EAC and were attributable to members of the gamma-, beta-, and delta-proteobacteria, while the CCE contained both phototrophic and heterotrophic diazotrophs, including Trichodesmium, UCYN-A and gamma-proteobacteria. Daily sampling of incubation bottles following nutrient amendment captured a cascade of effects at the cellular, population and community level, indicating taxon-specific differences in the speed of response of microbes to nutrient supply. Nitrogen addition to the CCE community increased picoeukaryote chlorophyll a quotas within 24 h, suggesting that nutrient uplift by eddies causes a ‘greening’ effect as well as an increase in phytoplankton biomass. After three days in both the EAC and CCE, diatoms increased in abundance with macronutrient (N, P, Si) and iron amendment, whereas haptophytes and phototrophic dinoflagellates declined. Our results indicate that cyclonic eddies increase delivery of nitrogen to the upper ocean to potentially mitigate the negative consequences of increased stratification due to ocean warming, but also increase the biological demand for iron that is necessary to sustain the growth of large-celled phototrophs and potentially support the diversity of diazotrophs over longer time-scales. PMID:27168982
3D fiber deposited polymeric scaffolds for external auditory canal wall.
Mota, Carlos; Milazzo, Mario; Panetta, Daniele; Trombi, Luisa; Gramigna, Vera; Salvadori, Piero A; Giannotti, Stefano; Bruschini, Luca; Stefanini, Cesare; Moroni, Lorenzo; Berrettini, Stefano; Danti, Serena
2018-05-07
The external auditory canal (EAC) is an osseocartilaginous structure extending from the auricle to the eardrum, which can be affected by congenital, inflammatory, and neoplastic diseases, thus reconstructive materials are needed. Current biomaterial-based approaches for the surgical reconstruction of EAC posterior wall still suffer from resorption (biological) and extrusion (synthetic). In this study, 3D fiber deposited scaffolds based on poly(ethylene oxide terephthalate)/poly(butylene terephthalate) were designed and fabricated to replace the EAC wall. Fiber diameter and scaffold porosity were optimized, leading to 200 ± 33 µm and 55% ± 5%, respectively. The mechanical properties were evaluated, resulting in a Young's modulus of 25.1 ± 7.0 MPa. Finally, the EAC scaffolds were tested in vitro with osteo-differentiated human mesenchymal stromal cells (hMSCs) with different seeding methods to produce homogeneously colonized replacements of interest for otologic surgery. This study demonstrated the fabrication feasibility of EAC wall scaffolds aimed to match several important requirements for biomaterial application to the ear under the Tissue Engineering paradigm, including shape, porosity, surface area, mechanical properties and favorable in vitro interaction with osteoinduced hMSCs. This study demonstrated the fabrication feasibility of outer ear canal wall scaffolds via additive manufacturing. Aimed to match several important requirements for biomaterial application to ear replacements under the Tissue Engineering paradigm, including shape, porosity and pore size, surface area, mechanical properties and favorable in vitro interaction with osteo-differentiated mesenchymal stromal cells.
Immobilization of glucose oxidase into polyaniline nanofiber matrix for biofuel cell applications.
Kim, Hyeongseok; Lee, Inseon; Kwon, Yongchai; Kim, Byoung Chan; Ha, Su; Lee, Jung-heon; Kim, Jungbae
2011-05-15
Glucose oxidase (GOx) was immobilized into the porous matrix of polyaniline nanofibers in a three-step process, consisting of enzyme adsorption, precipitation, and crosslinking (EAPC). EAPC was highly active and stable when compared to the control samples of enzyme adsorption (EA) and enzyme adsorption and crosslinking (EAC) with no step of enzyme precipitation. The GOx activity of EAPC was 9.6 and 4.2 times higher than those of EA and EAC, respectively. Under rigorous shaking at room temperature for 56 days, the relative activities of EA, EAC and EAPC, defined as the percentage of residual activity to the initial activity, were 22%, 19% and 91%, respectively. When incubated at 50°C under shaking for 4h, EAPC showed a negligible decrease of GOx activity while the relative activities of EA and EAC were 45% and 48%, respectively. To demonstrate the feasible application of EAPC in biofuel cells, the enzyme anodes were prepared and used for home-built air-breathing biofuel cells. The maximum power densities of biofuel cells with EA and EAPC anodes were 57 and 292 μW/cm(2), respectively. After thermal treatment at 60°C for 4h, the maximum power density of EA and EAPC anodes were 32 and 315 μW/cm(2), representing 56% and 108% of initially obtained maximum power densities, respectively. Because the lower power densities and short lifetime of biofuel cells are serious problems against their practical applications, the present results with EAPC anode has opened up a new potential for the realization of practical biofuel cell applications. Copyright © 2011 Elsevier B.V. All rights reserved.
Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds.
Pain, Anindita; Samanta, Suva; Dutta, Sushanta; Saxena, Ajit K; Shanmugavel, Mutiah; Sharma, Madhunika; Qazi, Gulam N; Sanyal, Utpal
2007-01-01
Four new ethylnitrosourea derivatives of substituted naphthalimides 3a-d have been synthesized from the respective N-(2-ethylamino) naphthalimides. Their chemical alkylating activity compared with the clinical drug CCNU and an experimental compound Mitonafide indicated that they possess lower alkylating activity than CCNU and comparable activity with the latter. Their anti-tumor efficacies were assessed in vivo in two murine ascites tumors namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. CCNU and Mitonafide were used as positive controls for comparison. The representative compound 3a has displayed marginal anti-tumoral activity in these tumors. Three compounds were further screened in vitro in 4 different human tumor cell lines but no significant activity was observed in those lines. These compounds moderately inhibit the synthesis of DNA and RNA in S-180 tumor cells.
Anti-cancer activity of bromelain nanoparticles by oral administration.
Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C
2014-12-01
Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy.
Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds
DOE Office of Scientific and Technical Information (OSTI.GOV)
Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.
2009-04-01
Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused bymore » these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects.« less
Gall, Alevtina; Fero, Jutta; McCoy, Connor; Claywell, Brian C.; Sanchez, Carissa A.; Blount, Patricia L.; Li, Xiaohong; Vaughan, Thomas L.; Matsen, Frederick A.; Reid, Brian J.; Salama, Nina R.
2015-01-01
Background The incidence of esophageal adenocarcinoma (EAC) has increased nearly five-fold over the last four decades in the United States. Barrett’s esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear. Methodology The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12) of the Seattle Barrett’s Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett’s esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this cohort. Results/Significance Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett’s esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett’s esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC. PMID:26076489
NASA Astrophysics Data System (ADS)
Saif, M.; El-Shafiy, Hoda F.; Mashaly, Mahmoud M.; Eid, Mohamed F.; Nabeel, A. I.; Fouad, R.
2018-06-01
Three novel Eu(III) phosphor complexes, [Eu(HL)(OH2)2(C2H5OH)](NO3)2 (1), [Eu(HL)(Bpy)(NO3)2(EtOH)] (2) and [Eu(HL)(Phen)(NO3)2(H2O)] (3) (HL = (11E)-2-hydroxy-N/-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide; Bpy = 2,2/-bibyridyl and Phen = 1,10-phenanthroline) were prepared. Elemental, thermal, FT-IR and XRD methods were used to characterize their structural configuration. The HL behaves as a monoanionic tridentate ligand. The XRD analysis shows that the ligand and its Eu3+complexes are in nano domain. From fluorescence spectroscopy, all the prepared complexes are highly luminescent, having an impressive visual emission under UV excitation. The H2L and its Eu3+nano-complexes (1-3) were tested for their in vitro cytotoxicity against Ehrlich Ascites Carcinoma cell line (EAC). The Eu(III) nano-complexes (1-3) effectively inhibited EAC growth with IC50 value of 25 μM. The high antitumor activity of the Eu(III) nano-complexes (1-3) were attributed to its chemical structure, and nano size properties.
Habib, Muhammad R; Karim, Muhammad R
2013-01-01
Over 60% of currently used anti-cancer agents are derived in one-way or another from natural sources, including plants, marine organisms and microorganisms. Calotropis gigantea (Linn.) (Family: Asclepiadaceae) is a perennial shrub and it is used as a traditional folk medicine for the treatment of various health complications. But there is no report on isolation of anticancerous chemicals from the flower of Calotropis gigantea. The objective of the present study is to explore the antitumor effect of anhydrosophoradiol-3-acetate (A3A), isolated from the flower of Calotropis gigantea (Linn.) against Ehrlich's ascites carcinoma (EAC) in Swiss albino mice. Antitumoric effect of A3A was assessed by evaluating viable tumor cell count, survival time, body weight gain due to tumor burden, hematological and biochemical (glucose, cholesterol, triglyceride, blood urea, SALP, SGPT and SGOT) parameters of EAC bearing host at doses of 10 and 20 mg/kg body weight. Treatment with A3A decreased the viable tumor cells and body weight gain thereby increasing the life span of EAC bearing mice. A3A also brought back the altered hematological (Hb, total RBC and total WBC) and biochemical parameters more or less to normal level. Results of this study conclude that in vivo the A3A was effective in inhibiting the growth of EAC with improving in cancer induced complications.
Adamovic, Tatjana; Hamta, Ahmad; Roshani, Leyla; Lü, Xuchun; Röhme, Dan; Helou, Khalil; Klinga-Levan, Karin; Levan, Göran
2008-07-01
The inbred BDII rat is a valuable experimental model for the genetic analysis of hormone-dependent endometrial adenocarcinoma (EAC). One common aberration detected previously by comparative genomic hybridization in rat EAC is loss affecting mostly the middle part of rat chromosome 5 (RNO5). First, we applied an RNO5-specific painting probe and four region-specific gene probes onto tumor cell metaphases from 21 EACs, and found that rearrangements involving RNO5 were common. The copy numbers of loci situated on RNO5 were found to be reduced, particularly for the CDKN2A/2B locus. Second, polymerase chain reaction analysis was performed with 22 genes and markers and homozygous deletions of the CDKN2A exon 1beta and CDKN2B genes were detected in 13 EACs (62%) and of CDKN2A exon 1alpha in 12 EACs (57%) Third, the occurrence of allelic imbalance in RNO5 was analyzed using 39 microsatellite markers covering the entire chromosome and frequent loss of heterozygosity was detected. Even more intriguing was the repeated finding of allele switching in a narrow region of 7 Mb across the CDKN2A/2B locus. We conclude that genetic events affecting the middle part of RNO5 (including bands 5q31 approximately q33 and the CDKN2A locus) contribute to the development of EAC in rat, with the CDKN2A locus having a primary role.
Single nucleotide polymorphisms in obesity-related genes and the risk of esophageal cancers.
Doecke, James D; Zhao, Zhen Zhen; Stark, Mitchell S; Green, Adèle C; Hayward, Nicholas K; Montgomery, Grant W; Webb, Penelope M; Whiteman, David C
2008-04-01
Rates of adenocarcinoma of the esophagus (EAC) and esophagogastric junction (EGJAC) have been rising rapidly in recent decades, in contrast to the declining rates of esophageal squamous cell carcinomas (ESCC). Obesity is a major risk factor for both EAC and EGJAC, but not ESCC, and there is speculation that obesity promotes adenocarcinoma development through endocrine and related pathways. We therefore compared the prevalence of 12 single nucleotide polymorphisms (SNPs) in nine candidate genes previously implicated in obesity pathways (LEP, LEPR, ADIPOQ, POMC, PPARalpha, PPARgamma, RXRgamma, GHRL, and INSIG2) in a large Australian case-control study comprising DNA samples from 260 EAC cases, 301 EGJAC cases, 213 ESCC cases, and 1,352 population controls. No SNPs were associated with EGJAC or ESCC. Although several SNPs seemed to be associated with EAC on crude analysis [ADIPOQ (rs1501299), LEP (5'-untranslated region), PPARgamma (H447H), and GHRL (M72L)], effect sizes were modest and none of the associations was significant after correcting for multiple comparisons. Further, we found no consistent evidence that any of the genotypes were associated with risk of EAC or EGJAC within strata of body mass index (<25.0 kg/m(2), 25.0-29.9 kg/m(2), >30 kg/m(2)). In conclusion, our data suggest that these SNPs do not play a major role in esophageal carcinogenesis.
Heberle, Curtis R; Omidvari, Amir-Houshang; Ali, Ayman; Kroep, Sonja; Kong, Chung Yin; Inadomi, John M; Rubenstein, Joel H; Tramontano, Angela C; Dowling, Emily C; Hazelton, William D; Luebeck, E Georg; Lansdorp-Vogelaar, Iris; Hur, Chin
2017-09-01
It is important to identify patients with Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma (EAC). Patients with BE usually are identified by endoscopy, which is expensive. The Cytosponge, which collects tissue from the esophagus noninvasively, could be a cost-effective tool for screening individuals with gastroesophageal reflux disease (GERD) who are at increased risk for BE. We developed a model to analyze the cost effectiveness of using the Cytosponge in first-line screening of patients with GERD for BE with endoscopic confirmation, compared with endoscopy screening only. We incorporated data from a large clinical trial of Cytosponge performance into 2 validated microsimulation models of EAC progression (the esophageal adenocarcinoma model from Massachusetts General Hospital and the microsimulation screening analysis model from Erasmus University Medical Center). The models were calibrated for US Surveillance, Epidemiology and End Results data on EAC incidence and mortality. In each model, we simulated the effect of a 1-time screen for BE in male patients with GERD, 60 years of age, using endoscopy alone or Cytosponge collection of tissue, and analysis for the level of trefoil factor 3 with endoscopic confirmation of positive results. For each strategy we recorded the number of cases of EAC that developed, the number of EAC cases detected with screening by Cytosponge only or by subsequent targeted surveillance, and the number of endoscopies needed. In addition, we recorded the cumulative costs (including indirect costs) incurred and quality-adjusted years of life lived within each strategy, discounted at a rate of 3% per year, and computed incremental cost-effectiveness ratios (ICERs) among the 3 strategies. According to the models, screening patients with GERD by Cytosponge with follow-up confirmation of positive results by endoscopy would reduce the cost of screening by 27% to 29% compared with screening by endoscopy, but led to 1.8 to 5.5 (per 1000 patients) fewer quality-adjusted life years. The ICERs for Cytosponge screening compared with no screening ranged from $26,358 to $33,307. For screening patients by endoscopy compared with Cytosponge the ICERs ranged from $107,583 to $330,361. These results were sensitive to Cytosponge cost within a plausible range of values. In a comparative modeling analysis of screening strategies for BE in patients with GERD, we found Cytosponge screening with endoscopic confirmation to be a cost-effective strategy. The greatest benefit was achieved by endoscopic screening, but with an unfavorable cost margin. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Suthers, Iain M.; Young, Jock W.; Baird, Mark E.; Roughan, Moninya; Everett, Jason D.; Brassington, Gary B.; Byrne, Maria; Condie, Scott A.; Hartog, Jason R.; Hassler, Christel S.; Hobday, Alistair J.; Holbrook, Neil J.; Malcolm, Hamish A.; Oke, Peter R.; Thompson, Peter A.; Ridgway, Ken
2011-03-01
The poleward flowing East Australian Current (EAC) is characterised by its separation from the coast, 100-200 nautical miles north of Sydney, to form the eastward flowing Tasman Front and a southward flowing eddy field. The separation zone greatly influences coastal ecosystems for the relatively narrow continental shelf (only 15-50 km wide), particularly between 32-34°S. In this region the continental shelf has a marked shift in the seasonal temperature-salinity relationship and elevated surface nitrate concentrations. This current parallels the portion of the coast where Australia's population is concentrated and has a long history of scientific research. However, understanding of physical and biological processes driven by the EAC, particularly in linking circulation to ecosystems, is limited. In this special issue of 16 papers on the EAC, we examine the effects of climatic wind-stress forced ocean dynamics on EAC transport variability and coastal sea level, from ENSO to multi-decadal time scales; eddy formation and structure; fine scale connectivity and larval retention. Comparisons with the poleward-flowing Leeuwin Current on Australia's west coast show differences in ecosystem productivity that can be attributed to the underlying physics in each region. On average there is double the chlorophyll a concentration on the east coast than the west. In comparison to the Leeuwin, the EAC may have less local retention of larvae and act as a partial barrier to onshore transport, which may also be related to the local spawning and early life history of small pelagic fish on each coast. Inter-annual variations in the EAC transport produce a detectable sea-level signal in Sydney Harbour, which could provide a useful fisheries index as does the Fremantle sea level and Leeuwin Current relationship. The EAC's eddy structure and formation by the EAC are examined. A particular cold-core eddy is shown to have a "tilt" towards the coast, and that during a rotation the flow of particles may rise up to the euphotic zone and then down beneath. In a warm-core eddy, surface flooding is shown to produce a new shallower surface mixed layer and promote algal growth. An assessment of plankton data from 1938-1942 showed that the local, synoptic conditions had to be incorporated before any comparison with the present. There are useful relationships of water mass characteristics in the Tasman Sea and separation zone with larval fish diversity and abundance, as well as with long-line fisheries. These fisheries-pelagic habitat relationships are invaluable for fisheries management, as well as for climate change assessments. There is further need to examine the EAC influence on rainfall, storm activity, dust deposition, and on the movements by fish, sharks and whales. The Australian Integrated Marine Observing System (IMOS) has provided new infrastructure to determine the changing behaviour of the EAC and its bio-physical interaction with the coasts and estuaries. The forecasting and hindcasting capability developed under the Bluelink project has provided a new tool for data synthesis and dynamical analysis. The impact of a strengthening EAC and how it influences the livelihoods of over half the Australian population, from Brisbane to Sydney, Hobart and Melbourne, is just being realised.
75 FR 17912 - Sunshine Act; Notice of Virtual Public Forum for EAC Board of Advisors
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-08
... ELECTION ASSISTANCE COMMISSION Sunshine Act; Notice of Virtual Public Forum for EAC Board of...: EAC Board of Advisors Virtual Meeting Room at http://www.eac.gov . Once at the main page of EAC's Web site, viewers should click the link to the Board of Advisors Virtual Meeting Room. The virtual meeting...
Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia
Zhou, Juan; He, Lei; Pang, Zhijun; Appelman, Henry D.; Kuick, Rork; Beer, David G.; Li, Meng; Wang, Thomas D.
2017-01-01
The incidence of esophageal adenocarcinoma (EAC) is rising rapidly, and early detection within the precursor state of Barrett's esophagus (BE) is challenged by flat premalignant lesions that are difficult detect with conventional endoscopic surveillance. Overexpression of cell surface fibroblast growth factor receptor 2 (FGFR2) is an early event in progression of BE to EAC, and is a promising imaging target. We used phage display to identify the peptide SRRPASFRTARE that binds specifically to the extracellular domain of FGFR2. We labeled this peptide with a near-infrared fluorophore Cy5.5, and validated the specific binding to FGFR2 overexpressed in cells in vitro. We found high affinity kd = 68 nM and rapid binding k = 0.16 min−1 (6.2 min). In human esophageal specimens, we found significantly greater peptide binding to high-grade dysplasia (HGD) versus either BE or normal squamous epithelium, and good correlation with anti-FGFR2 antibody. We also observed significantly greater peptide binding to excised specimens of esophageal squamous cell carcinoma and gastric cancer compared to normal mucosa. These results demonstrate potential for this FGFR2 peptide to be used as a clinical imaging agent to guide tissue biopsy and improve methods for early detection of EAC and potentially other epithelial-derived cancers. PMID:29152066
Autologous engineering of cartilage
Emans, Pieter J.; van Rhijn, Lodewijk W.; Welting, Tim J. M.; Cremers, Andy; Wijnands, Nina; Spaapen, Frank; Voncken, J. Willem; Shastri, V. Prasad
2010-01-01
Treatment of full-thickness damage to hyaline cartilage is hampered by the limited availability of autologous healthy cartilage and the lengthy, cost-prohibitive cell isolation and expansion steps associated with autologous cartilage implantation (ACI). Here we report a strategy for de novo engineering of ectopic autologous cartilage (EAC) within the subperiosteal space (in vivo bioreactor), through the mere introduction of a biocompatible gel that might promote hypoxia-mediated chondrogenesis, thereby effectively overcoming the aforementioned limitations. The EAC is obtained within 3 wk post injection of the gel, and can be press-fit into an osteochondral defect where it undergoes remodeling with good lateral and subchondral integration. The implanted EAC showed no calcification even after 9 mo and attained an average O’Driscoll score of 11 (versus 4 for controls). An “on demand” autologous source of autologous cartilage with remodeling capacity is expected to significantly impact the clinical options in repair of trauma to articular cartilage. PMID:20133690
The incidence of esophageal adenocarcinoma (EAC) has risen five-fold over the past several decades, yet the prognosis for EAC remains extremely poor. As such, EAC represents a very attractive target for chemoprevention. Barrett's esophagus (BE) is the precursor lesion for EAC, and acid reflux is a major risk factor for both BE and EAC. Virtually all patients with BE,
Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis
Patch, Ann-Marie; Bailey, Peter; Newell, Felicity; Holmes, Oliver; Fink, J. Lynn; Quinn, Michael C.J.; Tang, Yue Hang; Lampe, Guy; Quek, Kelly; Loffler, Kelly A.; Manning, Suzanne; Idrisoglu, Senel; Miller, David; Xu, Qinying; Waddell, Nick; Wilson, Peter J.; Bruxner, Timothy J.C.; Christ, Angelika N.; Harliwong, Ivon; Nourse, Craig; Nourbakhsh, Ehsan; Anderson, Matthew; Kazakoff, Stephen; Leonard, Conrad; Wood, Scott; Simpson, Peter T.; Reid, Lynne E.; Krause, Lutz; Hussey, Damian J.; Watson, David I.; Lord, Reginald V.; Nancarrow, Derek; Phillips, Wayne A.; Gotley, David; Smithers, B. Mark; Whiteman, David C.; Hayward, Nicholas K.; Campbell, Peter J.; Pearson, John V.; Grimmond, Sean M.; Barbour, Andrew P.
2015-01-01
Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n = 40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. PMID:25351503
Treviño-Garza, Mayra Z; García, Santos; del Socorro Flores-González, Ma; Arévalo-Niño, Katiushka
2015-08-01
Edible active coatings (EACs) based on pectin, pullulan, and chitosan incorporated with sodium benzoate and potassium sorbate were employed to improve the quality and shelf life of strawberries. Fruits were washed, disinfected, coated by dipping, packed, and stored at 4 °C for 15 d. Application of EACs reduced (P < 0.05) weight loss and fruit softening and delayed alteration of color (redness) and total soluble solids content. In contrast, pH and titratable acidity were not affected (P > 0.05) throughout storage, and ascorbic acid content was maintained in pectin-EAC coated strawberries. Microbiological analyses showed that application of EACs reduced (P < 0.05) microbial growth (total aerobic counts, molds, and yeasts) on strawberries. Chitosan-EAC coated strawberries presented the best results in microbial growth assays. Sensory quality (color, flavor, texture, and acceptance) improved and decay rate decreased (P < 0.05) in pectin-EAC, pullulan-EAC, and chitosan-EAC coated strawberries. In conclusion, EACs based on polysaccharides improved the physicochemical, microbiological, and sensory characteristics, increasing the shelf life of strawberries from 6 (control) to 15 d (coated fruits). © 2015 Institute of Food Technologists®
BINDING OF SOLUBLE IMMUNE COMPLEXES TO HUMAN LYMPHOBLASTOID CELLS
Theofilopoulos, Argyrios N.; Dixon, Frank J.; Bokisch, Viktor A.
1974-01-01
In the present work we studied the expression of membrane-bound Ig (MBIg) as well as receptors for IgG Fc and complement on nine human lymphoblastoid cell lines. When MBIg and receptors for IgG Fc were compared, four categories of cell lines could be distinguished: (a) cell lines having both MBIg and receptors for IgG Fc, (b) cell lines having MBIg but lacking receptors for IgG Fc, (c) cell lines lacking MBIg but having receptors for IgG Fc, and (d) cell lines lacking both MBIg and receptors for IgG Fc. Two types of receptors for complement could be detected on the cell lines studied, one for C3-C3b and one for C3d. When sensitized red cells carrying C3b or C3d were used for rosette tests, three categories of cell lines could be distinguished: (a) cell lines having receptors for C3b and C3d, (b) cell lines having receptors only for C3d and (c) cell lines lacking both receptors. However, when a more sensitive immunofluorescent method was used instead of the rosette technique, it was found that cell lines unable to form rosettes with EAC1423bhu were able to bind soluble C3 or C3b which indicated the presence of these receptors on the cell surface. Inhibition experiments showed that receptors for C3-C3b and receptors for C3d are distinct and that receptors for C3-C3b and C3d are different from receptors for IgG Fc. A cell line (Raji) without MBIg but with receptors for IgG Fc, C3-C3b, and C3d was selected for use in studying the binding mechanism of soluble immune complexes to cell surface membrane. Aggregated human gamma globulin was used in place of immune complexes. Immune complexes containing complement bind to Raji cells only via receptors for complement, namely receptors for C3-C3b and C3d. Binding of immune complexes containing complement to cells is much greater than that of complexes without complement. Immune complexes bound to cells via receptors for complement can be partially released from the cell surface by addition of normal human serum as well as isolated human C3 or C3b. We postulate that such release is due to competition of immune complex bound C3b and free C3 or C3b for the receptors on Raji cells. PMID:4139225
75 FR 17913 - Sunshine Act; Notice of Virtual Public Forum for EAC Standards Board
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-08
... ELECTION ASSISTANCE COMMISSION Sunshine Act; Notice of Virtual Public Forum for EAC Standards... Standards Board Virtual Meeting Room at http://www.eac.gov . Once at the main page of EAC's Web site, viewers should click the link to the Standards Board Virtual Meeting Room. The virtual meeting room will...
76 FR 27641 - Sunshine Act Notice
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-12
.... ACTION: Notice of Virtual Public Forum for EAC Standards Board. DATE AND TIME: Tuesday, May 31, 2011, 10 a.m. EDT through Tuesday, June 14, 2011, 10 a.m. EDT. PLACE: EAC Standards Board Virtual Public Forum at http://www.eac.gov/virtual_public_forum.aspx . Once at the main page of EAC's Web site, viewers...
Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma
Alexandre, Leo; Long, Elizabeth; Beales, Ian LP
2014-01-01
In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett’s esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett’s-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett’s cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits. PMID:25400997
Association between ambient ultraviolet radiation and risk of esophageal cancer.
Tran, Bich; Lucas, Robyn; Kimlin, Michael; Whiteman, David; Neale, Rachel
2012-12-01
Ecological studies have suggested an inverse relationship between latitude and risks of some cancers. However, associations between solar ultraviolet radiation (UVR) exposure and esophageal cancer risk have not been fully explored. We therefore investigated the association between nevi, freckles, and measures of ambient UVR over the life-course with risks of esophageal cancers. We compared estimated lifetime residential ambient UVR among Australian patients with esophageal cancer (330 esophageal adenocarcinoma (EAC), 386 esophago-gastric junction adenocarcinoma (EGJAC), and 279 esophageal squamous cell carcinoma (ESCC)), and 1471 population controls. We asked people where they had lived at different periods of their life, and assigned ambient UVR to each location based on measurements from NASA's Total Ozone Mapping Spectrometer database. Freckling and nevus burden were self-reported. We used multivariable logistic regression models to estimate the magnitude of associations between phenotype, ambient UVR, and esophageal cancer risk. Compared with population controls, patients with EAC and EGJAC were less likely to have high levels of estimated cumulative lifetime ambient UVR (EAC odds ratio (OR) 0.59, 95% confidence interval (CI) 0.35-0.99, EGJAC OR 0.55, 0.34-0.90). We found no association between UVR and risk of ESCC (OR 0.91, 0.51-1.64). The associations were independent of age, sex, body mass index, education, state of recruitment, frequency of reflux, smoking status, alcohol consumption, and H. pylori serostatus. Cases with EAC were also significantly less likely to report high levels of nevi than controls. These data show an inverse association between ambient solar UVR at residential locations and risk of EAC and EGJAC, but not ESCC.
Juth, Vanessa; Dickerson, Sally S; Zoccola, Peggy M; Lam, Suman
2015-01-01
Dispositional emotional approach coping (EAC) marks an adaptive tendency to process and express emotions. EAC's association with cognitions, affect, and intra- and interindividual characteristics that may account for its utility was examined in response to an acute stressor and in daily life. This study included a laboratory stress task and ecological momentary assessment. Healthy undergraduate students (n = 124; mean age: 20; women: 56%) completed a laboratory component (baseline survey, speech stress task, pre- and posttask measures) and five subsequent days of surveys via palm pilot (six surveys/day). Controlling for sex, neuroticism, and social support, greater EAC was associated with more positive cognitive appraisals, personal resources, and positive affect and less-negative affect during the lab stressor, and with more perceived control and positive affect in daily life. Significant EAC × sex interactions were found for poststressor affect: men with high EAC reported more positive affect and women with high EAC reported less negative affect. Findings provide support that EAC's utility may be independent of intra- and interindividual characteristics, and that men and women may benefit from EAC in different ways in regards to affect. The proclivity to use EAC may come with a resiliency that protects against stress and promotes general well-being.
Differential role of microRNAs in the pathogenesis and treatment of Esophageal cancer.
Hemmatzadeh, Maryam; Mohammadi, Hamed; Karimi, Mohammad; Musavishenas, Mohammad Hossein; Baradaran, Behzad
2016-08-01
Esophageal cancer (EC) is the most invasive disease associated with inclusive poor prognosis. EC usually is found as either adenocarcinoma (EAC) or squamous cell carcinomas (ESCC). ESCC forms in squamous cells and highly occurs in the upper third of the esophagus. EAC appears in glandular cells and ordinarily develops in the lower one third of the esophagus near the stomach. Barrett's esophagus (BE) is a metaplastic precursor of EAC. There is a persistent need for improving our understanding of the molecular basis of this disease. MicroRNAs (miRNAs) demonstrate an uncovered class of small, non-coding RNAs that can negatively regulate the protein coding gene, and are associated with approximately all known physiological and pathological processes, especially cancer. MiRNAs can affect cancer pathogenesis, playing a crucial role as either oncogenes or tumor suppressors. The recent emergence of observations on the role of miRNAs in cancer and their functions has induced many investigations to examine their relevance to esophageal cancer. In esophageal cancer, miRNA dysregulation plays a crucial role in cancer prognosis and in patients' responsiveness to neo-adjuvant and adjuvant therapies. In this review, the oncogenic, tumor suppressive, and drug resistance related roles of miRNAs, and their involvement in the pathogenesis and treatment of esophageal cancer were summarized. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Endometrioid Adenocarcinoma Arising in a Paratubal Cyst: A Case Report and Review of the Literature.
Chang, Catherine; Matsuo, Koji; Mhawech-Fauceglia, Paulette
2017-03-01
A 56-year-old G3P3 postmenopausal woman presented with a 5 month history of abnormal uterine bleeding and pelvic pain. A computed tomographic scan revealed a 5 cm right adnexal cystic mass in addition to a thickened, heterogenous endometrium and leiomyomatous uterus. A total laparascopic hysterectomy and bilateral salpingo-oophorectomy with omental and peritoneal biopsy were performed. Gross examination revealed a 12 week size uterus with small fibroids, normal bilateral atrophic ovaries, and a right paratubal cyst. A 4 cm vegetating mass was found in the right side of the uterine wall. Microscopically, the uterine mass was diagnosed as an endometrioid adenocarcinoma (EAC) FIGO 1 with 70% of myometrial invasion. The remaining endometrium showed a complex atypical hyperplasia. In addition, a 5 cm paratubal cystic mass was found that was separate from the uterus and the right adnexa. The cyst content was a chocolate brown fluid and the cyst wall was smooth with a single solid mass of 2 cm in size. The diagnosis of EAC, FIGO 1 was given. The remaining cyst lining showed endometriotic cyst and foci of endometriosis in the cyst wall. There was no lymphovascular invasion. The entire fallopian tube and ovaries were submitted and they were free of tumor. The patient was diagnosed with primary EAC of the paratubal cyst in addition to EAC of the uterine corpus (pT1b). A close follow-up was recommended. Because of our limited knowledge of carcinomas arising in the paratubal cyst, we will review the literature and discuss their clinical aspects, management, and behavior.
Bhatnagar, Priyanka; Kumari, Manisha; Pahuja, Richa; Pant, A B; Shukla, Y; Kumar, Pradeep; Gupta, K C
2018-06-01
To promote the specific targeting and elimination of CD44-positive cancer cells, berberine chloride (BRB)-encapsulated hyaluronic acid-grafted poly(lactic-co-glycolic acid) copolymer (BRB-d(HA)-g-PLGA) nanoparticles (NPs) were prepared. The targeted action of these NPs was compared to non-targeted BRB-loaded PLGA NPs and bulk BRB. The in vitro studies demonstrated faster release of BRB and increased cytotoxicity of BRB-d(HA)-g-PLGA NPs in Hela and MCF-7 cells in comparison to BRB-PLGA NPs and bulk BRB. The uptake of BRB-d(HA)-g-PLGA NPs was increased in case of MCF-7 cells as compared to HeLa cells owing to the higher expression of CD44 receptors on MCF-7 cells. The CD44 receptor-mediated uptake of these NPs was confirmed through competitive inhibition experiments. The in vitro results were further validated in vivo in Ehrlich Ascites Carcinoma (EAC)-bearing mice. EAC-bearing mice were injected intravenously with these NPs and the results obtained were compared with that of BRB-PLGA NPs and bulk BRB. BRB-d(HA)-g-PLGA NPs were found to significantly enhance apoptosis, sub-G1 content, life span, mean survival time, and ROS levels in EAC cells with subsequent decrease in mitochondrial membrane potential and tumor burden ion tumor-bearing mice. Taking into account the findings of in vitro and in vivo studies, the enhanced and targeted anti-tumor activity of HA-grafted PLGA copolymer-encapsulated NPs of BRB cannot be negated. Therefore, HA-grafted nanoparticle-based delivery of BRB may offer a promising and improved alternative for anti-tumor therapy.
NASA Astrophysics Data System (ADS)
Kang, Yang; Wu, Qiang; Jin, Rui; Yu, Pengfei; Cheng, Jixiang
2016-01-01
This paper reports the facile preparation, mechanical performance and linear viscoelasticity of polyetheramine-cured rubber-like epoxy asphalt composites (EACs) with different asphalt contents. Compared with previous EACs prepared via complex chemical reactions and time-consuming high-temperature curing, the EACs reported here were obtained by using a compatible, bi-functional polyetheramine and a simple physical co-blend process, which make the EACs feasibly scalable for production at a lower cost. The EACs were cured for 1 h at 160 °C and 3 d at 60 °C therefore, these composites can be opened to traffic immediately. The EACs have a much greater temperature stability than common thermoplastic polymer-modified asphalt composites from -30 °C to 120 °C, but their complex shear moduli at higher temperatures slightly decrease instead of remaining constant when temperatures are greater than 80 °C, especially for the higher asphalt content composites; that is, these composites are quasi-thermosetting. Wicket plots illustrate that the EACs reported here are thermorheological simple materials, and the master curves are constructed and well-fitted by generalized logistic sigmoidal model functions. This research provides a facile, low-cost method for the preparation of polyetheramine-cured EACs that can be opened to traffic immediately, and the concept of quasi-thermosetting may facilitate the development of cheaper EACs for advanced applications.
Kang, Yang; Wu, Qiang; Jin, Rui; Yu, Pengfei; Cheng, Jixiang
2016-01-06
This paper reports the facile preparation, mechanical performance and linear viscoelasticity of polyetheramine-cured rubber-like epoxy asphalt composites (EACs) with different asphalt contents. Compared with previous EACs prepared via complex chemical reactions and time-consuming high-temperature curing, the EACs reported here were obtained by using a compatible, bi-functional polyetheramine and a simple physical co-blend process, which make the EACs feasibly scalable for production at a lower cost. The EACs were cured for 1 h at 160 °C and 3 d at 60 °C; therefore, these composites can be opened to traffic immediately. The EACs have a much greater temperature stability than common thermoplastic polymer-modified asphalt composites from -30 °C to 120 °C, but their complex shear moduli at higher temperatures slightly decrease instead of remaining constant when temperatures are greater than 80 °C, especially for the higher asphalt content composites; that is, these composites are quasi-thermosetting. Wicket plots illustrate that the EACs reported here are thermorheological simple materials, and the master curves are constructed and well-fitted by generalized logistic sigmoidal model functions. This research provides a facile, low-cost method for the preparation of polyetheramine-cured EACs that can be opened to traffic immediately, and the concept of quasi-thermosetting may facilitate the development of cheaper EACs for advanced applications.
Kang, Yang; Wu, Qiang; Jin, Rui; Yu, Pengfei; Cheng, Jixiang
2016-01-01
This paper reports the facile preparation, mechanical performance and linear viscoelasticity of polyetheramine-cured rubber-like epoxy asphalt composites (EACs) with different asphalt contents. Compared with previous EACs prepared via complex chemical reactions and time-consuming high-temperature curing, the EACs reported here were obtained by using a compatible, bi-functional polyetheramine and a simple physical co-blend process, which make the EACs feasibly scalable for production at a lower cost. The EACs were cured for 1 h at 160 °C and 3 d at 60 °C; therefore, these composites can be opened to traffic immediately. The EACs have a much greater temperature stability than common thermoplastic polymer-modified asphalt composites from −30 °C to 120 °C, but their complex shear moduli at higher temperatures slightly decrease instead of remaining constant when temperatures are greater than 80 °C, especially for the higher asphalt content composites; that is, these composites are quasi-thermosetting. Wicket plots illustrate that the EACs reported here are thermorheological simple materials, and the master curves are constructed and well-fitted by generalized logistic sigmoidal model functions. This research provides a facile, low-cost method for the preparation of polyetheramine-cured EACs that can be opened to traffic immediately, and the concept of quasi-thermosetting may facilitate the development of cheaper EACs for advanced applications. PMID:26733315
NASA Astrophysics Data System (ADS)
Bull, Christopher Y. S.; Kiss, Andrew E.; Jourdain, Nicolas C.; England, Matthew H.; van Sebille, Erik
2017-12-01
The East Australian Current (EAC), like many other subtropical western boundary currents, is believed to be penetrating further poleward in recent decades. Previous observational and model studies have used steady state dynamics to relate changes in the westerly winds to changes in the separation behavior of the EAC. As yet, little work has been undertaken on the impact of forcing variability on the EAC and Tasman Sea circulation. Here using an eddy-permitting regional ocean model, we present a suite of simulations forced by the same time-mean fields, but with different atmospheric and remote ocean variability. These eddy-permitting results demonstrate the nonlinear response of the EAC to variable, nonstationary inhomogeneous forcing. These simulations show an EAC with high intrinsic variability and stochastic eddy shedding. We show that wind stress variability on time scales shorter than 56 days leads to increases in eddy shedding rates and southward eddy propagation, producing an increased transport and southward reach of the mean EAC extension. We adopt an energetics framework that shows the EAC extension changes to be coincident with an increase in offshore, upstream eddy variance (via increased barotropic instability) and increase in subsurface mean kinetic energy along the length of the EAC. The response of EAC separation to regional variable wind stress has important implications for both past and future climate change studies.
Apoptogenic effects of β-sitosterol glucoside from Castanopsis indica leaves.
Dolai, Narayan; Kumar, Ashish; Islam, Aminul; Haldar, Pallab K
2016-01-01
β-Sitosterol glucoside (BSSG) is a natural biologically active substance isolated from the Castanopsis indica leaves. This study explored the apoptogenic mechanistic studies of BSSG against Ehrlich's ascites carcinoma (EAC) treated mice through morphological study, comet assay, flow cytometry (FACS) and Western blotting assay method. AO/EB staining and FACS analysis showed that BSSG possessed apoptosis induction activities on EAC cells. Dose dependent induction of DNA damage was observed after BSSG treatment. Increase the expression of apoptotic protein p53 and p21 in EAC, multiple downstream factors contributing to apoptosis pathway. The increase of caspase-9 and caspase-3 activities revealed that caspase was a key mediator of the apoptotic pathway induced by BSSG, and up-regulation of Bax and down-regulation of anti-apoptotic protein Bcl-2 resulted in the decrease of Bcl-2/Bax ratio. Owing to the combination of significant antitumour activity by inducing apoptosis, BSSG holds the promise of being an interesting chemo-preventive agent active in cancer therapy.
Lubin, Jay H; Cook, Michael B; Pandeya, Nirmala; Vaughan, Thomas L; Abnet, Christian C; Giffen, Carol; Webb, Penelope M; Murray, Liam J; Casson, Alan G; Risch, Harvey A; Ye, Weimin; Kamangar, Farin; Bernstein, Leslie; Sharp, Linda; Nyrén, Olof; Gammon, Marilie D; Corley, Douglas A; Wu, Anna H; Brown, Linda M; Chow, Wong-Ho; Ward, Mary H; Freedman, Neal D; Whiteman, David C
2012-06-01
Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. The authors pooled data from 12 case-control studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01). Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases. Published by Elsevier Ltd.
Endocrine active contaminants in aquatic systems and intersex in common sport fishes
Lee Pow, Crystal S. D.; Law, J. Mac; Kwak, Thomas J.; Cope, W. Gregory; Rice, James A.; Kullman, Seth W.; Aday, D. Derek
2017-01-01
Male fish are susceptible to developing intersex, a condition characterized by the presence of testicular oocytes. In the present study, the relationship between intersex and exposure to estrogenic endocrine active contaminants (EACs) was assessed for 2 genera of sport fish, Micropterus and Lepomis, at 20 riverine sites. Seasonal trends and relationships between EACs and intersex (prevalence and severity) were examined at varying putative sources of EACs throughout North Carolina, identified as point sources, nonpoint sources, and reference sites. Intersex was identified in both genera, which was documented for the first time in wild-caught Lepomis. Intersex was more prevalent (59.8%) and more severe (1.6 mean rank) in Micropterus, which was highly correlation to EACs in sediment. In contrast, intersex was less common (9.9%) and less severe (0.2 mean rank) in Lepomis and was highly correlated to EACs in the water column. The authors found that concentrations of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, industrial EACs, and estrogens were highest at point source sites; however, no source type variation was identified in the prevalence or severity of intersex, nor were there seasonal trends in intersex or EAC concentrations. The authors’ results associate genus-specific prevalence of intersex with specific EAC classes in common sport fishes having biological, ecological, and conservation implications.
Material Issues of Blanket Systems for Fusion Reactors - Compatibility with Cooling Water -
NASA Astrophysics Data System (ADS)
Miwa, Yukio; Tsukada, Takashi; Jitsukawa, Shiro
Environmental assisted cracking (EAC) is one of the material issues for the reactor core components of light water power reactors(LWRs). Much experience and knowledge have been obtained about the EAC in the LWR field. They will be useful to prevent the EAC of water-cooled blanket systems of fusion reactors. For the austenitic stainless steels and the reduced-activation ferritic/martensitic steels, they clarifies that the EAC in a water-cooled blanket does not seem to be acritical issue. However, some uncertainties about influences on water temperatures, water chemistries and stress conditions may affect on the EAC. Considerations and further investigations elucidating the uncertainties are discussed.
Mitcham, Carl; Englehardt, Elaine E
2016-08-22
The movements to teach the responsible conduct of research (RCR) and engineering ethics at technological universities are often unacknowledged aspects of the ethics across the curriculum (EAC) movement and could benefit from explicit alliances with it. Remarkably, however, not nearly as much scholarly attention has been devoted to EAC as to RCR or to engineering ethics, and RCR and engineering ethics educational efforts are not always presented as facets of EAC. The emergence of EAC efforts at two different institutions-the Illinois Institute of Technology and Utah Valley University (UVU)-provide counter examples. The remarkably successful UVU initiative gave birth to EAC as a scholarly movement and to the associated Society for Ethics Across the Curriculum. EAC initiatives at the Colorado School of Mines, however, point up continuing institutional resistances to EAC. Finally, comparative reflection on successes and failures can draw some lessons for the future. One suggestion is that increasing demands for accountability and pedagogical research into what works in teaching and learning offers special opportunities.
Binnetoglu, A; Sari, M; Baglam, T; Erbarut Seven, I; Yumusakhuylu, A C; Topuz, M F; Batman, C
2015-08-01
Fascin is an actin-bundling protein found in cell membrane protrusions and increases cell motility. The expression of fascin in epithelial neoplasms has been described only recently. No data are available concerning the role of this protein in invasive cholesteatoma. Thus, we investigated the expression of fascin in cholesteatoma tissue and the relationship between fascin expression and intraoperative evaluation of the destruction of the ossicular chain and extent of disease. Cholesteatoma specimens of 28 patients and external auditory canal (EAC) skin specimens of the same patients (as the control group) were collected from mastoidectomies. Immunohistochemical technique was used to investigate the fascin expression in all cholesteatoma tissues and EAC skin specimens. Immunohistochemical staining was assessed semiquantitatively based on the thickness of epithelium. SPSS software version 16.0 (SPSS Inc., Chicago, IL, USA) was performed to statistically analyse the relationships between fascin expression and intraoperative evaluation destruction of ossicular chain and extent of the disease. Immunohistochemically, there was no or very low fascin expression observed in normal epithelial cells of EAC skin, while expressed in cholesteatoma tissue. Also, fascin expression in cholesteatoma tissues was significantly correlated with destruction of ossicular chain and extent of the disease. Fascin expression is usually found in cholesteatoma epithelium and is correlated with destruction of the ossicular chain and extent of disease. Considering all of the correlations between the clinical and histopathological findings, 'fascin immunoexpression scoring' may be used for histological grading of cholesteatoma. © 2015 John Wiley & Sons Ltd.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-09
... provisions of the Administrative Procedures Act (APA). It is a voluntary effort by the EAC to gather input... the APA's rulemaking provisions applicable to development of this or future EAC procedural programs...
Samanta, S; Pain, A; Dutta, S; Sanyal, U
2001-01-01
New mixed function anticancer compounds as 2-chloroethylnitrosoureas of substituted naphthalimides represented by bromonap-NU 4a and chloronap-NU 4b, have been synthesized from 4-bromo- and 4-chloro-l,8-naphthalic anhydride, respectively following a 3-step process. Their chemical alkylating activity compared with nor -HN2 indicated that they possess greater alkylating activity than the latter. Their antitumour efficacies were assessed in vivo in two murine ascites tumours, namely Ehrlich ascites carcinoma (EAC) and Sarcoma-180 (S-180) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Two standard clinical drugs namely endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Both of them have displayed substantial and reproducible antitumoral activity in these tumours comparable with 5-FU. These were further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines.
Evaluation of dimethoxydop-NU as a novel anti-tumor agent.
Mukherjee, A; Dutta, S; Sanyal, U
2007-12-01
Dimethoxydop-NU, 1-[2-{3-(2-Chloroethyl)-3-nitrosoureido}ethyl]-3,4-dimethoxy-benzene (Compound 1), was synthesized from 3,4-dimethoxy-phenethylamine as a novel anti-tumor agent based on the structures of the clinical drug CCNU and dopamine, an important endogenous biological amine having anti-angiogenesis property. In vitro screening in two human tumor cell lines, namely promyelocytic leukemia HL-60 and histiocytic lymphoma U-937, revealed its cytotoxicity greater than that of hydroxyurea and comparable to BCNU used as standards. Its in vivo anti-tumoral potency was assessed in the murine ascites tumors Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times of drug treated (T) over untreated control (C) mice. Results revealed significant tumor regression effects in these tumors. The survival time of treated mice was markedly increased by combination of the compound 1 with dopamine hydrochloride. Its toxicity was assessed in vivo in normal and EAC bearing mice by measuring drug-induced changes in hematological parameters, femoral bone marrow and splenic cellularities as well as biochemical parameters sequentially on days 9, 14 and 19 following drug treatment at the optimum dose of 30 mg/kg from day 1 to 7. Results indicated that initial suppression in the femoral bone marrow cellularity seen on day 9 reached normalcy by day 19. Other parameters were within normal limit. Histopathological studies of liver revealed mild hepatotoxicity on day 9 in treated groups that substantially recovered on day 19. Similar studies with heart and kidney revealed no cardio toxicity or nephrotoxicity. Compound 1 comparable to standards inhibited the synthesis of DNA and RNA in S-180 tumor cells.
In vivo anticancer activity of vanillin semicarbazone
Ali, Shaikh M Mohsin; Azad, M Abul Kalam; Jesmin, Mele; Ahsan, Shamim; Rahman, M Mijanur; Khanam, Jahan Ara; Islam, M Nazrul; Shahriar, Sha M Shahan
2012-01-01
Objective To evaluate the anticancer activity of vanillin semicarbazone (VSC) against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. Methods The compound VSC at three doses (5, 7.5 and 10 mg/kg i.p.) was administered into the intraperitoneal cavity of the EAC inoculated mice to observe its efficiency by studying the cell growth inhibition, reduction of tumour weight, enhancement of survival time as well as the changes in depleted hematological parameters. All such parameters were also studied with a known standard drug bleomycin at the dose of 0.3 mg/kg (i.p.). Results Among the doses studied, 10 mg/kg (i.p.) was found to be quite comparable in potency to that of bleomycin at the dose of 0.3 mg/kg (i.p.). The host toxic effects of VSC was found to be negligible. Conclusions It can be concluded that VSC can therefore be considered as potent anticancer agent. PMID:23569946
Soliman, Amel M; Fahmy, Sohair R; El-Abied, Salma A
2015-01-01
Objectives: With the development of sophisticated instruments for the isolation and elucidation of natural products structures from marine and freshwater organisms, major advances have been made in the discovery of aquatic derived therapeutics. Present investigations were carried out to evaluate cuttlefish (Sepia officinalis) ink extract (IE) and freshwater clam (Coelatura aegyptiaca) extract (CE) for their anticancer and antioxidant activities as compared to 5-flurouracil (5-Fu), in Ehrlich ascites carcinoma (EAC). Methods: Sixty female Swiss albino mice were divided into five groups (n = 12). All groups except group I received EAC cells (5 × 106 cells/mouse i.p.) and this was taken as the 0th day. Group I served as saline control (5 ml/kg 0.9% NaCl w/v p.o). Group II served as EAC control. Rats of groups III, IV and V received IE, CE (200 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.), respectively. Results: The reduction in tumor volume, packed cell volume, tumor cell counts and increase in median survival time and percentage increase in life span in treated animals were observed. There was a significant increase in RBC count; Hb content in treated animals and reduction in total WBC count. There was a significant decrease in AST, ALT, ALP and liver MDA levels and increase in GSH, SOD and NO levels were observed in all treated animals. Conclusion: Both IE and CE were effective in inhibiting the tumor growth in ascitic tumor models. The biochemical, antioxidants and histopathological studies were also supported their antitumor properties. PMID:26097537
BACKGROUND: An in vitro steroidogenesis assay using the human adrenocortical carcinoma cells H295R is being evaluated as a possible toxicity screening approach to detect and assess the impact of endocrine active chemicals (EAC) capable of altering steroid biosynthesis. Interpreta...
Dong, Jing; Buas, Matthew F; Gharahkhani, Puya; Kendall, Bradley J; Onstad, Lynn; Zhao, Shanshan; Anderson, Lesley A; Wu, Anna H; Ye, Weimin; Bird, Nigel C; Bernstein, Leslie; Chow, Wong-Ho; Gammon, Marilie D; Liu, Geoffrey; Caldas, Carlos; Pharoah, Paul D; Risch, Harvey A; Iyer, Prasad G; Reid, Brian J; Hardie, Laura J; Lagergren, Jesper; Shaheen, Nicholas J; Corley, Douglas A; Fitzgerald, Rebecca C; Whiteman, David C; Vaughan, Thomas L; Thrift, Aaron P
2018-04-01
We developed comprehensive models to determine risk of Barrett's esophagus (BE) or esophageal adenocarcinoma (EAC) based on genetic and non-genetic factors. We used pooled data from 3288 patients with BE, 2511 patients with EAC, and 2177 individuals without either (controls) from participants in the international Barrett's and EAC consortium as well as the United Kingdom's BE gene study and stomach and esophageal cancer study. We collected data on 23 genetic variants associated with risk for BE or EAC, and constructed a polygenic risk score (PRS) for cases and controls by summing the risk allele counts for the variants weighted by their natural log-transformed effect estimates (odds ratios) extracted from genome-wide association studies. We also collected data on demographic and lifestyle factors (age, sex, smoking, body mass index, use of nonsteroidal anti-inflammatory drugs) and symptoms of gastroesophageal reflux disease (GERD). Risk models with various combinations of non-genetic factors and the PRS were compared for their accuracy in identifying patients with BE or EAC using the area under the receiver operating characteristic curve (AUC) analysis. Individuals in the highest quartile of risk, based on genetic factors (PRS), had a 2-fold higher risk of BE (odds ratio, 2.22; 95% confidence interval, 1.89-2.60) or EAC (odds ratio, 2.46; 95% confidence interval, 2.07-2.92) than individual in the lowest quartile of risk based on PRS. Risk models developed based on only demographic or lifestyle factors or GERD symptoms identified patients with BE or EAC with AUC values ranging from 0.637 to 0.667. Combining data on demographic or lifestyle factors with data on GERD symptoms identified patients with BE with an AUC of 0.793 and patients with EAC with an AUC of 0.745. Including PRSs with these data only minimally increased the AUC values for BE (to 0.799) and EAC (to 0.754). Including the PRSs in the model developed based on non-genetic factors resulted in a net reclassification improvement for BE of 3.0% and for EAC of 5.6%. We used data from 3 large databases of patients from studies of BE or EAC to develop a risk prediction model based on genetic, clinical, and demographic/lifestyle factors. We identified a PRS that increases discrimination and net reclassification of individuals with vs without BE and EAC. However, the absolute magnitude of improvement is not sufficient to justify its clinical use. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Juth, Vanessa; Dickerson, Sally S.; Zoccola, Peggy M.; Lam, Suman
2015-01-01
Background Dispositional emotional approach coping (EAC) marks an adaptive tendency to process and express emotions. EAC’s association with cognitions, affect, and intra- and interindividual characteristics that may account for its utility was examined in response to an acute stressor and in daily life. Design This study included a laboratory stress task and ecological momentary assessment. Methods Healthy undergraduate students (n = 124; mean age: 20; women: 56%) completed a laboratory component (baseline survey, speech stress task, pre- and posttask measures) and five subsequent days of surveys via palm pilot (six surveys/day). Results Controlling for sex, neuroticism, and social support, greater EAC was associated with more positive cognitive appraisals, personal resources, and positive affect and less-negative affect during the lab stressor, and with more perceived control and positive affect in daily life. Significant EAC × sex interactions were found for poststressor affect: men with high EAC reported more positive affect and women with high EAC reported less negative affect. Conclusions Findings provide support that EAC’s utility may be independent of intra- and interindividual characteristics, and that men and women may benefit from EAC in different ways in regards to affect. The proclivity to use EAC may come with a resiliency that protects against stress and promotes general well-being. PMID:24804564
Relation of contaminants to fish intersex in riverine sport fishes.
Grieshaber, Casey A; Penland, Tiffany N; Kwak, Thomas J; Cope, W Gregory; Heise, Ryan J; Law, J Mac; Shea, Damian; Aday, D Derek; Rice, James A; Kullman, Seth W
2018-06-20
Endocrine active compounds (EACs) are pollutants that have been recognized as an emerging and widespread threat to aquatic ecosystems globally. Intersex, the presence of female germ cells within a predominantly male gonad, is considered a biomarker of endocrine disruption caused by EACs. We measured a suite of EACs and assessed their associated impacts on fish intersex occurrence and severity in a large, regulated river system in North Carolina and South Carolina, USA. Our specific objective was to determine the relationship of contaminants in water, sediment, and fish tissue with the occurrence and severity of the intersex condition in wild, adult black bass (Micropterus), sunfish (Lepomis), and catfish (Ictaluridae) species at 11 sites located on the Yadkin-Pee Dee River. Polycyclic aromatic hydrocarbons (PAHs), ethinylestradiol (EE2), and heavy metals were the most prevalent contaminants that exceeded effect levels for the protection of aquatic organisms. Fish intersex condition was most frequently observed and most severe in black basses and was less frequently detected and less severe in sunfishes and catfishes. The occurrence of the intersex condition in fish showed site-related effects, rather than increasing longitudinal trends from upstream to downstream. Mean black bass and catfish tissue contaminant concentrations were higher than that of sunfish, likely because of the latter's lower trophic position in the food web. Principal component analysis identified waterborne PAHs as the most correlated environmental contaminant with intersex occurrence and severity in black bass and sunfish. As indicated by the intersex condition, EACs have adverse but often variable effects on the health of wild sport fishes in this river, likely due to fluctuations in EAC inputs and the dynamic nature of the riverine system. These findings enhance the understanding of the relationship between contaminants and fish health and provide information to guide ecologically comprehensive conservation and management decisions. Copyright © 2018 Elsevier B.V. All rights reserved.
75 FR 39224 - Sunshine Act Notice
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2010-07-08
.... ACTION: Notice of Virtual Public Meeting for EAC Standards Board. DATE AND TIME: Tuesday, July 27, 2010, 1-7 p.m. edt PLACE: The EAC Standards Board Virtual Public Meeting will be webcast live from the U.S...:// www.eac.gov and click the link to the Standards Board Virtual Public Meeting. AGENDA: The U.S...
A Structure Standard for Archival Context: EAC-CPF Is Here
ERIC Educational Resources Information Center
Dryden, Jean
2010-01-01
The archival community's new descriptive standard, "Encoded Archival Context" for Corporate Bodies, Persons, and Families (EAC-CPF), supports the sharing of descriptions of records creators and is a significant addition to the suite of standards for archival description. EAC-CPF is a data structure standard similar to its older sibling EAD…
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2013-04-16
... System Test Laboratories Program Manual, Version 2.0 AGENCY: United States Election Assistance Commission (EAC). ACTION: Notice; publication of Voting System Test Laboratories Program Manual, Version 2.0, for 60 day public comment period on EAC Web site. SUMMARY: The U.S. Election Assistance Commission (EAC...
Effect of Chelating Agents on the Stability of Nano-TiO2 Sol Particles for Sol-Gel Coating.
Maeng, Wan Young; Yoo, Mi
2015-11-01
Agglomeration of sol particles in a titanium alkoxide (tetrabutyl orthotitanate (TBOT), > 97%) solution during the hydrolysis and condensation steps makes the sol solution difficult to use for synthesizing homogeneous sol-gel coating. Here, we have investigated the effect of stabilizing agents (acetic acid and ethyl acetoacetate (EAcAc)) on the agglomeration of Ti alkoxide particles during hydrolysis and condensation in order to determine the optimized conditions for controlling the precipitation of TiO2 particles. The study was conducted at R(AC) ([acetic acid]/[TBOT]) = 0.1-5 and R(EAcAc)([EAcAc]/[TBOT]) = 0.05-0.65. We also studied the effects of a basic catalyst ethanolamine (ETA), water, and HCl on sol stability. The chelating ligands in the precursor sol were analyzed with FT-IR. The coating properties were examined by focused ion beam. The stabilizing agents (acetic acid and EAcAc) significantly influenced the agglomeration and precipitation of TBOT precursor particles during hydrolysis. As R(AC) and R(EAcAc) increased, the agglomeration remarkably decreased. The stability of the sol with acetic acid and EAcAc arises from the coordination of the chelating ligand to TBOT that hinders hydrolysis and condensation. A uniform fine coating (thickness: 30 nm) on stainless steel was obtained by using an optimized sol with R(AC) = 0.5 and R(EAcAc) = 0.65.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-06
... for Version 1.1 of the Voluntary Voting System Guidelines (VVSG) AGENCY: United States Election... Voluntary Voting System Guidelines (VVSG). SUMMARY: The Help America Vote Act of 2002 (HAVA) (Pub. L. 107... (EAC). Section 202 of HAVA directs the EAC to adopt voluntary voting system guidelines (VVSG) and to...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-06
... for free movement of goods, labor, services and capital among the EAC member countries. In June 2011... private sector ties between companies in the United States and the EAC and throughout the EAC region; and... Dialogue. First, Commerce plans to propose the promotion of business opportunities in key growth sectors...
Aranha, Maria F. M.; Müller, Cristina E. E.; Gavião, Maria B. D.
2015-01-01
BACKGROUND: Acupuncture stimulates points on the body, influencing the perception of myofascial pain or altering physiologic functions. OBJECTIVE: The aim was to evaluate the effect of electroacupuncture (EAC) and acupuncture (AC) for myofascial pain of the upper trapezius and cervical range of motion, using SHAM acupuncture as control. METHOD: Sixty women presenting at least one trigger point at the upper trapezius and local or referred pain for more than six months were randomized into EAC, AC, and SHAM groups. Eight sessions were scheduled and a follow-up was conducted after 28 days. The Visual Analog Scale assessed the intensity of local and general pain. A fleximeter assessed cervical movements. Data were analyzed using paired t or Wilcoxon's tests, ANOVA or Friedman or Kruskal-Wallis tests and Pearson's correlation (α=0.05). RESULTS: There was reduction in general pain in the EAC and AC groups after eight sessions (P<0.001). A significant decrease in pain intensity occurred for the right trapezius in all groups and for the left trapezius in the EAC and AC groups. Intergroup comparisons showed improvement in general pain in the EAC and AC groups and in local pain intensity in the EAC group (P<0.05), which showed an increase in left rotation (P=0.049). The AC group showed increases in inclination (P=0.005) sustained until follow-up and rotation to the right (P=0.032). CONCLUSION : EAC and AC were effective in reducing the pain intensity compared with SHAM. EAC was better than AC for local pain relief. These treatments can assist in increasing cervical range of motion, albeit subtly. PMID:25714602
Environment-Assisted Cracking in Custom 465 Stainless Steel
NASA Astrophysics Data System (ADS)
Lee, E. U.; Goswami, R.; Jones, M.; Vasudevan, A. K.
2011-02-01
The influence of cold work and aging on the environment-assisted cracking (EAC) behavior and mechanical properties of Custom 465 stainless steel (SS) was studied. Four sets of specimens were made and tested. All specimens were initially solution annealed, rapidly cooled, and refrigerated (SAR condition). The first specimen set was steel in the SAR condition. The second specimen set was aged to the H1000 condition. The third specimen set was 60 pct cold worked, and the fourth specimen set was 60 pct cold worked and aged at temperatures ranging from 755 K to 825 K (482 °C to 552 °C) for 4 hours in air. The specimens were subsequently subjected to EAC and mechanical testing. The EAC testing was conducted, using the rising step load (RSL) technique, in aqueous solutions of NaCl of pH 7.3 with concentrations ranging from 0.0035 to 3.5 pct at room temperature. The microstructure, dislocation substructure, and crack paths, resulting from the cold work, aging, or subsequent EAC testing, were examined by optical microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The aging of the cold-worked specimens induced carbide precipitation within the martensite lath, but not at the lath or packet boundaries. In the aged specimens, as aging temperature rose, the threshold stress intensity for EAC (KIEAC), elongation, and fracture toughness increased, but the strength and hardness decreased. The KIEAC also decreased with increasing yield strength and NaCl concentration. In the SAR and H1000 specimens, the EAC propagated along the prior austenite grain boundary, while in the cold-worked and cold-worked and aged specimens, the EAC propagated along the martensite lath, and its packet and prior austenite grain boundaries. The controlling mechanism for the observed EAC was identified to be hydrogen embrittlement.
NASA Astrophysics Data System (ADS)
Archer, Matthew R.; Roughan, Moninya; Keating, Shane R.; Schaeffer, Amandine
2017-11-01
Given the importance of western boundary currents over a wide range of scales in the ocean, it is crucial that we understand their dynamics to accurately predict future changes. For this, we need detailed knowledge of their structure and variability. Here we investigate the jet structure of the East Australian Current (EAC), using observations from HF radars and moorings deployed at 30°S-31°S. Meandering, core velocity, width, and eddy kinetic energy (EKE) are quantified from 4 years of hourly 1.5 km resolution surface current maps (2012-2016), to obtain the most detailed representation of the surface EAC jet to date. The EAC flows predominantly over the ˜1,500 m isobath 50 km offshore but makes large amplitude displacements eastward every 65-100 days—the time scale associated with mesoscale eddy shedding at the EAC separation. Smaller-amplitude, higher-frequency meanders occur every 20-45 days. Using a coordinate frame that follows the jet, we show core velocity and EKE exhibit seasonality in both magnitude and variance, being maximum in summer (1.55 m s-1 mean core velocity), minimum in winter (0.8 m s-1). However, it is the eddy-shedding time scale that dominates jet variability. As the EAC moves shoreward, shelf temperature and along-stream velocity vary linearly with jet movement, within ˜35 km of the core. The EAC is within this range 75% of the time, demonstrating its importance to the shelf circulation. Temperature and velocity fluctuations at the 70 m (100 m) isobath are more influenced by wind (EAC encroachment), with the strongest response occurring when wind and EAC act constructively.
Bilateral acquired external auditory canal stenosis with squamous papilloma: a case report.
Demirbaş, Duygu; Dağlı, Muharrem; Göçer, Celil
2011-01-01
Acquired external auditory canal (EAC) stenosis is described as resulting from a number of different causes such as infection, trauma, neoplasia, inflammation and radiotherapy. Human papilloma virus (HPV) type 6, a deoxyribonucleic acid (DNA) virus, is considered to cause squamous papilloma of the EAC. In this article, we report a case of a 56-year-old male with warty lesions in the left external ear and a totally stenotic right external ear which had similar lesions one year before the involvement of his left ear. On computed tomography of the temporal bone, there was soft tissue obstruction of the right EAC, and thickening in the skin of the left EAC. The middle ear structures were normal on both sides. Biopsy was performed from the lesion in the left ear, and revealed squamous papilloma. We presented this case because squamous papilloma related bilateral acquired EAC stenosis is a rare entity.
Esophageal adenocarcinoma and Barrett esophagus in a neurologically impaired teenager.
Hwang, Jae-Yeon; Lee, Yeoun Joo; Chun, Peter; Shin, Dong Hoon; Park, Jae Hong
2016-11-01
Esophageal adenocarcinoma (EAC) accompanied by Barrett esophagus (BE) is rare in patients younger than 20 years old. EAC in the upper esophagus is also rare. We report a rare case of EAC with BE that developed in the upper esophagus after chronic, untreated gastroesophageal reflux disease in a neurologically impaired teenager. A 19-year-old neurologically impaired man underwent endoscopy for evaluation of dysphagia and vomiting, and was diagnosed with EAC with BE. He underwent transthoracic esophagectomy, extensive lymph node dissection, and cervical esophagogastric anastomosis, but the prognosis was poor. Pathology indicated poorly differentiated adenocarcinoma with BE. © 2016 Japan Pediatric Society.
In vivo over-expression of KGF mimic human middle ear cholesteatoma.
Yamamoto-Fukuda, Tomomi; Akiyama, Naotaro; Shibata, Yasuaki; Takahashi, Haruo; Ikeda, Tohru; Koji, Takehiko
2015-10-01
We reported previously that keratinocyte growth factor (KGF), a mesenchymal cell-derived paracrine growth factor, plays an important role in middle ear cholesteatoma formation, which is characterized by marked proliferation of epithelial cells. Here, we investigated whether KGF, the main factor that induces cholesteatoma, overexpression in vivo results in the formation of cholesteatoma. Flag-hKGF cDNA driven by CMV14 promoter was transfected through electroporation into the external auditory canal (EAC) of rats once (short-term model) or five times on every fourth day (long-term model). Ears transfected with empty vector were used as controls. Successful transfection of plasmids into epithelial and stromal cells was confirmed by Flag immunohistochemistry. In the short-term model, the intensity of KGF protein was the strongest in hKGF transfected ear at day 4. KGF expression induced epithelial cell proliferation, reaching a peak level at day 4 and then decreased later, while in the long-term model, KGF expression in the EAC led to middle ear cholesteatoma formation. In conclusion, we described here a new experimental model of human middle ear cholesteatoma, and demonstrated that KGF and KGF receptor paracrine action play an essential role in middle ear cholesteatoma formation in an in vivo model.
Modulation of estrogenic action in clear cell carcinoma of the ovary (Review)
TANASE, YASUHITO; YAMADA, YOSHIHIKO; SHIGETOMI, HIROSHI; KAJIHARA, HIROTAKA; OONOGI, AKIRA; YOSHIZAWA, YORIKO; FURUKAWA, NAOTO; HARUTA, SHOJI; YOSHIDA, SHOZO; SADO, TOSHIYUKI; OI, HIDEKAZU; KOBAYASHI, HIROSHI
2012-01-01
Two histologic types, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC), are the common histology in ovarian cancer patients who have associated endometriosis. However, both tumor types have distinct clinicopathological characteristics and molecular phenotypes. EAC is predominantly positive for estrogen receptor (ER), but CCC specifically exhibits lower ER expression. This study reviews the current understanding of the role of the ER information in the pathogenesis of CCC, as well as the English language literature for biochemical studies on ER expression and estrogenic action in CCC. The iron-mediated oxidative stress occurs due to repeated hemorrhage in endometriosis, then this compound oxidatively modifies genomic DNA and, subsequently, ER depletion may be observed. There are a number of factors that interfere with ER expression and estrogen activity, which include DNA methylation of the promoter region, histone deacetylation, heme and iron binding, chromatin remodeling and ubiquitin ligase activity. Loss of estrogen function may be a turning point in CCC progression and aggressiveness. PMID:22969838
Corrosion fatigue of alloys 600 and 690 in simulated LWR environments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ruther, W.E.; Soppett, W.K.; Kassner, T.F.
1996-04-01
Crack growth data were obtained on fracture-mechanics specimens of Alloys 600 and 690 to investigate environmentally assisted cracking (EAC) in simulated boiling water reactor and pressurized water reactor environments at 289 and 320 C. Preliminary information was obtained on the effect of temperature, load ratio, stress intensity (K), and the dissolved-oxygen and -hydrogen concentrations of the water on EAC. Specimens of Type 316NG and sensitized Type 304 stainless steel (SS) were included in several of the experiments to assess the behavior of these materials and Alloy 600 under the same water chemistry and loading conditions. The experimental data are comparedmore » with predictions from an Argonne National Laboratory (ANL) model for crack growth rates (CGRs) of SSs in water and the ASME Code Section 11 correlation for CGRs in air at the K{sub max} and load-ratio values in the various tests. The data for all of the materials were bounded by ANL model predictions and the ASME Section 11 ``air line.``« less
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2012-10-01
... Administrative Procedures Act (APA). It is a voluntary effort by the EAC to gather input from the public on the.... Furthermore, this request by the EAC for public comment is not intended to make any of the APA's rulemaking... 2005 VVSG (also known as VVSG 1.0) as a result of feedback received through its Voting System Testing...
Thein, Hla-Hla; Jembere, Nathaniel; Thavorn, Kednapa; Chan, Kelvin K W; Coyte, Peter C; de Oliveira, Claire; Hur, Chin; Earle, Craig C
2018-06-27
Esophageal adenocarcinoma (EAC) incidence is increasing rapidly. Esophageal cancer has the second lowest 5-year survival rate of people diagnosed with cancer in Canada. Given the poor survival and the potential for further increases in incidence, phase-specific cost estimates constitute an important input for economic evaluation of prevention, screening, and treatment interventions. The study aims to estimate phase-specific net direct medical costs of care attributable to EAC, costs stratified by cancer stage and treatment, and predictors of total net costs of care for EAC. A population-based retrospective cohort study was conducted using Ontario Cancer Registry-linked administrative health data from 2003 to 2011. The mean net costs of EAC care per 30 patient-days (2016 CAD) were estimated from the payer perspective using phase of care approach and generalized estimating equations. Predictors of net cost by phase of care were based on a generalized estimating equations model with a logarithmic link and gamma distribution adjusting for sociodemographic and clinical factors. The mean net costs of EAC care per 30 patient-days were $1016 (95% CI, $955-$1078) in the initial phase, $669 (95% CI, $594-$743) in the continuing care phase, and $8678 (95% CI, $8217-$9139) in the terminal phase. Overall, stage IV at diagnosis and surgery plus radiotherapy for EAC incurred the highest cost, particularly in the terminal phase. Strong predictors of higher net costs were receipt of chemotherapy plus radiotherapy, surgery plus chemotherapy, radiotherapy alone, surgery alone, and chemotherapy alone in the initial and continuing care phases, stage III-IV disease and patients diagnosed with EAC later in a calendar year (2007-2011) in the initial and terminal phases, comorbidity in the continuing care phase, and older age at diagnosis (70-74 years), and geographic region in the terminal phase. Costs of care vary by phase of care, stage at diagnosis, and type of treatment for EAC. These cost estimates provide information to guide future resource allocation decisions, and clinical and policy interventions to reduce the burden of EAC.
Development of differential cytotoxic compounds containing nitrosourea and benzothiazine nucleus.
Nyati, M K; Rai, D; Gupta, R R; Dev, P K
1997-01-01
The in vivo activity of 4 new benzothiazinyl-nitrosourea compounds was investigated against Sarcoma-180 (S-180) and Ehrlich Ascitic Carcinoma (EAC) induced ascitic and solid tumors. EAC solid tumor was found to be the most sensitive, where one compound (no 4) inhibited tumor growth to only 3 per cent of the control value. All the 4 compounds tested were found to be toxicologically more selective than 5-fluorouracil and 6-mercaptopurine drugs. The reason for this selective toxicity may be attributed to the inhibition of isocyanate moiety in these compounds which causes toxicity to normal cells via a carbamoylation reaction. However, they may still remain potent, since they decompose into an alkylating carbonium species and a charge transfer complex which may interact with DNA via alkylation and intercalation reactions, respectively.
NASA Astrophysics Data System (ADS)
Knorr, Klaus-Holger; Gao, Chuanyu; Agethen, Svenja; Sander, Michael
2017-04-01
To understand carbon storage in water logged, anaerobic peatlands, factors controlling mineralization have been studied for decades. Temperature, substrate quality, water table position and the availability of electron acceptors for oxidation of organic carbon have been identified as major factors. However, many studies reported an excess carbon dioxide (CO2) production over methane (CH4) that cannot be explained by available electron acceptors, and peat soils did not reach strictly methanogenic conditions (i.e., a stoichiometric formation ratio of 1:1 of CO2 to CH4). It has been hypothesized that peat organic matter (OM) provides a previously unrecognized electron acceptor for microbial respiration, elevating CO2 to CH4 ratios. Microbial reduction of dissolved OM has been shown in the mid 90's, but only recently mediated electrochemical techniques opened the possibility to access stocks and changes in electron accepting capacities (EAC) of OM in dissolved and solid form. While it was shown that the EAC of OM follows redox cycles of microbial reduction and O2 reoxidation, changes in the EAC of OM were so far not related quantitatively to CO2 production. We therefore tested if CO2 production in anoxic peat incubations is balanced by the consumption of electron acceptors if EAC of OM is included. We set up anoxic incubations with peat and monitored production of CO2 and CH4, and changes in EAC of OM in the dissolved and solid phase over time. Interestingly, in all incubations, the EAC of dissolved OM was poorly related to CO2 and CH4 production. Instead, dissolved OM was rapidly reduced at the onset of the incubations and thereafter remained in reduced form. In contrast, the decrease in the EAC of particulate (i.e. non-dissolved) OM was closely linked to the observed production of non-methanogenic CO2. Thereby, the total EAC of the solid OM pool by far exceeded the EAC of the dissolved OM pool. Over the course of eight week incubations, measured decreases in the EAC of total NOM could explain 22-38 % of excess CO2 production in a weakly decomposed peat, 30-67 % of excess CO2 production in a well decomposed peat, and >100 % of excess CO2 production in a peat that had been exposed to oxygen for > 1 year. In this latter peat, EAC by OM explained 45-57 % of CO2 production, while reduction of sulfate available in this material readily explained the remaining fraction. Despite having considerable uncertainty arising from methodological challenges, the collected data demonstrated that accounting for the EACs of solid and dissolved OM may fully explain excess CO2 production. As we conservatively assumed a carbon oxidation state of zero for our budget calculations, a higher oxidation state of C in NOM as suggested by elemental analysis would result in electron equivalent budgets between EAC decreases and CO2 formation even closer to 100 %. A higher oxidation state of mineralized carbon seemed especially likely for weakly decomposed peat, as this material had higher concentrations of oxygen and showed the largest percentage of formed CO2 that could not be explained based on OM reduction.
Zhang, Qian; Ullah, Shakeeb; Liu, Yi; Yang, Ping; Chen, Bing; Waqas, Yasir; Bao, Huijun; Hu, Lisi; Li, Quanfu; Chen, Qiusheng
2016-01-01
The structural characteristics of the splenic sheathed capillary were investigated using light microscopy and transmission electron microscopy (TEM). This study mainly focused on lymphocyte migration to the splenic white pulp via micro-channels in Chinese soft-shelled turtles, Pelodiscus sinensis. The results showed that the sheathed capillaries in the turtle spleen were high endothelial venule (HEV)-like vessels. These capillaries consist of micro-channels that facilitate lymphocyte migration to the splenic white pulp. The micro-channel is a dynamic structure comprising processes of endothelial cells, supporting cells, and ellipsoid-associated cells (EACs), which provides a microenvironment for lymphocyte migration. The pattern of lymphocyte migration in the micro-channel of the turtle spleen includes the following steps: (i) lymphocyte first adheres to the endothelium of the sheathed capillary, passes through the endothelial cells, and traverses through the basement membrane of the sheathed capillary; (ii) it then enters into the ellipsoid combined with supporting cells and EACs; and (iii) lymphocyte migrates from the ellipsoid to the periellipsoidal lymphatic sheath (PELS) via the micro-channel. This study provides morphological evidence for lymphocyte migration in the micro-channels of turtle spleens and also an insight into the mechanism of lymphocyte homing to the splenic white pulp of reptiles. Copyright © 2015 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Bull, Christopher Y. S.; Kiss, Andrew E.; van Sebille, Erik; Jourdain, Nicolas C.; England, Matthew H.
2018-02-01
The East Australian Current (EAC) plays a major role in regional climate, circulation, and ecosystems, but predicting future changes is hampered by limited understanding of the factors controlling EAC separation. While there has been speculation that the presence of New Zealand may be important for the EAC separation, the prevailing view is that the time-mean partial separation is set by the ocean's response to gradients in the wind stress curl. This study focuses on the role of New Zealand, and the associated adjacent bathymetry, in the partial separation of the EAC and ocean circulation in the Tasman Sea. Here utilizing an eddy-permitting ocean model (NEMO), we find that the complete removal of the New Zealand plateau leads to a smaller fraction of EAC transport heading east and more heading south, with the mean separation latitude shifting >100 km southward. To examine the underlying dynamics, we remove New Zealand with two linear models: the Sverdrup/Godfrey Island Rule and NEMO in linear mode. We find that linear processes and deep bathymetry play a major role in the mean Tasman Front position, whereas nonlinear processes are crucial for the extent of the EAC retroflection. Contrary to past work, we find that meridional gradients in the basin-wide wind stress curl are not the sole factor determining the latitude of EAC separation. We suggest that the Tasman Front location is set by either the maximum meridional gradient in the wind stress curl or the northern tip of New Zealand, whichever is furthest north.
Crespo Gómes, Elizabeth Blanca; Sofia, Vito; Padilla, Sandra; Camargo, Mario; Zappia, Mario; Bartoloni, Alessandro; Nicoletti, Alessandra
2015-01-01
Objective we performed a three-stages door-to-door survey to estimate incidence and prevalence of epilepsy associated with convulsive seizures (EACS) in a rural area of Bolivia. Methods the study was carried out in the Cordillera Province, southern-eastern Bolivia. One hundred fourteen rural communities with a total population of 18,907 inhabitants were included in the survey. In order to identify subjects with EACS, trained fieldworkers administered a validated single screening question to the householders (stage I). A second face-to-face questionnaire was administered to each positive subject (stage II) that, in case of positive answer, underwent a complete neurological examination to confirm the diagnosis (stage III). We estimated age and sex specific life-time and active EACS prevalence at the prevalence day (30th June 2010). Incidence risk was evaluated for the 10-year period between January 2000 and December 2010. Results on prevalence day we identified 136 subjects with EACS, 124 of whom had active epilepsy. The life-time prevalence of EACS was 7.2/1,000 (7.6/1,000 age-adjusted to the world standard population) while the prevalence of active EACS was 6.6/1,000 (6.7/1,000 age-adjusted to the world standard population). Both life-time and active prevalence showed a peak (10.3/1,000) in the 15–24 years age group and, overall, were higher among women. During the incidence study period, 105 patients living in the study area had the onset of EACS. The crude incidence risk was 55.4/100,000 (49.5/100,000 age-adjusted to the world standard population). Incidence was slightly but not significantly higher among women (58.9/100,000 versus 51.9/100,000). Conclusions the present study demonstrated a considerable burden of EACS in the Bolivian Chaco, showing prevalence and incidence estimates close to those reported for low and middle- income countries and underlying the need of treatment programs. PMID:26427017
Bruno, Elisa; Quattrocchi, Graziella; Crespo Gómes, Elizabeth Blanca; Sofia, Vito; Padilla, Sandra; Camargo, Mario; Zappia, Mario; Bartoloni, Alessandro; Nicoletti, Alessandra
2015-01-01
we performed a three-stages door-to-door survey to estimate incidence and prevalence of epilepsy associated with convulsive seizures (EACS) in a rural area of Bolivia. the study was carried out in the Cordillera Province, southern-eastern Bolivia. One hundred fourteen rural communities with a total population of 18,907 inhabitants were included in the survey. In order to identify subjects with EACS, trained fieldworkers administered a validated single screening question to the householders (stage I). A second face-to-face questionnaire was administered to each positive subject (stage II) that, in case of positive answer, underwent a complete neurological examination to confirm the diagnosis (stage III). We estimated age and sex specific life-time and active EACS prevalence at the prevalence day (30th June 2010). Incidence risk was evaluated for the 10-year period between January 2000 and December 2010. on prevalence day we identified 136 subjects with EACS, 124 of whom had active epilepsy. The life-time prevalence of EACS was 7.2/1,000 (7.6/1,000 age-adjusted to the world standard population) while the prevalence of active EACS was 6.6/1,000 (6.7/1,000 age-adjusted to the world standard population). Both life-time and active prevalence showed a peak (10.3/1,000) in the 15-24 years age group and, overall, were higher among women. During the incidence study period, 105 patients living in the study area had the onset of EACS. The crude incidence risk was 55.4/100,000 (49.5/100,000 age-adjusted to the world standard population). Incidence was slightly but not significantly higher among women (58.9/100,000 versus 51.9/100,000). the present study demonstrated a considerable burden of EACS in the Bolivian Chaco, showing prevalence and incidence estimates close to those reported for low and middle- income countries and underlying the need of treatment programs.
Wang, Zhixiong; Cheng, Yulan; Abraham, John M; Yan, Rong; Liu, Xi; Chen, Wei; Ibrahim, Sariat; Schroth, Gary P; Ke, Xiquan; He, Yulong; Meltzer, Stephen J
2017-10-15
Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients. Genomic PCR and Sanger sequencing were performed to find the breakpoint of fusion genes. Five novel in-frame fusion transcripts were identified and verified in 40 EACs and in a validation cohort of 15 additional EACs (55 patients in all): fibroblast growth factor receptor 2 (FGFR2)-GRB2-associated binding protein 2 (GAB2) in 2 of 55 or 3.6%, Niemann-Pick C1 (NPC1)-maternal embryonic leucine zipper kinase (MELK) in 2 of 55 or 3.6%, ubiquitin-specific peptidase 54 (USP54)-calcium/calmodulin dependent protein kinase II γ (CAMK2G) in 2 of 55 or 3.6%, megakaryoblastic leukemia (translocation) 1 (MKL1)-fibulin 1 (FBLN1) in 1 of 55 or 1.8%, and CCR4-NOT transcription complex subunit 2 (CNOT2)-chromosome 12 open reading frame 49 (C12orf49) in 1 of 55 or 1.8%. A genomic analysis indicated that NPC1-MELK arose from a complex interchromosomal translocation event involving chromosomes 18, 3, and 9 with 3 rearrangement points, and this was consistent with chromoplexy. These data indicate that fusion transcripts occur at a stable frequency in EAC. Furthermore, our results indicate that chromoplexy is an underlying mechanism that generates fusion transcripts in EAC. These and other fusion transcripts merit further study as diagnostic markers and potential therapeutic targets in EAC. Cancer 2017;123:3916-24. © 2017 American Cancer Society. © 2017 American Cancer Society.
Derakhshan, Mohammad H; Arnold, Melina; Brewster, David H; Going, James J; Mitchell, David R; Forman, David; McColl, Kenneth E L
2016-02-01
The incidence of esophageal adenocarcinoma (EAC) is increasing while adenocarcinoma of the stomach is decreasing. We have investigated whether the incidences of these two cancers and their time trends might be inversely related pointing to a common environmental factor exerting opposite effects on these cancers. For cross-sectional analyses data were abstracted from "Cancer Incidence in Five Continents" (CI5) Volume X and GLOBOCAN 2012. Relevant ICD-10 codes were used to locate esophageal and gastric cancers anatomically, and ICD-O codes for the histological diagnosis of EAC. For longitudinal analyses, age standardized rates (ASRs) of EAC and total gastric cancer (TGC) were extracted from CI5C-Plus. Estimated (2012) ASRs were available for 51 countries and these showed significant negative correlations between EAC and both TGC (males: correlation coefficient (CC)=-0.38, P=0.006, females: CC=-0.41, P=0.003) and non-cardia gastric cancer rates (males: CC=-0.41, P=0.003 and females: CC=-0.43, P=0.005). Annual incidence trends were analyzed for 38 populations through 1989-2007 and showed significant decreases for TGC in 89% and increases for EAC in 66% of these, with no population showing a fall in the latter. Significant negative correlation between the incidence trends of the two cancers was observed in 27 of the 38 populations over the 19-50 years of available paired data. Super-imposition of the longitudinal and cross-sectional data indicated that populations with a current high incidence of EAC and low incidence of gastric cancer had previously resembled countries with a high incidence of gastric cancer and low incidence of EAC. The negative association between gastric cancer and EAC in both current incidences and time trends is consistent with a common environmental factor predisposing to one and protecting from the other.
Antitumor Effects of Palladium-α-Lipoic Acid Complex Formulation as an Adjunct in Radiotherapy.
Veena, Ravindran Kalathil; Ajith, Thekkuttuparambil Ananthanarayanan; Janardhanan, Kainoor Krishnankutty; Antonawich, Francis
2016-01-01
Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co. Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count. The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.
Alexandre, Leo; Clark, Allan B; Bhutta, Hina Y; Holt, Sean; Lewis, Michael P N; Hart, Andrew R
2014-03-01
Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population. We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications. In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39-0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92) (with high-dose use only). Statin use for 1-4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98). In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
2014-01-01
Background Physical activity has been inversely associated with risk of several cancers. We performed a systematic review and meta-analysis to evaluate the association between physical activity and risk of esophageal cancer (esophageal adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). Methods We conducted a comprehensive search of bibliographic databases and conference proceedings from inception through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Results The analysis included 9 studies (4 cohort, 5 case–control) reporting 1,871 cases of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that the risk of esophageal cancer was 29% lower among the most physically active compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89), with moderate heterogeneity (I2 = 47%). On histology-specific analysis, physical activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2 = 0%). There were only 3 studies reporting the association between physical activity and risk of ESCC with conflicting results, and the meta-analysis demonstrated a null association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across study design, geographic location and study quality, with a non-significant trend towards a dose–response relationship. Conclusions Meta-analysis of published observational studies indicates that physical activity may be associated with reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of EAC. PMID:24886123
Habib, M Rowshahul; Karim, M Rezaul
2011-10-01
To investigate experimentally the possible antitumor effect of methanol extract (ME) of Calotropis gigantea L. (C. gigantean) root bark and its petroleum ether (PEF) and chloroform (CF) soluble fractions against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. The effects of ME (10 and 20 mg/kg), PEF (40 and 80 mg/kg) and CF (20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied. Hematological profile and biochemical parameters (SALP, SGPT and SGOT) were also estimated. Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one. The life span of ME and CF treated animals was significantly (P<0.05) increased by 43.90% (20 mg ME/kg) and 57.07% (40 mg CF/kg). ME and CF brought back the hematological parameter more or less normal level. ME and CF also restored the altered levels of serum alkaline phosphatase (SALP) and serum glutamate oxaloacetate transaminase (SGOT). Methanol extract (ME) of C. gigantea root bark and its chloroform soluble fraction (CF) possesses significant antitumor activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
Zhao, Xia; Liu, Quanhong; Tang, Wei; Wang, Xiaobing; Wang, Pan; Gong, Liyan; Wang, Yuan
2009-01-01
In this study, we report evidence of the damage effects of sonodynamic therapy (SDT) on a novel intracellular target, cytoskeletal F-actin, that has great importance for cancer treatment. Ehrlich ascites carcinoma (EAC) cells suspended in PBS were exposed to ultrasound at 1.34 MHz for up to 60s in the presence and absence of protoporphyrin IX (PPIX). To evaluate the polymeric state and distribution of actin filaments (AF) we employed FITC-Phalloidin staining. The percentage of cells with intact AF was decreased with 10-80 microM PPIX after ultrasonic exposure, while only few cells with disturbed F-actin were observed with 80 microM PPIX alone. The fluorescence intensity of FITC-Phalloidin labeled cells was detected by flow cytometry. The morphological changes of EAC cells were observed by scanning electron microscope (SEM). The nuclei were stained with Hoechst 33258 to determine apoptosis. Cytoskeletal F-actin and cell morphological changes were dependent on the time after SDT. Some cells suffered deformations of plasma membrane as blebs that reacted positively to FITC-Phalloidin at 2h after SDT treatment. Many of the cells showed the typically apoptotic chromatin fragmentation. The alterations were more significant 4h later. Our results showed that cytoskeletal F-actin might represent an important target for the SDT treatment and the observed effect on F-actin and the subsequent bleb formation mainly due to apoptosis formation due to the treatment.
El-Serag, Hashem B; Naik, Aanand D; Duan, Zhigang; Shakhatreh, Mohammad; Helm, Ashley; Pathak, Amita; Hinojosa-Lindsey, Marilyn; Hou, Jason; Nguyen, Theresa; Chen, John; Kramer, Jennifer R
2016-08-01
The effectiveness of surveillance endoscopy in patients with Barrett's oesophagus (BE) for reducing oesophageal adenocarcinoma (EAC)-related mortality in patients with BE is unclear. This is a cohort study of patients with BE diagnosed in the National Veterans Affairs hospitals during 2004-2009 excluding those with conditions that affect overall survival. We identified those diagnosed with EAC after BE diagnosis through 2011 and conducted chart reviews to identify BE surveillance programme, and indication for EAC diagnosis, verify diagnosis, stage, therapy and cause of death. We examined the association between surveillance indication for EAC diagnosis with or without surveillance programme and EAC stage and treatment receipt in logistic regression models, and with time to death or cancer-related death using a Cox proportional hazards regression model. Among 29 536 patients with BE, 424 patients developed EAC during a mean follow-up of 5.0 years. A total of 209 (49.3%) patients with EAC were in BE surveillance programme and were diagnosed as a result of surveillance endoscopy. These patients were more likely to be diagnosed at an early stage (stage 0 or 1: 74.7% vs 56.2, p<0.001), survived longer (median 3.2 vs 2.3 years; p<0.001) and have lower cancer-related mortality (34.0% vs 54.0%, p<0.0001) and had a trend to receive oesophagectomy (51.2% vs 42.3%; p=0.07) than 215 patients diagnosed by non-BE surveillance endoscopy (17.2% of whom were BE surveillance failure). BE surveillance endoscopy was associated with a decreased risk of cancer-related death (HR 0.47, 0.35 to 0.64), which was largely explained by the early stage of EAC at the time of diagnosis. Similarly, the adjusted mortality for patients with cancer in a prior surveillance programme for overall death was 0.63 (0.47 to 0.84) compared with patients with cancer not in a surveillance programme. Surveillance endoscopy among patients with BE is associated with significantly better EAC outcomes including cancer-related mortality compared with other non-surveillance endoscopy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Outcomes of T1b esophageal adenocarcinoma patients.
Tian, Jianmin; Prasad, Ganapathy A; Lutzke, Lori S; Lewis, Jason T; Wang, Kenneth K
2011-12-01
Esophagectomy is usually recommended for patients with submucosal esophageal adenocarcinoma (T1b EAC) because of the potential for lymph node metastasis (LNM). Endoscopic management often differs based on the risk of metastasis. There is limited information on the difference in outcomes for T1b-EAC with and without esophagectomy. To investigate (1) the outcomes of T1b EAC treatments with and without esophagectomy and (2) the percentage of LNM at esophagectomy for T1b-EAC. Retrospective cohort. A tertiary Barrett's esophagus unit. Sixty-eight T1b EAC patients based on EMR histology. Esophagectomy and endoscopic therapies. Survival duration and mortality rate. A total of 68 patients had T1b EAC; cumulative mortality rate was 30.9% and median survival duration was 39.5 months. Thirty-nine underwent esophagectomy and 29 did not. Among patients who underwent esophagectomy, 13 (33.3%) had LNM, and the mortality rate was 50.0% and 11.1% for those with and without LNM, respectively (P < .01). For those with and without esophagectomy, the cumulative mortality rates were 25.6% and 37.9%, and median survival duration was 48.9 and 34.8 months, respectively. There was no statistical difference in Charlson comorbidity index, number of EMRs, mortality rate, or survival duration. In Cox proportional hazard model analysis, the hazard ratio for esophagectomy was 0.5 (P = .21). Retrospective, nonrandomized small sample size cohort. Among the patients with T1b EAC found in EMR specimens who underwent esophagectomy, one third had regional LNM. In our small series, patients who underwent esophagectomy did not have a significantly different survival duration from that of those who did not, indicating that these patients may have similar outcomes [corrected]. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.
Critchley-Thorne, Rebecca J; Davison, Jon M; Prichard, Jeffrey W; Reese, Lia M; Zhang, Yi; Repa, Kathleen; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory G; DeMarshall, Maureen; Foxwell, Tyler; Jobe, Blair A; Zaidi, Ali H; Duits, Lucas C; Bergman, Jacques J G H M; Rustgi, Anil; Falk, Gary W
2017-02-01
There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis. A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR. ©2016 American Association for Cancer Research.
The formation of a cold-core eddy in the East Australian Current
NASA Astrophysics Data System (ADS)
Macdonald, H. S.; Roughan, M.; Baird, M. E.; Wilkin, J.
2016-02-01
Cold-core eddies (CCEs) frequently form in western boundary currents and can affect continental shelf processes. It is not always clear, however, if baroclinic or barotropic instabilities contribute more to their formation. The Regional Ocean Modelling System (ROMS) is used to investigate the ocean state during the formation of a CCE in the East Australian Current (EAC) during October 2009. The observed eddy initially appeared as a small billow (approx. 50 km in length) that perturbed the landward edge of the EAC. The billow grew into a mesoscale CCE (approx. 100 km in diameter), diverting the EAC around it. A ROMS simulation with a realistic wind field reproduced a similar eddy. This eddy formed from negative vorticity waters found on the continental shelf south of the EAC separation point. A sensitivity analysis is performed whereby the impact of 3 different wind forcing scenarios, upwelling, downwelling, and no winds, are investigated. A CCE formed in all wind scenarios despite the wind induced changes in hydrographic conditions in the continental shelf and slope waters. As such, the source of energy for eddy formation did not come from the interactions of wind with the continental shelf waters. Analysis of strain and energy transformation confirms this by showing that the prevailing source of CCE energy was kinetic energy of the offshore EAC. These results clearly link the formation of the CCE to the swift flowing EAC and barotropic instabilities.
Effects of refluxate pH values on duodenogastroesophageal reflux-induced esophageal adenocarcinoma
Cheng, Peng; Li, Jian-Sheng; Gong, Jun; Zhang, Lian-Feng; Chen, Rong-Zhong
2011-01-01
AIM: To determine the effects of duodenogastric juice pH on the development of esophageal adenocarcinoma (EAC). METHODS: An animal model of duodenogastroesophageal reflux was established using Sprague-Dawley (SD) rats undergoing esophagoduodenostomy (ED). The development of EAC was investigated in rats exposed to duodenogastric juice of different pH. The rats were divided into three groups: low-pH group (group A), high-pH group (group B) and a sham-operated group as a control (group C) (n = 30 rats in each group). The incidence of esophagitis, Barrett’s esophagus (BE), intestinal metaplasia with dysplasia and EAC was observed 40 wk after the treatment. RESULTS: The incidence rate of esophagitis, BE, intestinal metaplasia with dysplasia and EAC was higher in groups A and B compared with the control group after 40 wk (P < 0.01), being 96% and 100% (P > 0.05), 88% and 82.4% (P > 0.05), 20% and 52.1% (P < 0.05), and 8% and 39% (P < 0.05), respectively. CONCLUSION: Non-acidic refluxate increases the occurrence of intestinal metaplasia with dysplasia and EAC while the low-pH gastric juice exerts a protective effect in the presence of duodenal juice. The non-acid reflux is particularly important in the progression from BE to cancer. Therefore, control of duodenal reflux may be an important prophylaxis for EAC. PMID:21799654
Thirdborough, Steve; Mellows, Toby; Garcia, Edwin; Woo, Jeongmin; Tod, Joanne; Frampton, Steve; Jenei, Veronika; Moutasim, Karwan A.; Kabir, Tasnuva D.; Brennan, Peter A; Venturi, Giulia; Ford, Kirsty; Herranz, Nicolas; Lim, Kue Peng; Clarke, James; Lambert, Daniel W.; Prime, Stephen S.; Underwood, Timothy J.; Vijayanand, Pandurangan; Eliceiri, Kevin W.; Woelk, Christopher; King, Emma V.; Gil, Jesus; Ottensmeier, Christian H.; Thomas, Gareth J.
2017-01-01
Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes. PMID:27992856
Mellone, Massimiliano; Hanley, Christopher J; Thirdborough, Steve; Mellows, Toby; Garcia, Edwin; Woo, Jeongmin; Tod, Joanne; Frampton, Steve; Jenei, Veronika; Moutasim, Karwan A; Kabir, Tasnuva D; Brennan, Peter A; Venturi, Giulia; Ford, Kirsty; Herranz, Nicolas; Lim, Kue Peng; Clarke, James; Lambert, Daniel W; Prime, Stephen S; Underwood, Timothy J; Vijayanand, Pandurangan; Eliceiri, Kevin W; Woelk, Christopher; King, Emma V; Gil, Jesus; Ottensmeier, Christian H; Thomas, Gareth J
2016-12-15
Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo , showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro , we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes.
Auricular Split-Thickness Skin Graft for Ear Canal Coverage.
Haidar, Yarah M; Walia, Sartaaj; Sahyouni, Ronald; Ghavami, Yaser; Lin, Harrison W; Djalilian, Hamid R
2016-12-01
Split-thickness skin graft (STSG) continues to be the preferred means of external auditory canal (EAC) reconstruction. We thus sought to describe our experience using skin from the posterior aspect of the auricle (SPAA) as a donor site in EAC reconstruction. Grafts were, on average, 5 × 10 mm in size and obtained with a No. 10 blade after tumescence injection. The cases of 39 patients who underwent 41 procedures were retrospectively reviewed. Of the 38 patients with both 3- and 6-month follow-ups, no postoperative stenosis or bony exposure occurred. STSG from the SPAA can be a good option in EAC reconstruction. Total EAC/tympanic membrane coverage can be obtained with STSG from the SPAA. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.
NASA Astrophysics Data System (ADS)
Ashida, Yugo; Daigo, Yuzo; Sugahara, Katsuo
2017-08-01
Commercial metals and alloys like carbon steels, stainless steels, and nickel-based super alloys frequently encounter the problem of environmentally assisted cracking (EAC) and resulting failure in engineering components. This article aims to provide a perspective on three critical industrial applications having EAC issues: (1) corrosion and cracking of carbon steels in automotive applications, (2) EAC of iron- and nickel-based alloys in salt production and processing, and (3) EAC of iron- and nickel-based alloys in supercritical water. The review focuses on current industrial-level understanding with respect to corrosion fatigue, hydrogen-assisted cracking, or stress corrosion cracking, as well as the dominant factors affecting crack initiation and propagation. Furthermore, some ongoing industrial studies and directions of future research are also discussed.
The School of Hard Knocks: The Development of Close Air Support in Burma during the Second World War
2015-05-23
Group CAOC Combined Air Operations Center CAS Close Air Support CBI China-Burma-India EAC Eastern Air Command FM Field Manual JP Joint...Command ( EAC ) solved problems identified by the American Volunteer Group (AVG) in 1942. EAC’s doctrine, procedures, and techniques laid the foundation for...named the Eastern Air Command ( EAC ), and oversaw the air-land cooperation during the Allied counter-offensive into Burma throughout 1943 and 1944.8 The
Vicari, Enzo; La Vignera, Sandro; Condorelli, Rosita; Calogero, Aldo Eugenio
2010-03-01
The lack of phosphodiesterase type 5 inhibitor effects in patients with erectile dysfunction (ED) of arterial origin may be caused by an endothelial dysfunction that causes a series of biochemical alterations leading to a reduced nitric oxide (NO) bioavailability and increased oxidative stress. The aim of this study was to evaluate the effects of the treatment with endothelial antioxidant compounds (EAC) on the erectile response to sildenafil in patients with arterial ED already treated with sildenafil (100 mg twice a week for 8 weeks). A patient was considered responsive when the 5-item International Index of Erectile Function questionnaire score increased by >5 points. Fifty-three patients with arterial ED, hypertension, and diabetes mellitus were randomly given, for 8 weeks, EAC (1 dose/day) and, after a wash out of 8 weeks, sildenafil (100 mg) plus EAC. The patients were divided into the following four groups: A (N = 12): patients with ED alone; B (N = 14): patients with ED plus atheromasic plaques and/or increased intima-media thickness of common carotid arteries; C (N = 14): patients with ED plus lower limb artery abnormalities; and D (N = 13): patients with ED plus carotid and lower limb artery abnormalities. The administration of EAC plus sildenafil resulted in a significantly higher number of responsive patients (N = 36, 68%) compared with sildenafil alone (N = 24, 45%) or EAC alone (N = 17, 32%). The percentage of patients who successfully responded to the combined treatment increased in the various groups. It was 83%, 64%, 71%, and 54%, respectively, for groups A, B, C, and D. Furthermore, patients treated with EAC and sildenafil reached a successful response in a shorter length of time (3 weeks) compared with patients responsive to sildenafil (5.2 weeks) or EAC (5.7 weeks) alone. EAC administration to patients with arterial ED improved the success rate to sildenafil. These data suggest that, in such patients, a combined treatment may be considered to increase bioavailable NO and to neutralize radical oxygen species, which in turn inactive NO.
New pyrazolopyridine analogs: Synthesis, antimicrobial, antiquorum-sensing and antitumor screening.
El-Gohary, N S; Shaaban, M I
2018-05-25
New pyrazolopyridine analogs were prepared and tested for antimicrobial efficacy toward Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Aspergillus fumigatus and Aspergillus flavus. Results revealed that compound 6 has prominent and broad spectrum antimicrobial activity. Compound 8 showed good antibacterial efficacy over the four tested bacterial strains. In addition, compounds 2-4 displayed interesting efficacy over S. aureus, B. cereus and P. aeruginosa as well as moderate efficacy toward E. coli, C. albicans, A. fumigatus and A. flavus. Furthermore, compounds 9 and 10 exhibited interesting efficacy over P. aeruginosa. Antiquorum-sensing efficacy of the same analogs toward Chromobacterium violaceum was also examined, whereas compounds 3, 4 and 6 displayed acceptable activity. In vitro antitumor assay of the new pyrazolopyridines toward liver (HepG2), breast (MCF-7) and cervix (Hela) cancer cells illustrated that compounds 2 and 5 have the highest antitumor activity over the three cell lines. Moreover, compound 4 exhibited interesting efficacy on all tested cell lines, whereas compound 7 showed good activity on MCF-7 cells. The most active in vitro antitumor analogs, 2, 4, 5 and 7 were assessed for in vivo antitumor efficacy on Ehrlich ascites carcinoma (EAC) cells, whereas compound 5 displayed the highest efficacy. In addition, cytotoxicity testing toward W138 and WISH normal cells revealed that all tested analogs are less cytotoxic than doxorubicin. The new analogs were evaluated for DNA-binding affinity, whereas compounds 2, 4 and 5 displayed the highest affinity. In silico studies concluded that all the new pyrazolopyridines are foreseen to have excellent oral absorption. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Barrett’s esophagus in 2016: From pathophysiology to treatment
Martinucci, Irene; de Bortoli, Nicola; Russo, Salvatore; Bertani, Lorenzo; Furnari, Manuele; Mokrowiecka, Anna; Malecka-Panas, Ewa; Savarino, Vincenzo; Savarino, Edoardo; Marchi, Santino
2016-01-01
Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett’s esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE. PMID:27158534
Kaz, Andrew M; Wong, Chao-Jen; Varadan, Vinay; Willis, Joseph E; Chak, Amitabh; Grady, William M
2016-01-01
The risk of developing Barrett's esophagus (BE) and/or esophageal adenocarcinoma (EAC) is associated with specific demographic and behavioral factors, including gender, obesity/elevated body mass index (BMI), and tobacco use. Alterations in DNA methylation, an epigenetic modification that can affect gene expression and that can be influenced by environmental factors, is frequently present in both BE and EAC and is believed to play a role in the formation of BE and its progression to EAC. It is currently unknown whether obesity or tobacco smoking influences the risk of developing BE/EAC via the induction of alterations in DNA methylation. To investigate this possibility, we assessed the genome-wide methylation status of 81 esophageal tissues, including BE, dysplastic BE, and EAC epithelia using HumanMethylation450 BeadChips (Illumina). We found numerous differentially methylated loci in the esophagus tissues when comparing males to females, obese to lean individuals, and smokers to nonsmokers. Differences in DNA methylation between these groups were seen in a variety of functional genomic regions and both within and outside of CpG islands. Several cancer-related pathways were found to have differentially methylated genes between these comparison groups. Our findings suggest obesity and tobacco smoking may influence DNA methylation in the esophagus and raise the possibility that these risk factors affect the development of BE, dysplastic BE, and EAC through influencing the epigenetic status of specific loci that have a biologically plausible role in cancer formation.
Baker, Beth H.; Martinovic-Weigelt, Dalma; Ferrey, Mark L.; Barber, Larry B.; Writer, Jeffrey H.; Rosenberry, Donald O.; Kiesling, Richard L.; Lundy, James R.; Schoenfuss, Heiko L.
2014-01-01
Contaminants of emerging concern, particularly endocrine active compounds (EACs), have been identified as a threat to aquatic wildlife. However, little is known about the impact of EACs on lakes through groundwater from onsite wastewater treatment systems (OWTS). This study aims to identify specific contributions of OWTS to Sullivan Lake, Minnesota, USA. Lake hydrology, water chemistry, caged bluegill sunfish (Lepomis macrochirus), and larval fathead minnow (Pimephales promelas) exposures were used to assess whether EACs entered the lake through OWTS inflow and the resultant biological impact on fish. Study areas included two OWTS-influenced near-shore sites with native bluegill spawning habitats and two in-lake control sites without nearby EAC sources. Caged bluegill sunfish were analyzed for plasma vitellogenin concentrations, organosomatic indices, and histological pathologies. Surface and porewater was collected from each site and analyzed for EACs. Porewater was also collected for laboratory exposure of larval fathead minnow, before analysis of predator escape performance and gene expression profiles. Chemical analysis showed EACs present at low concentrations at each study site, whereas discrete variations were reported between sites and between summer and fall samplings. Body condition index and liver vacuolization of sunfish were found to differ among study sites as did gene expression in exposed larval fathead minnows. Interestingly, biological exposure data and water chemistry did not match. Therefore, although results highlight the potential impacts of seepage from OWTS, further investigation of mixture effects and life history factor as well as chemical fate is warranted.
Dy, Alexander Edward S; Lapeña, José Florencio F
2018-04-01
To investigate associations between age, external auditory canal (EAC) dimensions, and cerumen retention/impaction among persons with Down syndrome (DS). This cross-sectional study evaluated EAC dimensions, cerumen retention/impaction, and middle ear status with pneumatoscopy after extraction in 130 persons with DS. Descriptive and inferential statistics correlated age, presence of impacted/retained cerumen, and EAC diameter. Of 260 ears in 67 males and 63 females with average age of 9.48 years, 72.3% (188) had EAC of ≤4 mm. Those ≤1 year were 4.97 times more likely to have cerumen problems than those >1 year (95% CI, 1.45-17.02, P = .011). The odds of having cerumen problems with an EAC diameter of ≤4 mm were 3.31 times higher than with a diameter of 5 mm (95% CI, 1.46-7.50, P = .004), and odds of having cerumen impaction were as much as 6.19 times higher (95% CI, 2.38-16.08, P < .001). Male gender and low-lying external ear were also associated with increased odds of cerumen problems. There is a high prevalence of cerumen retention/impaction in persons with DS compared to the general Philippine population and a higher prevalence rate for EAC stenosis than elsewhere. A canal diameter of 4 mm and below and age 1 year or less are associated with a significantly higher likelihood of cerumen retention/impaction.
Novel modified steroid derivatives of androstanolone as chemotherapeutic anti-cancer agents.
El-Far, Mohamed; Elmegeed, Gamal A; Eskander, Emad F; Rady, Hanaa M; Tantawy, Mohamed A
2009-10-01
The aim of the present study is to synthesize and evaluate new potential chemotherapeutic anti-tumor agents. Several thiazolo-, pyrido-, pyrano- and lactam steroid derivatives were obtained using 17beta-hydroxy-5alpha-androstan-3-one (androstanolone) 1 as starting steroid. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most pure and structurally promising compounds 7a, 10a, 12b, 18 and 23 were evaluated as anti-tumor agents. The in vitro cytotoxic activity was evaluated against hepatoma cell lines using MTT assay. Also the in vivo anti-tumor activity was evaluated against Ehrlich ascites carcinoma (EAC). The results of the in vitro study showed that at incubation time 72h, in olive oil, compound 7a was the most effective cytotoxic compound with IC(50) of 30 microM, while the effects of compounds 18 and 23 were approximately similar with IC(50) of 37 microM and 35 microM respectively. While the tested compounds when dissolved in DMSO showed approximately the same IC(50) at both 48 and 72h incubation period, compound 23 was the most effective cytotoxic with IC(50) 42 microM at 48h and 40 microM at 72h. The results of the in vivo study showed that all the tested novel compounds at 25mg/kg were effective against EAC. Our novel steroid derivatives are promising candidates as anti-cancer agents, none of the mice treated with our novel derivatives showed any toxic symptoms, but they also completely inhibited tumor growth and retained the hemoglobin content, body weight, and WBCs near normal values and similar to what obtained for the standard drug 5-flurouracil.
Medhat, Dalia; Hussein, Jihan; El-Naggar, Mehrez E; Attia, Mohamed F; Anwar, Mona; Latif, Yasmine Abdel; Booles, Hoda F; Morsy, Safaa; Farrag, Abdel Razik; Khalil, Wagdy K B; El-Khayat, Zakaria
2017-07-01
Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
75 FR 22577 - Proposed Notice and Comment Policy Version 2.0
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-29
... current policy limits EAC's ability to address the rare situations that require swift action. The proposed... Proposed Notice and Comment Policy 2.0. EAC's current Notice and Comment Policy is to provide effective...
EAC: A program for the error analysis of STAGS results for plates
NASA Technical Reports Server (NTRS)
Sistla, Rajaram; Thurston, Gaylen A.; Bains, Nancy Jane C.
1989-01-01
A computer code is now available for estimating the error in results from the STAGS finite element code for a shell unit consisting of a rectangular orthotropic plate. This memorandum contains basic information about the computer code EAC (Error Analysis and Correction) and describes the connection between the input data for the STAGS shell units and the input data necessary to run the error analysis code. The STAGS code returns a set of nodal displacements and a discrete set of stress resultants; the EAC code returns a continuous solution for displacements and stress resultants. The continuous solution is defined by a set of generalized coordinates computed in EAC. The theory and the assumptions that determine the continuous solution are also outlined in this memorandum. An example of application of the code is presented and instructions on its usage on the Cyber and the VAX machines have been provided.
Epidermoid cyst of the external auditory canal in children: diagnosis and management.
Abdel-Aziz, Mosaad
2011-07-01
Epidermoid cyst of the external auditory canal (EAC) is rarely encountered in the clinical practice, but when it occurs, it may cause obstruction of the meatus that necessitates surgical excision. The aims of this study were to present 9 pediatric patients with epidermoid cysts of the EAC and to evaluate the outcome of the surgical technique that has been used in excision. Surgical removal of the cyst was carried out through a simple transmeatal approach, a medially based rectangular skin flap was elevated and the cyst was completely removed. No complications or recurrence have been reported. Epidermoid cyst should be listed in the differential diagnosis of EAC masses; it appears on computed tomography as a cystic mass in the outer cartilaginous part of EAC that is usually limited to the soft tissue with no bone erosion. It can be removed easily through simple transmeatal approach with high success rate and no morbidity.
Neurobiological Correlates of Coping through Emotional Approach
Master, Sarah L.; Amodio, David M.; Stanton, Annette L.; Yee, Cindy M.; Hilmert, Clayton J.; Taylor, Shelley E.
2008-01-01
This investigation considered possible health-related neurobiological processes associated with “emotional approach coping” (EAC), or intentional efforts to identify, process, and express emotions surrounding stressors. It was hypothesized that higher dispositional use of EAC strategies would be related to neural activity indicative of greater trait approach motivational orientation and to lower proinflammatory cytokine and cortisol responses to stress. To assess these relationships, 46 healthy participants completed a questionnaire assessing the two components of EAC (i.e., emotional processing and emotional expression), and their resting frontal cortical asymmetry was measured using electroencephalography (EEG). A subset (N = 22) of these participants’ levels of the soluble receptor for tumor necrosis factor-alpha (sTNFαRII), interleukin-6 (IL-6), and cortisol (all obtained from oral fluids) were also assessed before and after exposure to an acute laboratory stressor. Consistent with predictions, higher reported levels of emotional expression were significantly associated with greater relative left-sided frontal EEG asymmetry, indicative of greater trait approach motivation. Additionally, people who scored higher on EAC, particularly the emotional processing component, tended to show a less-pronounced TNF-α stress response. EAC was unrelated to levels of IL-6 and cortisol. Greater left-sided frontal EEG asymmetry was significantly related to lower baseline levels of IL-6 and to lower stress-related levels of sTNFαRII, and was marginally related to lower stress-related levels of IL-6. The findings suggest that the salubrious effects of EAC strategies for managing stress may be linked to an approach-oriented neurocognitive profile and to well-regulated proinflammatory cytokine responses to stress. PMID:18558470
Mintram, Kate S; Brown, A Ross; Maynard, Samuel K; Thorbek, Pernille; Tyler, Charles R
2018-02-01
Endocrine active chemicals (EACs) are widespread in freshwater environments and both laboratory and field based studies have shown reproductive effects in fish at environmentally relevant exposures. Environmental risk assessment (ERA) seeks to protect wildlife populations and prospective assessments rely on extrapolation from individual-level effects established for laboratory fish species to populations of wild fish using arbitrary safety factors. Population susceptibility to chemical effects, however, depends on exposure risk, physiological susceptibility, and population resilience, each of which can differ widely between fish species. Population models have significant potential to address these shortfalls and to include individual variability relating to life-history traits, demographic and density-dependent vital rates, and behaviors which arise from inter-organism and organism-environment interactions. Confidence in population models has recently resulted in the EU Commission stating that results derived from reliable models may be considered when assessing the relevance of adverse effects of EACs at the population level. This review critically assesses the potential risks posed by EACs for fish populations, considers the ecological factors influencing these risks and explores the benefits and challenges of applying population modeling (including individual-based modeling) in ERA for EACs in fish. We conclude that population modeling offers a way forward for incorporating greater environmental relevance in assessing the risks of EACs for fishes and for identifying key risk factors through sensitivity analysis. Individual-based models (IBMs) allow for the incorporation of physiological and behavioral endpoints relevant to EAC exposure effects, thus capturing both direct and indirect population-level effects.
78 FR 77443 - Electricity Advisory Committee
Federal Register 2010, 2011, 2012, 2013, 2014
2013-12-23
... DEPARTMENT OF ENERGY Electricity Advisory Committee AGENCY: Office of Electricity Delivery and... announces a meeting of the Electricity Advisory Committee (EAC). The Federal Advisory Committee Act (Pub. L... at: http://energy.gov/oe/services/electricity-advisory-committee-eac . FOR FURTHER INFORMATION...
75 FR 16088 - Proposed Information Quality Guidelines Policy
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-31
... ELECTION ASSISTANCE COMMISSION Proposed Information Quality Guidelines Policy AGENCY: U.S... Quality Guidelines Policy. SUMMARY: The U.S. Election Assistance Commission (EAC) seeks public comment on the Proposed Information Quality Guidelines policy. The policy outlines the EAC's directives and...
Sillo, Hiiti B; Masota, Nelson E; Kisoma, Sunday; Rago, Lembit; Mgoyela, Veronica; Kaale, Eliangiringa A
2018-01-01
Availability of correct and adequate information about medicines is an important aspect in ensuring rational use of medicines and hence facilitating safety and expected efficacy of medicines during therapy. Package inserts have proven to be a good source of information to the prescribers and patients whereby they have been useful in highlighting important information pertaining proper use and handling of the medicines. The present study was aimed at establishing the extent to which package inserts of medicines circulating on the markets of the East African Community (EAC) Partner States conform to medicines information requirements as established in the harmonized guidelines as well as national guidelines. A total of 99 package inserts from six (6) types of medicines namely Albendazole, Artemether/Lumefantrine (ALu), Ciprofloxacin, Paracetamol, Amoxicillin and Metronidazole were purposefully collected from three EAC Partner States: Kenya, Tanzania and Uganda. The medicines were selected based on their indications as first line treatments, high rates of utilization within the medicines supply system and their positions in treatment of diseases of public importance across EAC Partner States. The inserts were evaluated on the availability of information regarding fifteen (15) parameters as extracted from the EAC harmonized guidelines for registration of medicines. Moreover, comparisons were made between the percentage conformity of the branded versus generic products, markets from which the samples were collected, origin of the manufacturer and type of medicine. Majority (93.9-100%) of the medicines' package inserts highly conformed to the inclusion of the information regarding the description and composition of the medications, indications, dosage and methods of administration, warnings and precautions, contraindications and storage conditions. However, the information on handling and disposal, container package description, excipients used, clinical pharmacology of the medicines, and directions regarding overdose ranked the least in conformance with conformity ranging from 13.1-52.5%. The parameter with the lowest observed percentage conformity among the branded products scored 50% as compared to 10.8% among the generic products. Moreover, there was no significant difference (P<0.05) in the percentage conformity of the package inserts collected from each of the three Partner States as compared to the average from studied medicines. A generally good conformity was observed among medicines manufactured by European based manufacturers as compared to those based in Asia and EAC Partner States. In addition, PIs of Albendazole, Ciprofloxacin, Amoxicillin and Artemether/Lumefantrine did show overall high conformity across most of the product information requirements. Our study revealed the existence of a significant number of medicinal products circulating on the markets of EAC Partner States without necessary compliance with all product information requirements. We therefore recommend that NMRAs ensure thorough pre-market assessment of product information as well as strengthening their post marketing surveillance to ensure that medicines circulating on the market comply to medicines information requirements at all times. Emphasis should also be given to manufacturers on the importance of inclusion of appropriate and adequate product information for the safety of patients, including advocating for inclusion of patient-friendly and easy to understand medicines information.
External auditory canal stenosis due to the use of powdered boric acid.
Dündar, Riza; Soy, Fatih Kemal; Kulduk, Erkan; Muluk, Nuray Bayar; Cingi, Cemal
2014-09-01
Acquired stenosis of the external auditory canal (EAC) may occur because of chronic external otitis, recurrent chronic catarrhal otitis media associated with tympanic membrane perforation, chronic dermatitis, tumors, and trauma. Stenosis occurs generally at the one-third bone part of the external auditory canal. In this article, we present 3 cases of acquired EAC stenosis due to the previous powdered boric acid application. Besides the presentation of surgical intervetions in these cases, we want to notify the physicians not to use or carefully use powdered boric acid because of the complication of EAC stenosis.
Saturnino-Oliveira, Jeison; Santos, Daiana Do Carmo; Guimarães, Adriana Gibara; Santos Dias, Antônio; Tomaz, Marcelo Amorim; Monteiro-Machado, Marcos; Estevam, Charles Santos; Lucca Júnior, Waldecy De; Maria, Durvanei Augusto; Melo, Paulo A.; Araújo, Adriano Antunes de Souza; Santos, Márcio Roberto Viana; Almeida, Jackson Roberto Guedes da Silva; Oliveira, Rita de Cássia Meneses; Pereira de Oliveira, Aldeidia; Quintans Júnior, Lucindo José
2014-01-01
Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation. PMID:25136627
Chiarelli, Antonio M.; Maclin, Edward L.; Low, Kathy A.; Fantini, Sergio; Fabiani, Monica; Gratton, Gabriele
2017-01-01
Abstract. Near infrared (NIR) light has been widely used for measuring changes in hemoglobin concentration in the human brain (functional NIR spectroscopy, fNIRS). fNIRS is based on the differential measurement and estimation of absorption perturbations, which, in turn, are based on correctly estimating the absolute parameters of light propagation. To do so, it is essential to accurately characterize the baseline optical properties of tissue (absorption and reduced scattering coefficients). However, because of the diffusive properties of the medium, separate determination of absorption and scattering across the head is challenging. The effective attenuation coefficient (EAC), which is proportional to the geometric mean of absorption and reduced scattering coefficients, can be estimated in a simpler fashion by multidistance light decay measurements. EAC mapping could be of interest for the scientific community because of its absolute information content, and because light propagation is governed by the EAC for source–detector distances exceeding 1 cm, which sense depths extending beyond the scalp and skull layers. Here, we report an EAC mapping procedure that can be applied to standard fNIRS recordings, yielding topographic maps with 2- to 3-cm resolution. Application to human data indicates the importance of venous sinuses in determining regional EAC variations, a factor often overlooked. PMID:28466026
DOE Office of Scientific and Technical Information (OSTI.GOV)
James, L.A.
1997-02-01
Environmentally-assisted cracking (EAC) of low-alloy steels in high-temperature aqueous environments typical of those employed in light-water reactor (LWR) systems has been a subject of considerable interest since the pioneering work of Kondo et al demonstrated significantly higher fatigue crack propagation (FCP) rates in water than would be expected in an air environment under similar conditions. Here, environmentally-assisted cracking (EAC) of low-alloy steels in elevated temperature aqueous environments is readily observed in many laboratory experiments conducted in autoclaves, yet the observation of EAC in actual components operating in the same environments is quite rare. Mass transport of sulfides from the crackmore » enclave by diffusion and convection occurring in operating components provides one plausible explanation to this apparent paradox. Another contribution to EAC mitigation may also arise from the non-constant stress amplitudes typical for many operating components. This paper provides a demonstration of how a single tensile overload to 40% above a steady-state maximum fatigue stress can retard subsequent crack growth at the steady-state level for a sufficient period of time that diffusion mass transport can reduce the crack-tip sulfide concentration to a level below that necessary to sustain EAC.« less
Chiarelli, Antonio M; Maclin, Edward L; Low, Kathy A; Fantini, Sergio; Fabiani, Monica; Gratton, Gabriele
2017-04-01
Near infrared (NIR) light has been widely used for measuring changes in hemoglobin concentration in the human brain (functional NIR spectroscopy, fNIRS). fNIRS is based on the differential measurement and estimation of absorption perturbations, which, in turn, are based on correctly estimating the absolute parameters of light propagation. To do so, it is essential to accurately characterize the baseline optical properties of tissue (absorption and reduced scattering coefficients). However, because of the diffusive properties of the medium, separate determination of absorption and scattering across the head is challenging. The effective attenuation coefficient (EAC), which is proportional to the geometric mean of absorption and reduced scattering coefficients, can be estimated in a simpler fashion by multidistance light decay measurements. EAC mapping could be of interest for the scientific community because of its absolute information content, and because light propagation is governed by the EAC for source-detector distances exceeding 1 cm, which sense depths extending beyond the scalp and skull layers. Here, we report an EAC mapping procedure that can be applied to standard fNIRS recordings, yielding topographic maps with 2- to 3-cm resolution. Application to human data indicates the importance of venous sinuses in determining regional EAC variations, a factor often overlooked.
Rebamipide suppresses PolyI:C-stimulated cytokine production in human conjunctival epithelial cells.
Ueta, Mayumi; Sotozono, Chie; Yokoi, Norihiko; Kinoshita, Shigeru
2013-09-01
We previously documented that ocular surface epithelial cells could regulate ocular surface inflammation and suggested that, while Toll-like receptor 3 upregulates, EP3, one of the prostaglandin E2 receptors, downregulates ocular surface inflammation. Others reported that rebamipide, a gastroprotective drug, could not only increase the gastric mucus production, but also suppressed gastric mucosal inflammation and that it was dominantly distributed in mucosal tissues. The eyedrop form of rebamipide, approved in Japan for use in the treatment of dry eye diseases, upregulates mucin secretion and production, thereby suppressing superficial punctate keratopathy on the ocular surface of patients with this disease. In the current study, we investigated whether rebamipide has anti- inflammatory effects on the ocular surface. To examine the effects of rebamipide on polyI:C-induced cytokine expression by primary human conjunctival epithelial cells, we used enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction assay. We studied the effects of rebamipide on ocular surface inflammation in our murine experimental allergic conjunctivitis (EAC) model. Rebamipide could suppress polyI:C-induced cytokine production and the expression of mRNAs for CXCL10, CXCL11, RANTES, MCP-1, and IL-6 in human conjunctival epithelial cells. In our EAC model, the topical administration of rebamipide suppressed conjunctival allergic eosinophil infiltration. The topical application of rebamipide on the ocular surface might suppress ocular surface inflammation by suppressing the production of cytokines by ocular surface epithelial cells.
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-29
... deadlines, the current policy limits EAC's ability to address the rare situations that require swift action... Procedure No. 1: Procedures for Voting by Circulation Version 2.0. EAC's current Proposed Rule of Agency...
Alvi, Muhammad A; Liu, Xinxue; O’Donovan, Maria; Newton, Richard; Wernisch, Lorenz; Shannon, Nicholas B; Shariff, Kareem; di Pietro, Massimiliano; Bergman, Jacques J G H M; Ragunath, Krish; Fitzgerald, Rebecca C
2016-01-01
Purpose Endoscopic surveillance of Barrett’s esophagus (BE) is problematic because dysplasia/early-stage neoplasia are frequently invisible and likely to be missed due to sampling bias. Molecular abnormalities may be more diffuse than dysplasia. The aim was therefore to test whether DNA methylation; especially on imprinted and X-chromosome genes; is able to detect dysplasia/early-stage neoplasia. Experimental design 27K methylation arrays were used to find genes best able to differentiate between 22 BE and 24 esophageal adenocarcinoma (EAC) samples. These were validated using pyrosequencing on a retrospective cohort (60 BE, 36 dysplastic and 90 EAC) and then in a prospective multicenter study (98 BE patients, including 28 dysplastic and 9 early EAC) designed to utilize biomarkers to stratify patients according to their prevalent dysplasia/EAC status. Results 23% genes on the array, including 7% of X-linked and 69% of imprinted genes, demonstrated statistically significant changes in methylation in EAC vs. BE (Wilcoxon P<0.05). 6/7 selected candidate genes were successfully internally (Pearson’s P<0.01) and externally validated (ANOVA P<0.001). Four genes (SLC22A18, PIGR, GJA12 and RIN2) showed the greatest area under curve (0.988) to distinguish between BE and dysplasia/EAC in the retrospective cohort. This methylation panel was able to stratify patients from the prospective cohort into three risk groups based on the number of genes methylated (low risk: <2 genes, intermediate: 2 and high: >2). Conclusion Widespread DNA methylation changes were observed in Barrett’s carcinogenesis including ≈70% of known imprinted genes. A four-gene methylation panel stratified BE patients into three risk groups with potential clinical utility. PMID:23243219
Cost-Effectiveness of Chemoprevention with Proton Pump Inhibitors in Barrett’s Esophagus
Freedberg, Daniel E.; Abrams, Julian A.; Wang, Y. Claire
2015-01-01
Background Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus. PPIs are prescribed for virtually all patients with Barrett’s esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated. Aim The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett’s esophagus without reflux. Methods We designed a state-transition Markov micro-simulation model of a hypothetical cohort of 50-year-old white men with Barrett’s esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios. Results Assuming 50 % reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19 %. Conclusions Chemoprevention with PPIs in patients with Barrett’s esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19 %. The identification of subgroups of Barrett’s esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma. PMID:24795040
Carcinoma of the middle ear and external auditory canal
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hahn, S.S.; Kim, J.A.; Goodchild, N.
1983-07-01
Thirty-one patients with malignant tumors of the middle ear and external auditory canal (EAC) were observed at the University of Virginia Hospital from 1956 through 1980. Of 27 patients with carcinoma, 21 had squamous cell carcinoma, 4 had basal cell carcinoma and 2 had adenoid cystic carcinoma. The 27 patients with carcinoma are reviewed with regard to clinical presentation, treatment modality, results and complications. The majority (67%) of patients had a history of chronic ear drainage, 22% had a previous mastoidectomy or polypectomy and 7% had an associated cholesteatoma. Eighty percent of patients with carcinoma limited to EAC were alivemore » and well at 5 years, compared to 43% of patients with involvement of the middle ear. Fifty-six percent of patients without invasion of the petrous bone were alive at 5 years compared to only 20% of patients with petrous bone involvement. The data strongly suggest that survival depends on the extent of disease. The corrected disease free 5 year survival rates were 14% for patients who had surgery alone and 50% for those who had surgery and radiotherapy. Of the three patients with advanced disease who received radiotherapy alone, none survived five years.« less
Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma
Rubenstein, Joel H.; Shaheen, Nicholas J.
2015-01-01
Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence in Western cultures. Barrett’s esophagus (BE) is the presumed precursor lesion for this cancer. Several other risk factors for this cancer have been described, including chronic heartburn, tobacco use, Caucasian race, and obesity. Despite these known associations, most patients with EAC present with symptoms of dysphagia from late-stage tumors—only a small minority of patients are identified in screening and surveillance programs. Diagnostic analysis of EAC usually commences with upper endoscopy, followed by cross-sectional imaging. Endoscopic ultrasound is useful to assess local extent of disease as well as the involvement regional lymph nodes. T1a EAC may be treated endoscopically; some patients with T1b disease might also benefit from endoscopic therapy. Locally advanced disease is generally managed with esophagectomy, often accompanied by neoadjuvant chemoradiotherapy or chemotherapy. The prognosis is based on tumor stage: patients with T1a tumors have an excellent prognoses, whereas few patients with advanced disease have longterm survival. PMID:25957861
Risk of progression of Barrett's esophagus in patients with cirrhosis
Apfel, Tehilla; Lopez, Rocio; Sanaka, Madhusudhan R; Thota, Prashanthi N
2017-01-01
AIM To study Barrett’s esophagus (BE) in cirrhosis and assess progression to esophageal adenocarcinoma (EAC) compared to non-cirrhotic BE controls. METHODS Cirrhotic patients who were found to have endoscopic evidence of BE confirmed by the presence of intestinal metaplasia on histology from 1/1/2000 to 12/1/2015 at Cleveland Clinic were included. Cirrhotic patients were matched 1:4 to BE controls without cirrhosis. Age, gender, race, BE length, hiatal hernia size, Child-Pugh (CP) class and histological findings were recorded. Cases and controls without high-grade dysplasia (HGD)/EAC and who had follow-up endoscopies were studied for incidence of dysplasia/EAC and to assess progression rates. Univariable conditional logistic regression was done to assess differences in baseline characteristics between the two groups. RESULTS A total of 57 patients with cirrhosis and BE were matched with 228 controls (BE without cirrhosis). The prevalence of dysplasia in cirrhosis and controls were similar with 8.8% vs 12% with low grade dysplasia (LGD) and 12.3 % vs 19.7% with HGD or EAC (P = 0.1). In the incidence cohort of 44 patients with median follow-up time of 2.7 years [interquartile range 1.0, 4.8], there were 7 cases of LGD, 2 cases of HGD, and 2 cases of EAC. There were no differences in incidence rates of HGD/EAC in nondysplastic BE between cirrhotic cases and noncirrhotic controls (1.4 vs 1.1 per 100 person- years, P = 0.8). In LGD, cirrhotic patients were found to have higher rates of progression to HGD/EAC compared to control group though this did not reach statistical significance (13.7 vs 8.1 per 100 person- years, P = 0.51). A significant association was found between a higher CP class and neoplastic progression of BE in cirrhotic patients (HR =7.9, 95%CI: 2.0-30.9, P = 0.003). CONCLUSION Cirrhotics with worsening liver function are at increased risk of progression of BE. More frequent endoscopic surveillance might be warranted in such patients. PMID:28566888
NASA Astrophysics Data System (ADS)
Syahailatua, Augy; Roughan, Moninya; Suthers, Iain M.
2011-03-01
Ichthyoplankton assemblages were compared between regions dominated by the oligotrophic East Australian Current (EAC) and the inner-shelf waters off southeastern Australia, to determine if the early life history of fish was related to the separation of the EAC from the coast, producing different water masses as well as characteristic taxa. Samples were collected at the surface and in sub-surface waters, at 50 and 100 m isobath stations, during two summer research voyages in November 1998 and January 1999. On both voyages the study region was characterized by coastal and EAC waters in the north (˜31°S), and in the south by topographically induced upwelling (˜31°S), associated with narrowing of the continental shelf and separation of the EAC from the coast. Among the 111 families of larval fish, we observed distinctive assemblages of ichthyoplankton associated with the two different water masses. A greater abundance of the Carangidae, Labridae, Lutjanidae, Microcanthidae, Myctophidae and Scombridae was associated with the nutrient poor EAC water mass, while the Callionymidae, Clupeidae, Platycephalidae and Sillaginidae were mostly found in the cooler and/or fresher inner-shelf water mass. We assessed these patterns with opportunistic samples from an unusual, wind-driven upwelling event in the north (˜31°S) earlier in the November voyage. The relative abundance of these 10 characteristic families distinguished this wind-driven upwelling event from the subsequent relaxation and predominance of the EAC assemblage at this location just 6 d later. Distinctive and abundant families such as larval clupeids, relative to larval carangids, could be a useful marker of inner-shelf, EAC and mixed water masses in the absence of robust hydrographic data. This and related studies indicate contrast in early life histories of Sardinops sagax and Trachurus spp., which appear to spawn respectively in the inner-shelf and outer-shelf waters. The post-flexion stages of S. sagax predominate in the outer-shelf and Tasman Front, while post-flexion Trachurus spp. predominate in inner-shelf water masses.
Prolonged resuscitation of metabolic acidosis after trauma is associated with more complications.
Weinberg, Douglas S; Narayanan, Arvind S; Moore, Timothy A; Vallier, Heather A
2015-09-24
Optimal patterns for fluid management are controversial in the resuscitation of major trauma. Similarly, appropriate surgical timing is often unclear in orthopedic polytrauma. Early appropriate care (EAC) has recently been introduced as an objective model to determine readiness for surgery based on the resuscitation of metabolic acidosis. EAC is an objective treatment algorithm that recommends fracture fixation within 36 h when either lactate <4.0 mmol/L, pH ≥ 7.25, or base excess (BE) ≥-5.5 mmol/L. The aim of this study is to better characterize the relationship between post-operative complications and the time required for resuscitation of metabolic acidosis using EAC. At an adult level 1 trauma center, 332 patients with major trauma (Injury Severity Score (ISS) ≥16) were prospectively treated with EAC. The time from injury to EAC resuscitation was determined in all patients. Age, race, gender, ISS, American Society of Anesthesiologists score (ASA), body mass index (BMI), outside hospital transfer status, number of fractures, and the specific fractures were also reviewed. Complications in the 6-month post-operative period were adjudicated by an independent multidisciplinary committee of trauma physicians and included infection, sepsis, pulmonary embolism, deep venous thrombosis, renal failure, multiorgan failure, pneumonia, and acute respiratory distress syndrome. Univariate analysis and binomial logistic regression analysis were used to compare complications between groups. Sixty-six patients developed complications, which was less than a historical cohort of 1,441 patients (19.9% vs. 22.1%). ISS (p < 0.0005) and time to EAC resuscitation (p = 0.041) were independent predictors of complication rate. A 2.7-h increase in time to resuscitation had odds for sustaining a complication equivalent to a 1-unit increase on the ISS. EAC guidelines were safe, effective, and practically implemented in a level 1 trauma center. During the resuscitation course, increased exposure to acidosis was associated with a higher complication rate. Identifying the innate differences in the response, regulation, and resolution of acidosis in these critically injured patients is an important area for trauma research. Level 1: prognostic study.
1985-09-01
4 C/SCSC Terms and Definitions ...... ..... 5 Cost Performance Report Analysis (CPA) Progrra" m 6 Description of CPRA Terms and Formulas...hypotheses are: 1 2 C2: al’ 02 ’ The test statistic is then calculated as: F* (( SSEI + (nI - 2)) / (SSE 2 + (n 2 - 2))] The critical F value is: F(c, nl...353.90767 SIGNIF F = .0000 44 ,1 42 •.4 m . - .TABLE B.4 General Linear Test for EAC1 and EAC5 MEAN STD DEV CASES ECAC 827534.056 1202737.882 1630 EACS
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Wan-Yu; Kuo, Sung-Hsin; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
Purpose: To report outcomes of the rare disease of squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). Failure patterns related to spatial dose distribution were also analyzed to provide insight into target delineation. Methods and Materials: A retrospective review was conducted of the records of 11 consecutive patients with SCC of the EAC and middle ear who were treated with curative surgery and postoperative IMRT at one institution between January 2007 and February 2010. The prescribed IMRT dose was 60 to 66 Gy at 2 Gy permore » fraction. Three patients also received concurrent cisplatin-based chemotherapy, and 1 patient received concurrent oral tegafur/uracil. The median follow-up time was 19 months (range, 6-33 months). Results: Four patients had locoregional recurrence, yielding an estimated 2-year locoregional control rate of 70.7%. Among them, 1 patient had persistent disease after treatment, and 3 had marginal recurrence. Distant metastasis occurred in 1 patient after extensive locoregional recurrence, yielding an estimated 2-year distant control rate of 85.7%. The estimated 2-year overall survival was 67.5%. The three cases of marginal recurrence were near the preauricular space and glenoid fossa of the temporomandibular joint, adjacent to the apex of the ear canal and glenoid fossa of the temporomandibular joint, and in the postauricular subcutaneous area and ipsilateral parotid nodes, respectively. Conclusions: Marginal misses should be recognized to improve target delineation. When treating SCC of the EAC and middle ear, care should be taken to cover the glenoid fossa of the temporomandibular joint and periauricular soft tissue. Elective ipsilateral parotid irradiation should be considered. The treatment planning procedure should also be refined to balance subcutaneous soft-tissue dosimetry and toxicity.« less
Chen, Wan-Yu; Kuo, Sung-Hsin; Chen, Yu-Hsuan; Lu, Szu-Huai; Tsai, Chiao-Ling; Cheng, Jason Chia-Hsien; Hong, Ruey-Long; Chen, Ya-Fang; Hsu, Chuan-Jen; Lin, Kai-Nan; Ko, Jenq-Yuh; Lou, Pei-Jen; Wang, Cheng-Ping; Chong, Fok-Ching; Wang, Chun-Wei
2012-03-15
To report outcomes of the rare disease of squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). Failure patterns related to spatial dose distribution were also analyzed to provide insight into target delineation. A retrospective review was conducted of the records of 11 consecutive patients with SCC of the EAC and middle ear who were treated with curative surgery and postoperative IMRT at one institution between January 2007 and February 2010. The prescribed IMRT dose was 60 to 66 Gy at 2 Gy per fraction. Three patients also received concurrent cisplatin-based chemotherapy, and 1 patient received concurrent oral tegafur/uracil. The median follow-up time was 19 months (range, 6-33 months). Four patients had locoregional recurrence, yielding an estimated 2-year locoregional control rate of 70.7%. Among them, 1 patient had persistent disease after treatment, and 3 had marginal recurrence. Distant metastasis occurred in 1 patient after extensive locoregional recurrence, yielding an estimated 2-year distant control rate of 85.7%. The estimated 2-year overall survival was 67.5%. The three cases of marginal recurrence were near the preauricular space and glenoid fossa of the temporomandibular joint, adjacent to the apex of the ear canal and glenoid fossa of the temporomandibular joint, and in the postauricular subcutaneous area and ipsilateral parotid nodes, respectively. Marginal misses should be recognized to improve target delineation. When treating SCC of the EAC and middle ear, care should be taken to cover the glenoid fossa of the temporomandibular joint and periauricular soft tissue. Elective ipsilateral parotid irradiation should be considered. The treatment planning procedure should also be refined to balance subcutaneous soft-tissue dosimetry and toxicity. Copyright © 2012 Elsevier Inc. All rights reserved.
Socialist Consciousness Raising and Cuba's School to the Countryside Program
ERIC Educational Resources Information Center
Blum, Denise
2008-01-01
As a participant-observer, the author relates observations, interviews, and surveys from her experience in a Cuban Escuela al Campo ("School to the Countryside," or EAC) camp located on a collective farm outside of the city of Havana. The Pioneers, the youth section of the official Cuban Communist Party, organize the EAC program…
A Spanish Version of the Expectations about Counseling Questionnaire: Translation and Validation.
ERIC Educational Resources Information Center
Buhrke, Robin A.; Jorge, Michael
1992-01-01
Summarizes two studies conducted for the development and validation of a Spanish version of the Expectations about Counseling (EAC) questionnaire. Administered English and Spanish versions to bilingual university students and bilingual nonstudents. Results suggest that the Spanish version of the EAC is a reliable and valid translation for students…
76 FR 4880 - Privacy Act of 1974; Systems of Records
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Hydrogen interactions in aluminum-lithium alloys
NASA Technical Reports Server (NTRS)
Smith, S. W.; Scully, J. R.
1991-01-01
A program is described which seeks to develop an understanding of the effects of dissolved and trapped hydrogen on the mechanical properties of selected Al-Li-Cu-X alloys. A proposal is made to distinguish hydrogen (H2) induced EAC from aqueous dissolution controlled EAC, to correlate H2 induced EAC with mobile and trapped concentrations, and to identify significant trap sites and hydride phases (if any) through use of model alloys and phases. A literature review shows three experimental factors which have impeded progress in the area of H2 EAC for this class of alloys. These are as listed: (1) inter-subgranular fracture in Al-Li alloys when tested in the S-T orientation in air or vacuum make it difficult to readily detect H2 induced fracture based on straight forward changes in fractography; (2) the inherently low H2 diffusivity and solubility in Al alloys is further compounded by a native oxide which acts as a H2 permeation barrier; and (3) H2 effects are masked by dissolution assisted processes when mechanical testing is performed in aqueous solutions.
Ghetti, Claire M
2013-01-01
Individuals undergoing cardiac catheterization are likely to experience elevated anxiety periprocedurally, with highest anxiety levels occurring immediately prior to the procedure. Elevated anxiety has the potential to negatively impact these individuals psychologically and physiologically in ways that may influence the subsequent procedure. This study evaluated the use of music therapy, with a specific emphasis on emotional-approach coping, immediately prior to cardiac catheterization to impact periprocedural outcomes. The randomized, pretest/posttest control group design consisted of two experimental groups--the Music Therapy with Emotional-Approach Coping group [MT/EAC] (n = 13), and a talk-based Emotional-Approach Coping group (n = 14), compared with a standard care Control group (n = 10). MT/EAC led to improved positive affective states in adults awaiting elective cardiac catheterization, whereas a talk-based emphasis on emotional-approach coping or standard care did not. All groups demonstrated a significant overall decrease in negative affect. The MT/EAC group demonstrated a statistically significant, but not clinically significant, increase in systolic blood pressure most likely due to active engagement in music making. The MT/EAC group trended toward shortest procedure length and least amount of anxiolytic required during the procedure, while the EAC group trended toward least amount of analgesic required during the procedure, but these differences were not statistically significant. Actively engaging in a session of music therapy with an emphasis on emotional-approach coping can improve the well-being of adults awaiting cardiac catheterization procedures.
Rabeprazole- versus esomeprazole-based eradication regimens for H. pylori infection.
Wu, I-Chen; Wu, Deng-Chyang; Hsu, Ping-I; Lu, Chien-Yu; Yu, Fang-Jung; Wang, Tsang-En; Chang, Wen-Hsiung; Chen, Jyh-Jon; Kuo, Fu-Chen; Wu, Jeng-Yih; Wang, Wen-Ming; Bair, Ming-Jong
2007-12-01
Different kinds of proton pump inhibitor-based triple therapies could result in different Helicobacter pylori eradication rates. The aims of this study were to compare the efficacy and safety of rabeprazole- and esomeprazole-based triple therapy in primary treatment of H. pylori infection in Taiwan. From June 2005 to March 2007, 420 H. pylori-infected patients were randomly assigned to receive a 7-day eradication therapy with either esomeprazole 40 mg daily (EAC group, n = 209) or rabeprazole 20 mg b.i.d. (RAC group, n = 211) in combination with amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d.. Follow-up endoscopy with biopsy was done 12-16 weeks after completion of eradication therapy. Those who refused endoscopic exams underwent (13)C-urea breath test to assess the treatment response. Intention-to-treat analysis revealed that the eradication rate was 89.4% in the EAC group and 90.5% in RAC groups (p-value = .72). All of the subjects returned for assessment of compliance (100% in EAC group vs. 99.5% in RAC group, p-value = .32) and adverse events (3.83% in EAC group vs. 6.16% in RAC group, p-value = .27). Sixty (28.7%) and 37 (17.6%) patients in EAC and RAC group, respectively, refused endoscopy and underwent a (13)C-urea breath test to determine the treatment effect. In conclusion, rabeprazole- and esomeprazole-based primary therapies for H. pylori infection are comparable in efficacy and safety.
NASA Astrophysics Data System (ADS)
Kim, Tae Hyun
2017-05-01
The complexation behavior of diazophenylcalix[4]arene bearing para-ethylester group (p-EAC) for alkali, alkaline earth, various heavy and transition metal ions (Li+, Na+, K+, Rb+, Cs+, Mg2 +, Ca2 +, Sr2 +, Ba2 +, Cr3 +, Fe2 +, Co2 +, Ni2 +, Cu2 +, Zn2 +, Pb2 +) was investigated by spectrophotometric and electrochemical methods in CH3CN. p-EAC exhibits decreased absorbance at 353 nm in the presence of Cr3 +, Fe2 +, Pb2 +, and Cu2 +. The spectra of p-EAC showed bathochromic shift in absorption maximum on the addition of Cr3 +, Fe2 +, or Pb2 + with decreasing order of absorbance (Cr3 + > Fe2 + > Pb2 +), and on the other hand, hypsochromic shift on the addition of Cu2 +. This leads to the selective coloration from light green to orange and colorless for Cr3 + and Cu2 + that can be detected by the naked eye, respectively. In electrochemistry experiments, p-EAC also showed two different types of voltammetric changes toward Cr3 +, Fe2 +, or Pb2 +, and toward Cu2 +, whereas no significant changes occurred in the presence of the other metal ions. Nonlinear fitting curve procedure was used to determine a logarithmic value of 5.20, 4.92, 3.54 and 4.80 for the stability constants of the complex of p-EAC with Cr3 +, Fe2 +, Pb2 +, and Cu2 +, respectively.
High yield reproducible rat model recapitulating human Barrett’s carcinogenesis
Matsui, Daisuke; Omstead, Ashten N; Kosovec, Juliann E; Komatsu, Yoshihiro; Lloyd, Emily J; Raphael, Hailey; Kelly, Ronan J; Zaidi, Ali H; Jobe, Blair A
2017-01-01
AIM To efficiently replicate the biology and pathogenesis of human esophageal adenocarcinoma (EAC) using the modified Levrat model of end-to-side esophagojejunostomy. METHODS End-to-side esophagojejunostomy was performed on rats to induce gastroduodenoesophageal reflux to develop EAC. Animals were randomly selected and serially euthanized at 10 (n = 6), 17 (n = 8), 24 (n = 9), 31 (n = 6), 38 (n = 6), and 40 (n = 6) wk postoperatively. The esophagi were harvested for downstream histopathology and gene expression. Histological evaluation was completed to determine respective rates of carcinogenic development. Quantitative reverse transcription-polymerase chain reaction was performed to determine gene expression levels of MUC2, CK19, and CK20, and results were compared to determine significant differences throughout disease progression stages. RESULTS The overall study mortality was 15%. Causes of mortality included anastomotic leak, gastrointestinal hemorrhage, stomach ulcer perforation, respiratory infection secondary to aspiration, and obstruction due to tumor or late anastomotic stricture. 10 wk following surgery, 100% of animals presented with esophagitis. Barrett’s esophagus (BE) was first observed at 10 wk, and was present in 100% of animals by 17 wk. Dysplasia was confirmed in 87.5% of animals at 17 wk, and increased to 100% by 31 wk. EAC was first observed in 44.4% of animals at 24 wk and increased to 100% by 40 wk. In addition, two animals at 38-40 wk post-surgery had confirmed macro-metastases in the lung/liver and small intestine, respectively. MUC2 gene expression was progressively down-regulated from BE to dysplasia to EAC. Both CK19 and CK20 gene expression significantly increased in a stepwise manner from esophagitis to EAC. CONCLUSION Esophagojejunostomy was successfully replicated in rats with low mortality and a high tumor burden, which may facilitate broader adoption to study EAC development, progression, and therapeutics. PMID:28970723
Boo, Marie E; Garrison, J Craig; Hannon, Joseph P; Creed, Kalyssa M; Goto, Shiho; Grondin, Angellyn N; Bothwell, James M
2018-03-01
Female patients are more likely to suffer a second anterior cruciate ligament (ACL) injury after ACL reconstruction (ACLR) and return to sport (RTS) compared with healthy female controls. Few studies have examined the energy absorption contribution (EAC) that could lead to this subsequent injury. The ACLR group would demonstrate an altered EAC between joints (hip, knee, and ankle) but no difference in quadriceps, hip abduction, or hip external rotation (ER) strength at the time of RTS. Cross-sectional study; Level of evidence, 3. A total of 34 female participants (ACLR: n = 17; control: n = 17) were enrolled in the study and matched for age and activity level. Jump landing performance for the initial 50 milliseconds of landing of a lateral-vertical jump was assessed using a 10-camera 3-dimensional motion capture system and 2 force plates. Isokinetic quadriceps strength was measured using a Biodex machine, and hip abduction and ER isometric strength were measured using a handheld dynamometer. All values were normalized to the participant's height and weight. A 1-way multivariate analysis of variance was used to assess between-group differences in the EAC at the hip, knee, and ankle. Two 1-way analyses of variance were used to independently examine quadriceps, hip abduction, and hip ER strength between the groups. Significant differences in the EAC were found between the groups for the involved hip ( P = .002), uninvolved hip ( P = .005), and involved ankle ( P = .023). There were no between-group differences in the EAC for the involved or uninvolved knee or the uninvolved ankle. Patients who underwent ACLR demonstrated significantly decreased quadriceps strength on the involved limb ( P = .02) and decreased hip ER strength on both the involved ( P = .005) and uninvolved limbs ( P = .002). No significant strength differences were found between the groups for the uninvolved quadriceps or for involved or uninvolved hip abduction. At RTS, patients who underwent ACLR utilized a greater hip EAC bilaterally and a decreased involved ankle EAC during a lateral-vertical jump. Furthermore, quadriceps strength on the involved limb and hip ER strength of bilateral lower extremities remained decreased. This could place greater stress on the ACL graft and ultimately lead to an increased injury risk.
Boo, Marie E.; Garrison, J. Craig; Hannon, Joseph P.; Creed, Kalyssa M.; Goto, Shiho; Grondin, Angellyn N.; Bothwell, James M.
2018-01-01
Background: Female patients are more likely to suffer a second anterior cruciate ligament (ACL) injury after ACL reconstruction (ACLR) and return to sport (RTS) compared with healthy female controls. Few studies have examined the energy absorption contribution (EAC) that could lead to this subsequent injury. Hypothesis: The ACLR group would demonstrate an altered EAC between joints (hip, knee, and ankle) but no difference in quadriceps, hip abduction, or hip external rotation (ER) strength at the time of RTS. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 34 female participants (ACLR: n = 17; control: n = 17) were enrolled in the study and matched for age and activity level. Jump landing performance for the initial 50 milliseconds of landing of a lateral-vertical jump was assessed using a 10-camera 3-dimensional motion capture system and 2 force plates. Isokinetic quadriceps strength was measured using a Biodex machine, and hip abduction and ER isometric strength were measured using a handheld dynamometer. All values were normalized to the participant’s height and weight. A 1-way multivariate analysis of variance was used to assess between-group differences in the EAC at the hip, knee, and ankle. Two 1-way analyses of variance were used to independently examine quadriceps, hip abduction, and hip ER strength between the groups. Results: Significant differences in the EAC were found between the groups for the involved hip (P = .002), uninvolved hip (P = .005), and involved ankle (P = .023). There were no between-group differences in the EAC for the involved or uninvolved knee or the uninvolved ankle. Patients who underwent ACLR demonstrated significantly decreased quadriceps strength on the involved limb (P = .02) and decreased hip ER strength on both the involved (P = .005) and uninvolved limbs (P = .002). No significant strength differences were found between the groups for the uninvolved quadriceps or for involved or uninvolved hip abduction. Conclusion: At RTS, patients who underwent ACLR utilized a greater hip EAC bilaterally and a decreased involved ankle EAC during a lateral-vertical jump. Furthermore, quadriceps strength on the involved limb and hip ER strength of bilateral lower extremities remained decreased. This could place greater stress on the ACL graft and ultimately lead to an increased injury risk. PMID:29552573
Rinne test: does the tuning fork position affect the sound amplitude at the ear?
Butskiy, Oleksandr; Ng, Denny; Hodgson, Murray; Nunez, Desmond A
2016-03-24
Guidelines and text-book descriptions of the Rinne test advise orienting the tuning fork tines in parallel with the longitudinal axis of the external auditory canal (EAC), presumably to maximise the amplitude of the air conducted sound signal at the ear. Whether the orientation of the tuning fork tines affects the amplitude of the sound signal at the ear in clinical practice has not been previously reported. The present study had two goals: determine if (1) there is clinician variability in tuning fork placement when presenting the air-conduction stimulus during the Rinne test; (2) the orientation of the tuning fork tines, parallel versus perpendicular to the EAC, affects the sound amplitude at the ear. To assess the variability in performing the Rinne test, the Canadian Society of Otolaryngology - Head and Neck Surgery members were surveyed. The amplitudes of the sound delivered to the tympanic membrane with the activated tuning fork tines held in parallel, and perpendicular to, the longitudinal axis of the EAC were measured using a Knowles Electronics Mannequin for Acoustic Research (KEMAR) with the microphone of a sound level meter inserted in the pinna insert. 47.4 and 44.8% of 116 survey responders reported placing the fork parallel and perpendicular to the EAC respectively. The sound intensity (sound-pressure level) recorded at the tympanic membrane with the 512 Hz tuning fork tines in parallel with as opposed to perpendicular to the EAC was louder by 2.5 dB (95% CI: 1.35, 3.65 dB; p < 0.0001) for the fundamental frequency (512 Hz), and by 4.94 dB (95% CI: 3.10, 6.78 dB; p < 0.0001) and 3.70 dB (95% CI: 1.62, 5.78 dB; p = .001) for the two harmonic (non-fundamental) frequencies (1 and 3.15 kHz), respectively. The 256 Hz tuning fork in parallel with the EAC as opposed to perpendicular to was louder by 0.83 dB (95% CI: -0.26, 1.93 dB; p = 0.14) for the fundamental frequency (256 Hz), and by 4.28 dB (95% CI: 2.65, 5.90 dB; p < 0.001) and 1.93 dB (95% CI: 0.26, 3.61 dB; p = .02) for the two harmonic frequencies (500 and 4 kHz) respectively. Clinicians vary in their orientation of the tuning fork tines in relation to the EAC when performing the Rinne test. Placement of the tuning fork tines in parallel as opposed to perpendicular to the EAC results in a higher sound amplitude at the level of the tympanic membrane.
75 FR 22769 - Sunshine Act Notice
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Ab-Rahman, Mohammad Syuhaimi; Yusoff, Abdul Rahman Mohd; Abdul, Nasrul Amir; Hipni, Afiq
2015-01-01
Development of a robust platform is important to ensure that the engineering accreditation process can run smoothly, completely and the most important is to fulfill the criteria requirements. In case of Malaysia, the preparation for EAC (Engineering Accreditation Committee) assessment required a good strategic plan of academic management system…
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Gender difference in gastro-esophageal reflux diseases.
Asanuma, Kiyotaka; Iijima, Katsunori; Shimosegawa, Tooru
2016-02-07
The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.
Gender difference in gastro-esophageal reflux diseases
Asanuma, Kiyotaka; Iijima, Katsunori; Shimosegawa, Tooru
2016-01-01
The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett’s esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen. PMID:26855539
Hot Food and Beverage Consumption and the Risk of Esophageal Cancer: A Meta-Analysis.
Andrici, Juliana; Eslick, Guy D
2015-12-01
Esophageal cancer is a neoplasm with a poor prognosis. Its two histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have been associated with different risk factors. The possibility of an association between the consumption of hot food and beverages and esophageal cancer, especially ESCC, has long been suspected, presenting a potentially modifiable risk factor. A meta-analysis of existing observational studies was performed to provide a quantitative estimate of the risk of esophageal cancer associated with the consumption of hot food and drink. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to November 11, 2014. Pooled ORs and 95% CIs were calculated using a random effects model for the risk of esophageal cancer associated with the consumption of hot food and drink. Subgroup analyses were conducted for ESCC and EAC, as well as for studies that adjusted for tobacco smoking and alcohol consumption, two well-recognized risk factors for ESCC. Consumption of hot food and drink was associated with an increased risk of any esophageal cancer (OR=1.90, 95% CI=1.46, 2.48). Heterogeneity was observed. There was an increased risk of ESCC (OR=2.29, 95% CI=1.79, 2.93), which remained even after adjusting for significant confounding variables (OR=2.39, 95% CI=1.71, 3.33). The relationship was not significant for EAC. The consumption of hot food and beverages was associated with an increased risk of esophageal cancer, particularly ESCC. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.
Incidence and survival differences in esophageal cancer among ethnic groups in the United States
Chen, Zheling; Ren, Yinghong; Du, Xianglin L; Yang, Jiao; Shen, Yanwei; Li, Shuting; Wu, Yunying; Lv, Meng; Dong, Danfeng; Li, Enxiao; Li, Wei; Liu, Peijun; Yang, Jin; Yi, Min
2017-01-01
Objectives This study was performed to identify the differences in incidence, clinicopathological features, and survival in esophageal cancer among ethnic groups in the United States and to determine the reasons for the differences. Result A total of 49,766 patients were included. Black and Asian groups had a higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%, respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non-Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic groups declined since 1973, especially in black males. At the same time, incidences of esophageal adenocarcinoma (EAC) dramatically increased in white males since 1973. And incidences of ESCC and EAC were the lowest and stable in Asian female. Multivariable models showed that patients who were male, or black, or had larger tumors, or positive lymph nodes had an increased risk of death from esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated with surgery had a lower likelihood of death. For ESCC, the black patients had the lowest DSS, while for EAC there were no significant differences in DSS among the ethnic/racial groups. Materials and Method From the Surveillance, Epidemiology, and End Results Program database, patients diagnosed with esophageal cancer from 1998-2013 were identified. Differences in incidences, clinicopathological features, treatments, and disease-specific survival (DSS) in four broad racial/ethnic groups were compared. Conclusion Histological type distribution between racial groups could be an important consideration in the incidence and the survival trend but other factors could also have an effect. PMID:28410201
Incidence and survival differences in esophageal cancer among ethnic groups in the United States.
Chen, Zheling; Ren, Yinghong; Du, Xianglin L; Yang, Jiao; Shen, Yanwei; Li, Shuting; Wu, Yunying; Lv, Meng; Dong, Danfeng; Li, Enxiao; Li, Wei; Liu, Peijun; Yang, Jin; Yi, Min
2017-07-18
This study was performed to identify the differences in incidence, clinicopathological features, and survival in esophageal cancer among ethnic groups in the United States and to determine the reasons for the differences. A total of 49,766 patients were included. Black and Asian groups had a higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%, respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non-Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic groups declined since 1973, especially in black males. At the same time, incidences of esophageal adenocarcinoma (EAC) dramatically increased in white males since 1973. And incidences of ESCC and EAC were the lowest and stable in Asian female. Multivariable models showed that patients who were male, or black, or had larger tumors, or positive lymph nodes had an increased risk of death from esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated with surgery had a lower likelihood of death. For ESCC, the black patients had the lowest DSS, while for EAC there were no significant differences in DSS among the ethnic/racial groups. From the Surveillance, Epidemiology, and End Results Program database, patients diagnosed with esophageal cancer from 1998-2013 were identified. Differences in incidences, clinicopathological features, treatments, and disease-specific survival (DSS) in four broad racial/ethnic groups were compared. Histological type distribution between racial groups could be an important consideration in the incidence and the survival trend but other factors could also have an effect.
Evaluation of the Maximum Allowable Cost Program
Lee, A. James; Hefner, Dennis; Dobson, Allen; Hardy, Ralph
1983-01-01
This article summarizes an evaluation of the Maximum Allowable Cost (MAC)-Estimated Acquisition Cost (EAC) program, the Federal Government's cost-containment program for prescription drugs.1 The MAC-EAC regulations which became effective on August 26, 1976, have four major components: (1) Maximum Allowable Cost reimbursement limits for selected multisource or generically available drugs; (2) Estimated Acquisition Cost reimbursement limits for all drugs; (3) “usual and customary” reimbursement limits for all drugs; and (4) a directive that professional fee studies be performed by each State. The study examines the benefits and costs of the MAC reimbursement limits for 15 dosage forms of five multisource drugs and EAC reimbursement limits for all drugs for five selected States as of 1979. PMID:10309857
NASA Astrophysics Data System (ADS)
Kelly, Paige; Clementson, Lesley; Lyne, Vincent
2015-06-01
Sixty years of oceanographic in situ data at Port Hacking (34°S) and Maria Island (42°S) and 15 years of satellite-derived chlorophyll a (chl a) in inshore and offshore waters of southeast Australia show changes in the seasonality and trend of water properties consistent with long-term intensification and southerly extensions of East Australian Current (EAC) water. Decadal analyses reveal that the EAC extension water at Maria Island increased gradually from the 1940s to 1980s, followed by a rapid increase since the 1990s. This acceleration coincided with enhanced winter nitrate, implying increased injections of subantarctic water at Maria Island. Satellite-derived chl a at six coastal sites and offshore companion sites in the western Tasman Sea showed significant inshore-offshore variations in seasonal cycle and long-term trend. After 2004-2005, the Maria Island seasonal cycle became increasingly similar to those of Bass Strait and St. Helens, suggesting that the EAC extension water was extending further southward. Comparative analyses of inshore-offshore sites showed that the presence of EAC extension water declined offshore. Seasonal cycles at Maria Island show a recent shift away from the traditional spring bloom, toward increased winter biomass, and enhanced primary productivity consistent with extensions of warm, energetic EAC extension water and more frequent injections of cooler, fresher nitrate-replete waters. Overall, we find complex temporal, latitudinal, and inshore-offshore changes in multiple water masses, particularly at Maria Island, and changes in primary productivity that will profoundly impact fisheries and ecosystems.
NASA Astrophysics Data System (ADS)
Saif, M.; El-Shafiy, Hoda F.; Mashaly, Mahmoud M.; Eid, Mohamed F.; Nabeel, A. I.; Fouad, R.
2018-03-01
Two novel nano-complexes [(Cu)2(L) (NO3)2(OH2)] (CuH) and [Cu(HL) (OH2)2(NO3)] (CuCTH)were synthesized by hydrothermal method at 200 °C for 48 h in absence and presence of surfactant (CTAB), respectively. Introducing surfactant (CTAB) leads to changing stoichiometric metal/ligand ratio from binuclear (CuH) to mononuclear (CuCTH) nano-complexes. CuH shows irregular nano-flake shape while CuCTH have separately uniform nano-spherical morphology. Thermal analysis revealed that CuCTH is thermally stable in comparison with CuH Nano-complex. CuCTH absorption peak shifted to shorter wavelength (blue shift) and sharpness of the peak also decreased in presence of CTAB. The role of CTAB in the crystal growth is discussed. CuH and CuCTH nano-complexes were tested for their in vitro cytotoxicity against Ehrlich Ascites Carcinoma cell line (E.A.C.). Both nano-complexes effectively inhibited E.A.C. growth with IC50value of 37 and 25 μM for CuH and CuCTH, respectively. The high antitumor activity of CuCTH was attributed to several factors such as spherical morphology, smaller size, chemical structure, and geometry. The LD50 for high cytotoxic CuCTH nano-complex on mice was found to be 100 mg/kg with strong abscess in abdomen side effect. To overcome this side effect, different molar ratio of CuCTH and previously prepared ZnNano-complexes were tested for their in vitrocytotoxicity and in vivo toxicity. Obtained results show that the 2:8 M ratio between CuCTH and Zn nano-complexes gives very low toxicity without any side effects. Also, geometric optimization and conformational analysis were performed using semi-empirical PM3 method. Energy gap (ΔE), dipole moment, and structure activity relationship were performed and discussed.
ERIC Educational Resources Information Center
Trotter, Kay Sudekum; Chandler, Cynthia K.; Goodwin-Bond, Deborah; Casey, Janie
2008-01-01
This study demonstrates the efficacy of Equine Assisted Counseling (EAC) by comparing EAC to classroom-based counseling. Students (n = 164) identified as being at high risk for academic and/or social failure participated in 12 weekly counseling sessions. Within-group paired sample t-test results comparing pre- and post-treatment scores for…
Nakao, Yoshio; Tanigawa, Tohru; Murotani, Kenta; Yamashita, Jun-Ichi
2017-11-01
Otolaryngologists occasionally observe foreign bodies (FB) in the external auditory canal (EAC), although relatively few studies have focused on the role of age in this condition. We retrospectively compared the incidences, outcomes and complications of FB in the EAC in different age groups. The patients at our center included 24 children (19%), 46 adults (37%) and 56 older adults (44%). Compared with adults, older adults were significantly more likely to have FB (peak age 75-79 years), be women (18/46 vs 34/56, P = 0.0461) and be unaware of their FB (18/46 vs 34/56, P = 0.0461). We observed that all EAC FB were more common during the summer, and biotic FB were not observed during the winter. Complications were more common in cases of biotic FB, compared with abiotic FB (5/27 vs 6/99, P = 0.0421). Our findings show that older adults are particularly susceptible to FB, are frequently unaware of their FB and can develop complications. These characteristics should be considered before treating FB in the EAC. Geriatr Gerontol Int 2017; 17: 2131-2135. © 2017 Japan Geriatrics Society.
Gender role conflict and emotional approach coping in men with cancer.
Hoyt, Michael A
2009-10-01
The utility of emotional approach coping (EAC), or expressing and processing emotions, has been equivocal for men. Gender role conflict, or the negative cognitive, emotional and behavioural consequences associated with male gender role socialisation, likely shape coping responses and may negatively affect the efficacy of men's emotion-directed coping efforts and adjustment to cancer. Perceptions of receptiveness of one's interpersonal environment may be particularly important to the effectiveness of EAC. This study examined the relationships among EAC, gender role conflict, and distress in a group of 183 men with cancer. Structural equation modelling revealed that higher gender role conflict was associated with lower emotional expression, which in turn was associated with greater distress. Gender role conflict was not related to emotional processing. Higher gender role conflict also was associated directly with more distress. In subsequent analyses, social constraints and age were examined as possible moderators of EAC. Emotional expression was related to more psychological distress for those in highly constrained environments; and emotional processing was associated with more distress with younger age. Emotional expression may be particularly affected by social influences related to gender and social receptivity. More research is needed to better distinguish constructive and unconstructive emotional processing.
Adhershitha, A. R.; Anilkumar, S.; Rajesh, C.; Mohan, Deepak C.
2016-01-01
Acquired external auditory canal (EAC) atresia is an infrequent entity which can originate from a number of different causes including trauma, infection, neoplasia, inflammation, and radiotherapy. Posttraumatic atresias are exceptionally rare, only 10% of atresias are attributed to trauma in most of the series. The management of stenosis of the EAC is challenging as it is associated with residual hearing loss and late recurrence. Traditional stents often occlude the EAC, resulting in a temporary conductive hearing loss. This case report describes the technique of fabrication of a wide-bored acrylic stent which attained additional retention from the folds of the auricle. The customized earmold stent effectively prevented restenosis, while the large bore provided ventilation and improved hearing subjectively during the stenting period. PMID:27746605
DOE Office of Scientific and Technical Information (OSTI.GOV)
Abd-El Fattah, Amal A.
2017-02-01
Carbonic anhydrase inhibitors have emerged in the past few years as an interesting candidate for the development of novel unconventional strategies. Despite their effect in tumor regression via inhibition of tumor acidification, their potential role is not yet fully elucidated. Herein, we investigated whether acetazolamide (AZ) could modulate imatinib (IM) anticancer activity, both in breast cancer cells (T47D) and in isolated tumor specimens of Ehrlich ascites carcinoma (EAC). The impact of this combination on angiogenesis was evidenced by decreasing PDGF-A expression and enhancing that of TSP-1. In the meantime, AZ significantly suppressed IM-induced attenuation of VEGF secretion in T47D cells,more » most probably due to NO inhibition. The combination also dramatically decreased the metastatic activity of T47D cells by mitigating the protein levels of MMP-2 and -9 and phosphorylation of p38 MAPK, while increasing the expression of TIMP-1 and -2. In addition, a strong proapoptotic effect was observed in T47D cells after combining AZ and IM in terms of increased caspase-9 and -3 activities. Interestingly, these results were confirmed by the reduction in the isolated tumor volume, MVD, Ki-67 and VEGF expression. Eventually, the study provides a new therapeutic strategy for treating cancer. - Highlights: • A novel combination of imatinib and a carbonic anhydrase was studied. • The impact was evaluated in T47D cells and EAC-bearing mice. • The interaction suppressed PDGF-A and VEGF while enhanced TSP-1. • MMPs and p38 MAPK phosphorylation were suppressed while TIMPs were enhanced. • The interaction triggered caspase-9 and -3 activation.« less
Parasa, Sravanthi; Vennalaganti, Sreekar; Gaddam, Srinivas; Vennalaganti, Prashanth; Young, Patrick; Gupta, Neil; Thota, Prashanthi; Cash, Brooks; Mathur, Sharad; Sampliner, Richard; Moawad, Fouad; Lieberman, David; Bansal, Ajay; Kennedy, Kevin F; Vargo, John; Falk, Gary; Spaander, Manon; Bruno, Marco; Sharma, Prateek
2018-04-01
A system is needed to determine the risk of patients with Barrett's esophagus for progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). We developed and validated a model to determine of progression to HGD or EAC in patients with BE, based on demographic data and endoscopic and histologic findings at the time of index endoscopy. We performed a longitudinal study of patients with BE at 5 centers in United States and 1 center in Netherlands enrolled in the Barrett's Esophagus Study database from 1985 through 2014. Patients were excluded from the analysis if they had less than 1 year of follow-up, were diagnosed with HGD or EAC within the past year, were missing baseline histologic data, or had no intestinal metaplasia. Seventy percent of the patients were used to derive the model and 30% were used for the validation study. The primary outcome was development of HGD or EAC during the follow-up period (median, 5.9 years). Survival analysis was performed using the Kaplan-Meier method. We assigned a specific number of points to each BE risk factor, and point totals (scores) were used to create categories of low, intermediate, and high risk. We used Cox regression to compute hazard ratios and 95% confidence intervals to determine associations between risk of progression and scores. Of 4584 patients in the database, 2697 were included in our analysis (84.1% men; 87.6% Caucasian; mean age, 55.4 ± 20.1 years; mean body mass index, 27.9 ± 5.5 kg/m 2 ; mean length of BE, 3.7 ± 3.2 cm). During the follow-up period, 154 patients (5.7%) developed HGD or EAC, with an annual rate of progression of 0.95%. Male sex, smoking, length of BE, and baseline-confirmed low-grade dysplasia were significantly associated with progression. Scores assigned identified patients with BE that progressed to HGD or EAC with a c-statistic of 0.76 (95% confidence interval, 0.72-0.80; P < .001). The calibration slope was 0.9966 (P = .99), determined from the validation cohort. We developed a scoring system (Progression in Barrett's Esophagus score) based on male sex, smoking, length of BE, and baseline low-grade dysplasia that identified patients with BE at low, intermediate, and high risk for HGD or EAC. This scoring system might be used in management of patients. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
Shawali, Ahmad S; Sherif, Sherif M; Darwish, Manal A A; El-merzabani, Mahmoud M
2010-01-01
A new series of 3-(1,3-disubstituted-1H-pyrazole-4-carbonyl)-1,7-diphenyl-[1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones 4 was prepared by reaction of the enaminone 2 with hydrazonoyl halides 3. The preliminary screening for antitumor activity of the synthesized compounds was carried out against Ehrlich Ascites Carcinoma tumor cells. The results revealed that the studied compounds 4 have low or no antitumor activity towards EAC tumor cells.
NASA Astrophysics Data System (ADS)
Kelly, Paige; Clementson, Lesley; Davies, Claire; Corney, Stuart; Swadling, Kerrie
2016-10-01
Southeastern Australia is a 'hotspot' for oceanographic change. Here, rapidly increasing sea surface temperatures, rising at more than double the global trend, are largely associated with a southerly extension of the East Australian Current (EAC) and its eddy field. Maria Island, situated at the southern end of the EAC extension at 42°S, 148°E, has been used as a site to study temperature-driven biological trends in this region of accelerated change. Zooplankton have short life cycles (usually < 1 year) and are highly sensitive to environmental change, making them an ideal indicator of the biological effects of an increased southward flow of the EAC. Data from in-situ net drops and the Continuous Plankton Recorder (CPR), collected since 2009, together with historical zooplankton abundance data, have been analysed in this study. Like the North Atlantic, zooplankton communities of southeastern Australia are responding to increased temperatures through relocation, long-term increases in warm-water species and a shift towards a zooplankton community dominated by small copepods. The biological trends present evidence of extended EAC influence at Maria Island into autumn and winter months, which has allowed for the rapid establishment of warm-water species during these seasons, and has increased the similarity between Maria Island and the more northerly Port Hacking zooplankton community. Generalised Linear Models (GLM) suggest the high salinity and low nutrient properties of EAC-water to be the primary drivers of increasing abundances of warm-water species off southeastern Australia. Changes in both the species composition and size distribution of the Maria Island zooplankton community will have effects for pelagic fisheries. This study provides an indication of how zooplankton communities influenced by intensifying Western Boundary currents may respond to rapid environmental change.
Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.
Sun, Xiangqing; Elston, Robert; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia I; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh
2016-07-01
Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.
ERIC Educational Resources Information Center
Bourdon, Francoise
2005-01-01
The translation into French of the Encoded Archival Context (EAC) DTD tag library has been in progress for a few months. It is being carried out by a group of experts gathered by AFNOR, the French national standards agency. The main goal of this group is to foster the interoperability of authority data between archives, libraries and museums, and…
Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma.
Wang, Jeremy; Liu, Wendy; Parikh, Keyur; Post, Anthony Benjamin
2017-02-01
Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.
The electron donating capacity of biochar is dramatically underestimated
Prévoteau, Antonin; Ronsse, Frederik; Cid, Inés; Boeckx, Pascal; Rabaey, Korneel
2016-01-01
Biochars have gathered considerable interest for agronomic and engineering applications. In addition to their high sorption ability, biochars have been shown to accept or donate considerable amounts of electrons to/from their environment via abiotic or microbial processes. Here, we measured the electron accepting (EAC) and electron donating (EDC) capacities of wood-based biochars pyrolyzed at three different highest treatment temperatures (HTTs: 400, 500, 600 °C) via hydrodynamic electrochemical techniques using a rotating disc electrode. EACs and EDCs varied with HTT in accordance with a previous report with a maximal EAC at 500 °C (0.4 mmol(e−).gchar−1) and a large decrease of EDC with HTT. However, while we monitored similar EAC values than in the preceding study, we show that the EDCs have been underestimated by at least 1 order of magnitude, up to 7 mmol(e−).gchar−1 for a HTT of 400 °C. We attribute this existing underestimation to unnoticed slow kinetics of electron transfer from biochars to the dissolved redox mediators used in the monitoring. The EDC of other soil organic constituents such as humic substances may also have been underestimated. These results imply that the redox properties of biochars may have a much bigger impact on soil biogeochemical processes than previously conjectured. PMID:27628746
Villeneuve, L; Wang, Rong-Lin; Bencic, David C; Biales, Adam D; Martinović, Dalma; Lazorchak, James M; Toth, Gregory; Ankley, Gerald T
2009-08-01
As part of a research effort examining system-wide responses of the hypothalamic-pituitary-gonadal (HPG) axis in fish to endocrine-active chemicals (EACs) with different modes of action, zebrafish (Danio rerio) were exposed to 25 or 100 microg/L of the aromatase inhibitor fadrozole for 24, 48, or 96 h. Global transcriptional response in brain and ovarian tissue of fish exposed to 25 microg/L of fadrozole was compared to that in control fish using a commercially available, 22,000-gene oligonucleotide microarray. Transcripts altered in brain were functionally linked to differentiation, development, DNA replication, and cell cycle. Additionally, multiple genes associated with the one-carbon pool by folate pathway (KEGG 00670) were significantly up-regulated. Transcripts altered in ovary were functionally linked to cell-cell adhesion, extracellular matrix, vasculogenesis, and development. Promoter motif analysis identified GATA-binding factor 2, Ikaros 2, alcohol dehydrogenase gene regulator 1, myoblast-determining factor, and several heat shock factors as being associated with coexpressed gene clusters that were differentially expressed following exposure to fadrozole. Based on the transcriptional changes observed, it was hypothesized that fadrozole elicits neurodegenerative stress in brain tissue and that fish cope with this stress through proliferation of radial glial cells. Additionally, it was hypothesized that changes of gene expression in the ovary of fadrozole-exposed zebrafish reflect disruption of oocyte maturation and ovulation because of impaired vitellogenesis. These hypotheses and others derived from the microarray results provide a foundation for future studies aimed at understanding responses of the HPG axis to EACs and other chemical stressors.
Bhattacharjee, Arin; Basu, Abhishek; Biswas, Jaydip; Sen, Tuhinadri; Bhattacharya, Sudin
2017-01-01
Cyclophosphamide (CP) is one of the widely used anticancer agents; however, it has serious deleterious effects on normal host cells due to its nonspecific action. The essential trace element Selenium (Se) is suggested to have chemopreventive and chemotherapeutic efficacy and currently used in pharmaceutical formulations. Previous report had shown Nano-Se could protect CP-induced hepatotoxicity and genotoxicity in normal Swiss albino mice; however, its role in cancer management is still not clear. The aim of present study is to investigate the chemoprotective efficacy of Nano-Se against CP-induced toxicity as well as its chemoenhancing capability when used along with CP in Swiss albino mice against Ehrlich's ascites carcinoma (EAC) cells. CP was administered (25 mg/kg b.w., i.p.) and Nano-Se was given (2 mg Se/kg b.w., p.o.) in concomitant and pretreatment schedule. Increase levels of serum hepatic marker, hepatic lipid peroxidation, DNA damage, and chromosomal aberration in CP-treated mice were significantly (P < 0.05) reversed by Nano-Se. The lowered status of various antioxidant enzymes in tumor-bearing mice after CP treatment was also effectively increased by Nano-Se. Administration of Nano-Se along with CP caused a significant reduction in tumor volume, packed cell volume, viable tumor cell count, and increased the survivability of the tumor-bearing hosts. The results suggest that Nano-Se exhibits significant antitumor and antioxidant effects in EAC-bearing mice. The potential for Nano-Se to ameliorate the CP-evoked toxicity as well as to improve the chemotherapeutic effect could have beneficial implications for patients undergoing chemotherapy with CP.
EAC trains its first international astronaut class.
Bolender, Hans; Bessone, Loredana; Schoen, Andreas; Stevenin, Herve
2002-11-01
After several years of planning and preparation, ESA's ISS training programme has become operational. Between 26 August and 6 September, the European Astronaut Centre (EAC) near Cologne gave the first ESA advanced training course for an international ISS astronaut class. The ten astronauts who took part--two from NASA, four from Japan and four from ESA--had begun their advanced training programme back in 2001 with sessions at the Johnson Space Center (JSC) in Houston and at the Japanese Training Centre in Tsukuba. During their stay in Cologne, the ten astronauts participated in a total of 33 classroom lessons and hands-on training sessions, which gave them a detailed overview of the systems and subsystems of the Columbus module, the Automated Transfer Vehicle (ATV), and the related crew operations tasks. They were also introduced to the four ESA experiment facilities to be operated inside the Columbus module. After their first week of training at EAC, the astronauts were given the opportunity to see the flight model of the Columbus module being integrated at the site of ESA's ISS prime contractor, Astrium in Bremen. The second week of training at EAC included hands-on instruction on the Columbus Data Management System (DMS) using the recently installed Columbus Crew Training Facility. In preparation for the first advanced crew training session at EAC, two Training Readiness Reviews (TRR) were conducted there in June and August. These reviews were supported by training experts and astronauts from NASA, NASDA and CSA (Canada), who were introduced to ESA's advanced training concept and the development process, and then analysed and evaluated the training flow, content and instructional soundness of lessons and courses, as well as the fidelity of the training facilities and the skills of the ESA training instructors. The International Training Control Board (ITCB), made up of representatives from all of the ISS International Partners and mandated to control and coordinate all multilateral training for ISS crew and ground-support personnel, testified to ESA's readiness to provide Advanced Training by declaring the EAC TRR successful. The completion of this first training course was therefore a good opportunity for the Astronaut Training Division to assess the status of its training programme. The comments and recommendations of the training experts and the astronauts who took part have been carefully evaluated and the results are being fed back into the ongoing training development process.
Characterising primary productivity measurements across a dynamic western boundary current region
NASA Astrophysics Data System (ADS)
Everett, Jason D.; Doblin, Martina A.
2015-06-01
Determining the magnitude of primary production (PP) in a changing ocean is a major research challenge. Thousands of estimates of marine PP exist globally, but there remain significant gaps in data availability, particularly in the Southern Hemisphere. In situ PP estimates are generally single-point measurements and therefore we rely on satellite models of PP in order to scale up over time and space. To reduce the uncertainty around the model output, these models need to be assessed against in situ measurements before use. This study examined the vertically-integrated productivity in four water-masses associated with the East Australian Current (EAC), the major western boundary current (WBC) of the South Pacific. We calculated vertically integrated PP from shipboard 14C PP estimates and then compared them to estimates from four commonly used satellite models (ESQRT, VGPM, VGPM-Eppley, VGPM-Kameda) to assess their utility for this region. Vertical profiles of the water-column show each water-mass had distinct temperature-salinity signatures. The depth of the fluorescence-maximum (fmax) increased from onshore (river plume) to offshore (EAC) as light penetration increased. Depth integrated PP was highest in river plumes (792±181 mg C m-2 d-1) followed by the EAC (534±116 mg C m-2 d-1), continental shelf (140±47 mg C m-2 d-1) and cyclonic eddy waters (121±4 mg C m-2 d-1). Surface carbon assimilation efficiency was greatest in the EAC (301±145 mg C (mg Chl-a)-1 d-1) compared to other water masses. All satellite primary production models tested underestimated EAC PP and overestimated continental shelf PP. The ESQRT model had the highest skill and lowest bias of the tested models, providing the best first-order estimates of PP on the continental shelf, including at a coastal time-series station, Port Hacking, which showed considerable inter-annual variability (155-2957 mg C m-2 d-1). This work provides the first estimates of depth integrated PP associated with the East Australian Current in temperate Australia. The ongoing intensification of all WBCs makes it critical to understand the variability in PP at the regional scale. More accurate predictions in the EAC region will require vertically-resolved in situ productivity and bio-optical measurements across multiple time scales to allow development of other models which simulate dynamic ocean conditions.
Williet, Nicolas; Tournier, Quentin; Vernet, Chloé; Dumas, Olivier; Rinaldi, Leslie; Roblin, Xavier; Phelip, Jean-Marc; Pioche, Mathieu
2018-04-26
Yield of Endocuff-assisted colonoscopy (EAC) compared with standard colonoscopy is conflicting in terms of adenoma detection rate (ADR). A meta-analysis of randomized controlled trials (RCTs) appears necessary. PubMed and Google Scholar were searched in December 2017. Abstracts from Digestive Disease Week and United European Gastroenterology Week meetings were also searched to 2017. All RCTs comparing EAC with standard colonoscopy were included. Analysis was conducted by using the Mantel-Haenszel models. Heterogeneity was quantified using the I 2 test. Of the 265 articles reviewed, 12 RCTs were included, with a total of 8376 patients (EAC group 4225; standard colonoscopy group 4151). In the meta-analysis, ADR was significantly increased in the EAC group vs. the standard colonoscopy group (41.3 % vs. 34.2 %; risk ratio [RR] = 1.20, 95 % confidence interval [CI] 1.06 to 1.36; P = 0.003; I 2 = 79 %), especially for operators with low-to-moderate ADRs (< 35 %): RR = 1.51, 95 %CI 1.35 to 1.69; P < 0.001; I 2 = 43 %). In contrast, this benefit was not reached for operators with high ADRs (> 45 %): RR = 1.01, 95 %CI 0.93 to 1.09; P = 0.87; I 2 = 0.0 %). The mean number of adenomas per patient tended to be higher with EAC (mean difference = 0.11 adenomas/patient, 95 %CI - 0.17 to 0.38). Similar results were shown for polyp detection rates (61.6 % vs. 51.4 %; RR = 1.20, 95 %CI 1.06 to 1.36; P = 0.004). Use of the Endocuff did not impact the cecal intubation rate (95.1 % vs. 95.7 %; P = 0.08), or the procedure time compared with standard colonoscopy. Adverse events related to Endocuff were rare and exclusively mild mucosal erosion (4.0 %; 95 %CI 2.0 % to 8.0 %). With moderate-quality evidence, this study showed an improvement in ADR with EAC without major adverse events, especially for operators with low-to-moderate ADRs. © Georg Thieme Verlag KG Stuttgart · New York.
Cost and Schedule Benchmarks for Defense Acquisition Contracts
1994-09-01
and schedule deviations early Knepp & S -curves for cost S -curves couldn’t Stroble/1993 control be used Terry & EAC Indices SCI-based EAC is...completed and on-going contracts from the early 1970’ s to date. Some of the fields in the database used in determining the status of cost overruns and...Measurement Data (Christensen, 1992:20). Christensen Article David S . Christensen published an analysis of cost overruns on DoD acquisition contracts
NASA Astrophysics Data System (ADS)
MacDonald, H. S.; Roughan, M.; Baird, M. E.; Wilkin, J.
2013-01-01
NASA Astrophysics Data System (ADS)
Toderi, Martín A.; Castellini, Horacio V.; Riquelme, Bibiana D.
2017-01-01
The study of red blood cell (RBC) aggregation is of great interest because of its implications for human health. Altered RBC aggregation can lead to microcirculatory problems as in vascular pathologies, such as hypertension and diabetes, due to a decrease in the erythrocyte surface electric charge and an increase in the ligands present in plasma. The process of erythrocyte aggregation was studied in stasis situation (free shear stresses), using an optical chip based on the laser transmission technique. Kinetic curves of erythrocyte aggregation under different conditions were obtained, allowing evaluation and characterization of this process. Two main characteristics of blood that influence erythrocyte aggregation were analyzed: the erythrocyte surface anionic charge (EAC) after digestion with the enzyme trypsin and plasmatic protein concentration in suspension medium using plasma dissolutions in physiological saline with human albumin. A theoretical approach was evaluated to obtain aggregation and disaggregation ratios by syllectograms data fitting. Sensible parameters (Amp100, t) regarding a reduced erythrocyte EAC were determined, and other parameters (AI, M-Index) resulted that are representative of a variation in the plasmatic protein content of the suspension medium. These results are very useful for further applications in biomedicine.
Kasangana, Pierre Betu; Haddad, Pierre Selim; Stevanovic, Tatjana
2015-01-01
In order to evaluate the therapeutic potential of polyphenolic extracts from root bark of M. arboreus, we have determined the content of various polyphenols in aqueous and ethanol (EtOH) extract as well as two sub-fractions of the latter: ethyl acetate (EAc) and hexane (Hex). The total phenols, flavonoids, hydroxycinnamic acids and proanthocyanidins have been determined for all studied extracts/fractions by spectrophotometric methods. Both TP content (331.5 ± 2.5 mg GAE/g) and HCA content (201 ± 1.5 mg CAE/g) were determined to be the highest in EAc fraction of EtOH extract. All studied extracts were however determined to have a low content in flavonoids. The determination of antioxidant capacities of the studied extracts has also been performed by the following in vitro antioxidant tests: DPPH scavenging, phosphomolybdenum method and oxygen radical absorbance (ORACFl and ORACPRG) assay. The results of the DPPH free radical and ORACFl assays showed that there is no significant difference between the EAc fraction and Oligopin®, but the EAc fraction exhibited the highest antioxidant capacity as determined by the phosphomolybdenium method. In addition, the EtOH extract was determined to have the same antioxidant efficiency as the synthetic antioxidant BHT or commercial extract Oligopin® by phosphomolybdenum method. On the other hand, a positive correlation (r < 0.6) was found between different classes of polyphenols and the results of the phosphomolybdenum method, ORACFl as well as ORACPRG, except for the DPPH assay, for which a negative correlation was indicated (r < 0.62). Interestingly, it seems that the content in hydroxycinnamic acids played a big role in all assays with r < 0.9. According to the present study, EAc fraction and EtOH extract should be further studied for the potential use in the pharmaceutical and food industry. PMID:26783713
Murphy, Lisa A; Panek, Cynthia M; Bianco, Domenico; Nakamura, Reid K
2017-01-01
To describe the utility of Yunnan Baiyao (YB) alone or in combination with epsilon aminocaproic acid (EAC) for the treatment of dogs with echocardiographically identified right atrial (RA) masses and pericardial effusion (PE). Retrospective case-controlled study. Two private practice referral hospitals. Client-owned dogs with RA masses and PE identified echocardiographically over a 3-year period. None. There were 67 dogs identified with RA masses and PE during the study period. Sixteen dogs were treated with YB alone while 8 dogs were treated with YB in combination with EAC in addition to pericardiocentesis. Forty-three dogs were treated with pericardiocentesis alone and were considered to be the control group. There was no difference between the groups in regards to signalment, physical examination abnormalities, and diagnostic test results on presentation. There was no significant difference between the 2 groups with respect to number of pericardiocenteses performed and there were no side effects attributed to the YB or EAC in any of the dogs. Median time to recurrence of clinical signs was not significantly different between the treatment (12 d, range 1-186 d) and control group (14.5 d, range 1-277 d). The median survival of dogs treated with YB alone or in combination with EAC (18 d, range 1-186 d) was also not significantly improved compared to dogs treated with pericardiocenteses alone (16 d, range 1-277 d). This study suggests YB alone or in combination with EAC is relatively safe but does not significantly delay recurrence of clinical signs or improve survival in dogs with RA masses and PE. Due to the small cohort size, further prospective studies evaluating these drugs and their effects on hemostasis in dogs with RA masses and PE are warranted. © Veterinary Emergency and Critical Care Society 2016.
Improved adenoma detection with Endocuff Vision: the ADENOMA randomised controlled trial.
Ngu, Wee Sing; Bevan, Roisin; Tsiamoulos, Zacharias P; Bassett, Paul; Hoare, Zoë; Rutter, Matthew D; Clifford, Gayle; Totton, Nicola; Lee, Thomas J; Ramadas, Arvind; Silcock, John G; Painter, John; Neilson, Laura J; Saunders, Brian P; Rees, Colin J
2018-01-23
Low adenoma detection rates (ADR) are linked to increased postcolonoscopy colorectal cancer rates and reduced cancer survival. Devices to enhance mucosal visualisation such as Endocuff Vision (EV) may improve ADR. This multicentre randomised controlled trial compared ADR between EV-assisted colonoscopy (EAC) and standard colonoscopy (SC). Patients referred because of symptoms, surveillance or following a positive faecal occult blood test (FOBt) as part of the Bowel Cancer Screening Programme were recruited from seven hospitals. ADR, mean adenomas per procedure, size and location of adenomas, sessile serrated polyps, EV removal rate, caecal intubation rate, procedural time, patient experience, effect of EV on workload and adverse events were measured. 1772 patients (57% male, mean age 62 years) were recruited over 16 months with 45% recruited through screening. EAC increased ADR globally from 36.2% to 40.9% (P=0.02). The increase was driven by a 10.8% increase in FOBt-positive screening patients (50.9% SC vs 61.7% EAC, P<0.001). EV patients had higher detection of mean adenomas per procedure, sessile serrated polyps, left-sided, diminutive, small adenomas and cancers (cancer 4.1% vs 2.3%, P=0.02). EV removal rate was 4.1%. Median intubation was a minute quicker with EAC (P=0.001), with no difference in caecal intubation rate or withdrawal time. EAC was well tolerated but caused a minor increase in discomfort on anal intubation in patients undergoing colonoscopy with no or minimal sedation. There were no significant EV adverse events. EV significantly improved ADR in bowel cancer screening patients and should be used to improve colonoscopic detection. NCT 02552017, Results; ISRCTN 11821044, Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Zaidi, Ali H; Kosovec, Juliann E; Matsui, Daisuke; Omstead, Ashten N; Raj, Moses; Rao, Rohit R; Biederman, Robert W W; Finley, Gene G; Landreneau, Rodney J; Kelly, Ronan J; Jobe, Blair A
2017-07-01
The purpose of the current study is to determine the efficacy of a PI3K/mTOR dual inhibitor, LY3023414, on established EAC in an in vivo model. Esophageal adenocarcinoma (EAC) is a highly lethal cancer with limited treatment options. The PI3K/mTOR pathway is upregulated in EAC and may be a target for novel therapies. Esophagojejunostomy was performed on Sprague-Dawley rats to induce carcinogenesis, and LY3023414 was cyclically administered intraperitoneally between 32 and 40 weeks postsurgery to treatment animals. Magnetic resonance imaging (MRI) and histology were used to determine clinical response. Immunohistochemistry, immunofluorescence, and Western blot were used to validate apoptosis by cleaved caspase-3, proliferation by Ki67, and pathway inhibition, respectively. Mean MRI tumor volume increased by 109.2% in controls (n = 32) and decreased by 56.8% in treatment animals (n=17) (P < 0.01). Treatment with LY3023414 demonstrated tumor volume increase in 0% (control = 46.4%) (P < 0.01), decrease in 58.8% (control = 7.1%) (P < 0.01), and stable volume in 41.2% (control = 46.4%) (P = 0.77). EAC prevalence in controls increased by 25%; whereas, prevalence in treatment animals decreased by 29.4% (P < 0.01). Approximately, 75% of treatment animals presenting with residual masses on MRI had a histological response >50%. Increased apoptosis by cleaved caspase-3 (P = 0.03) and decreased proliferation by Ki67 (P < 0.01) were demonstrated in the treatment arm, when compared with the control arm. On Western blot analysis of pathway checkpoints, p-mTOR (p=0.03) and PI3K-α (P = 0.04) were downregulated in treatment responsive residual tumors, when compared with controls. LY3023414 demonstrates efficacy against EAC in a preclinical model, establishing the rationale for clinical testing.
A Model for Understanding the Relationship Between Transaction Costs and Acquisition Cost Breaches
2014-04-30
an assistant professor and received a BA in anthropology and a BA and MA in economics (2004) and a PhD in political economy and public policy (2008...between transaction costs and cost overruns. Biggs (2013) showed that as the EAC SE/PM cost ratio rises there is a statistically significant corresponding...Estimate at Completion ( EAC ) is the sum of the ACWP and the estimate to completion (ETC) for the remaining work. The ETC can be calculated using the cost
Using Earned Value Information to Predict Program Cancellation
2014-09-02
models is that when there is high cost growth in the EAC reported by the contractor, programs run far larger risks of cancellation. We find less robust...for MDAPs. Our most significant finding across models is that when there is high cost growth in the EAC reported by the contractor, programs run far...professor and received a BA in anthropology and a BA and MA in economics (2004) and a PhD in political economy and public policy (2008) from the
Warren, Andrew; Cheetham, R. Keira; Northen, Helen; O’Donovan, Maria; Malhotra, Shalini; di Pietro, Massimiliano; Ivakhno, Sergii; He, Miao; Weaver, Jamie M.J.; Lynch, Andy G.; Kingsbury, Zoya; Ross, Mark; Humphray, Sean; Bentley, David; Fitzgerald, Rebecca C.
2015-01-01
The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett’s esophagus and EAC samples, together with one in-depth Barrett’s esophagus case-study sampled over time and space, we have provided new insights on the following aspects: i) Barrett’s esophagus is polyclonal and highly mutated even in the absence of dysplasia; ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett’s esophagus; and iii) despite differences in specific coding mutations the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett’s epithelium and a molecular Cytosponge™ technique overcomes sampling bias and has capacity to reflect the entire clonal architecture. PMID:26192915
Internal Waves in the East Australian Current
NASA Astrophysics Data System (ADS)
Alford, Matthew H.; Sloyan, Bernadette M.; Simmons, Harper L.
2017-12-01
Internal waves, which drive most ocean turbulence and add "noise" to lower-frequency records, interact with low-frequency current systems and topography in yet poorly known ways. Taking advantage of a heavily instrumented, 14 month mooring array, internal waves in the East Australian Current (EAC) are examined for the first time. Internal wave horizontal kinetic energy (HKE) is within a factor of 2 of the Garrett-Munk (1976) spectrum. Continuum internal waves, near-inertial waves, and internal tides together constitute a significant percentage of the total velocity variance. Mode-1 internal tide energy fluxes are southward and much smaller than energy times group velocity, consistent with reflection at the continental slope of incident waves generated from near New Caledonia and the Solomon Islands. Internal tide HKE is highly phase variable, consistent with refraction by the variable EAC. Mode-1 near-inertial wave energy fluxes are of comparable magnitude and are equatorward and episodic, consistent with generation by storms farther poleward. These processes are considered together in the complex environment of the EAC.
9th annual European Antibody Congress, November 11-13, 2013, Geneva, Switzerland.
Reichert, Janice M; Beck, Alain; Lugovskoy, Alexey A; Wurch, Thierry; Coats, Steven; Brezski, Randall J
2014-01-01
The annual European Antibody Congress (EAC) has traditionally been the key event for updates on critical scientific advances in the antibody field, and 2013 was no exception. Organized by Terrapinn, the well-attended meeting featured presentations on considerations for developing antibodies and antibody-like therapeutics, with separate tracks for antibody-drug conjugates, naked antibodies, and multispecific antibodies or protein scaffolds. The overall focus of the EAC was current approaches to enhance the functionality of therapeutic antibodies or other targeted proteins, with the ultimate goal being improvement of the safety and efficacy of the molecules as treatments for cancer, immune-mediated disorders and other diseases. Roundtable discussion sessions gave participants opportunities to engage in group discussions with industry leaders from companies such as Genmab, Glenmark Pharmaceuticals, MedImmune, Merrimack Pharmaceuticals, and Pierre Fabre. As the 2013 EAC was co-located with the World Biosimilar Congress, participants also received an update on European Medicines Agency guidelines and thoughts on the future direction and development of biosimilar antibodies in the European Union.
Qumseya, Bashar J; Brown, Jessica; Abraham, Merna; White, Donna; Wolfsen, Herbert; Gupta, Neil; Vennalaganti, Prashanth; Sharma, Prateek; Wallace, Michael B
2015-04-01
The role of EUS among patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD) or suspected mucosal carcinoma is controversial. To define the role of EUS in detecting advanced disease among patients with BE. Systematic review and meta-analysis. MEDLINE, Embase, Web of Science, and Cochrane Central databases. Patients with BE and HGD or esophageal adenocarcinoma (EAC) who were referred for endoscopic evaluation and underwent EUS. EUS. Pooled proportion of patients with advanced EAC identified by EUS among patients with BE who are referred for HGD or EAC (with or without visible lesions). Forest plots were used to contrast effect sizes in each of the studies and random effect models when tests of heterogeneity were significant (I(2) > 50% or P < .1 for the Q statistic). Of 1278 articles, 47 were reviewed in full text, and 11 articles met the inclusion criteria, including a total of 656 patients. Based on a random-effects model, the proportion of patients with advanced disease detected on EUS was 14% (95% confidence interval, 8%-22%; P < .0001). In a subanalysis, the pooled proportion of patients with advanced disease on EUS in the absence of nodules was 4% (95% confidence interval, 2%-6%, P < .0001). Significant heterogeneity among studies. EUS will result in a change in the therapeutic approach among in a significant minority of patients with BE who are referred for HGD or EAC. Copyright © 2015. Published by Elsevier Inc.
Flows in the Tasman Front south of Norfolk Island
NASA Astrophysics Data System (ADS)
Sutton, Philip J. H.; Bowen, Melissa
2014-05-01
The Tasman Front is a narrow band of eastward flowing subtropical water crossing the Tasman Sea from Australia to North Cape, New Zealand. It is the link between the two subtropical western boundary currents of the South Pacific, the East Australian Current (EAC) off eastern Australia, and the East Auckland Current (EAUC) off northeastern New Zealand. Here we report the first direct measurements of flow in the Tasman Front from a moored array deployed across gaps in the submarine ridges south of Norfolk Island and hydrographic and ADCP measurements during the deployment and recovery voyages. The mean flow through the array over July 2003 to August 2004 was found to be eastward only in the upper 800 m with a transport of ˜6 Sv. Below 800 m a weak westward mean flow (˜1.5 Sv) was measured, associated with Antarctic Intermediate Water (AAIW). Using sea surface height to account for additional transport south of the moored array results in a total mean eastward transport between Norfolk Island and North Cape, New Zealand of ˜8 Sv, varying between -4 and 18 Sv. The measurements show that the Tasman Front is much shallower than either the EAC or EAUC, both of which extend below 2000 m depth, has less transport than either the EAC or EAUC and has instances of flow reversal. Thus, the Tasman Front is a weaker connection between the EAC and EAUC than the paradigm of a contiguous South Pacific western boundary current system would suggest.
Intracochlear pressure measurements during acoustic shock wave exposure.
Greene, Nathaniel T; Alhussaini, Mohamed A; Easter, James R; Argo, Theodore F; Walilko, Tim; Tollin, Daniel J
2018-05-19
Injuries to the peripheral auditory system are among the most common results of high intensity impulsive acoustic exposure. Prior studies of high intensity sound transmission by the ossicular chain have relied upon measurements in animal models, measurements at more moderate sound levels (i.e. < 130 dB SPL), and/or measured responses to steady-state noise. Here, we directly measure intracochlear pressure in human cadaveric temporal bones, with fiber optic pressure sensors placed in scala vestibuli (SV) and tympani (ST), during exposure to shock waves with peak positive pressures between ∼7 and 83 kPa. Eight full-cephalic human cadaver heads were exposed, face-on, to acoustic shock waves in a 45 cm diameter shock tube. Specimens were exposed to impulses with nominal peak overpressures of 7, 28, 55, & 83 kPa (171, 183, 189, & 192 dB pSPL), measured in the free field adjacent to the forehead. Specimens were prepared bilaterally by mastoidectomy and extended facial recess to expose the ossicular chain. Ear canal (EAC), middle ear, and intracochlear sound pressure levels were measured with fiber-optic pressure sensors. Surface-mounted sensors measured SPL and skull strain near the opening of each EAC and at the forehead. Measurements on the forehead showed incident peak pressures approximately twice that measured by adjacent free-field and EAC entrance sensors, as expected based on the sensor orientation (normal vs tangential to the shock wave propagation). At 7 kPa, EAC pressure showed gain, calculated from the frequency spectra, consistent with the ear canal resonance, and gain in the intracochlear pressures (normalized to the EAC pressure) were consistent with (though somewhat lower than) previously reported middle ear transfer functions. Responses to higher intensity impulses tended to show lower intracochlear gain relative to EAC, suggesting sound transmission efficiency along the ossicular chain is reduced at high intensities. Tympanic membrane (TM) rupture was observed following nearly every exposure 55 kPa or higher. Intracochlear pressures reveal lower middle-ear transfer function magnitudes (i.e. reduced gain relative to the ear canal) for high sound pressure levels, thus revealing lower than expected cochlear exposure based on extrapolation from cochlear pressures measured at more moderate sound levels. These results are consistent with lowered transmissivity of the ossicular chain at high intensities, and are consistent with our prior report measuring middle ear transfer functions in human cadaveric temporal bones with high intensity tone pips. Copyright © 2018 Elsevier B.V. All rights reserved.
Viwithan, a Standardized Withania somnifera Root Extract Induces Apoptosis in Murine Melanoma Cells
Sudeep, H.V.; Gouthamchandra, K.; Venkatesh, B. J.; Prasad, K. Shyam
2017-01-01
Background: Withania somnifera is an Indian medicinal herb known for the multipotential ability to cure various therapeutic ailments as described in the ayurvedic system of medicine. Objective: In the present study, we have evaluated the antiproliferative activity of a standardized W. somnifera root extract (Viwithan) against different human and murine cancer cell lines. Materials and Methods: The cytotoxicity of Viwithan was determined using thiazolyl blue tetrazolium blue assay and crystal violet staining. The apoptotic changes in B16F1 cells following treatment with Viwithan were observed by acridine orange/ethidium bromide (AO/EB) staining and DNA fragmentation assay. The binding affinity of withanolides in Viwithan with antiapoptotic proteins B-cell lymphoma 2, B-cell lymphoma-extra large, and myeloid cell leukemia 1 (MCL-1) were studied using in silico approach. Results: The half maximal inhibitory concentration (IC50) values of Viwithan against liver hepatocellular carcinoma, Henrietta Lacks cervical carcinoma cells, human colorectal carcinoma cell line, and Ehrlich ascites carcinoma cells were 1830, 968, 2715, and 633 μg/ml, respectively. Interestingly, Viwithan was highly effective against B16F1 cells with an IC50 value of 220 μg/ml after 24 h treatment. The morphological alterations of apoptotic cell death were clearly observed in the AO/EB-stained cells after treatment with Viwithan. Viwithan induced late apoptotic changes in treated B16F1 cells as evident by the ladder formation of fragmented DNA in a time-dependent manner. The findings of molecular docking showed that withanolides present in Viwithan have a more binding affinity with the antiapoptotic proteins, particularly MCL-1. Conclusion: We have reported for the first time that Viwithan with 5% withanolides has a potent cytotoxic effect, particularly against B16F1 murine melanoma cells among the different cancer cell lines tested. SUMMARY The present study reports for the first time that Viwithan, a standardized 5% Withania somnifera root extract, has potent cytotoxicity against B16F1 murine melanoma cellsWe have investigated the in vitro cytotoxicity of Viwithan in different human and murine cancer cells. Interestingly, we found that Viwithan was particularly very effective against B16F1 melanoma cells with a half maximal inhibitory concentration value of 220 μg/mlThe microscopic observations following acridine orange/ethidium bromide staining and DNA fragmentation assays clearly indicated that Viwithan might initiate late apoptosis in B16F1 cellsThe binding affinity of withanolides in Viwithan with antiapoptotic proteins of B-cell lymphoma 2 family was predicted using AutoDock tool. The results from in silico studies indicated a plausible synergistic effect of withanolides attributing to the Viwithan-induced apoptosis through suppression of intrinsic pathway for carcinogenesis. Abbreviations used: MTT: Thiazolyl blue tetrazolium blue; DMSO: Dimethyl sulfoxide; BSA: Bovine serum albumin; DMEM: Dulbecco's minimum essential medium; NCCS: National Centre for Cell Science; PBS: Phosphate-Buffered Saline; HepG2: Liver hepatocellular carcinoma; HeLa: Henrietta Lacks cervical carcinoma cells; HCT-116: Human colorectal carcinoma cell line; EAC: Ehrlich ascites carcinoma cells; IC50: Half maximal inhibitory concentration; AO/EB: Acridine orange/Ethidium bromide; BCL-2: B-cell lymphoma 2; BCL-XL: B-cell lymphoma-extra large; MCL-1: Myeloid cell leukemia 1; PDB: Protein Data Bank; ANOVA: Analysis of variance. PMID:29491636
Viwithan, a Standardized Withania somnifera Root Extract Induces Apoptosis in Murine Melanoma Cells.
Sudeep, H V; Gouthamchandra, K; Venkatesh, B J; Prasad, K Shyam
2018-01-01
Withania somnifera is an Indian medicinal herb known for the multipotential ability to cure various therapeutic ailments as described in the ayurvedic system of medicine. In the present study, we have evaluated the antiproliferative activity of a standardized W. somnifera root extract (Viwithan) against different human and murine cancer cell lines. The cytotoxicity of Viwithan was determined using thiazolyl blue tetrazolium blue assay and crystal violet staining. The apoptotic changes in B16F1 cells following treatment with Viwithan were observed by acridine orange/ethidium bromide (AO/EB) staining and DNA fragmentation assay. The binding affinity of withanolides in Viwithan with antiapoptotic proteins B-cell lymphoma 2, B-cell lymphoma-extra large, and myeloid cell leukemia 1 (MCL-1) were studied using in silico approach. The half maximal inhibitory concentration (IC50) values of Viwithan against liver hepatocellular carcinoma, Henrietta Lacks cervical carcinoma cells, human colorectal carcinoma cell line, and Ehrlich ascites carcinoma cells were 1830, 968, 2715, and 633 μg/ml, respectively. Interestingly, Viwithan was highly effective against B16F1 cells with an IC50 value of 220 μg/ml after 24 h treatment. The morphological alterations of apoptotic cell death were clearly observed in the AO/EB-stained cells after treatment with Viwithan. Viwithan induced late apoptotic changes in treated B16F1 cells as evident by the ladder formation of fragmented DNA in a time-dependent manner. The findings of molecular docking showed that withanolides present in Viwithan have a more binding affinity with the antiapoptotic proteins, particularly MCL-1. We have reported for the first time that Viwithan with 5% withanolides has a potent cytotoxic effect, particularly against B16F1 murine melanoma cells among the different cancer cell lines tested. The present study reports for the first time that Viwithan, a standardized 5% Withania somnifera root extract, has potent cytotoxicity against B16F1 murine melanoma cellsWe have investigated the in vitro cytotoxicity of Viwithan in different human and murine cancer cells. Interestingly, we found that Viwithan was particularly very effective against B16F1 melanoma cells with a half maximal inhibitory concentration value of 220 μg/mlThe microscopic observations following acridine orange/ethidium bromide staining and DNA fragmentation assays clearly indicated that Viwithan might initiate late apoptosis in B16F1 cellsThe binding affinity of withanolides in Viwithan with antiapoptotic proteins of B-cell lymphoma 2 family was predicted using AutoDock tool. The results from in silico studies indicated a plausible synergistic effect of withanolides attributing to the Viwithan-induced apoptosis through suppression of intrinsic pathway for carcinogenesis. Abbreviations used: MTT: Thiazolyl blue tetrazolium blue; DMSO: Dimethyl sulfoxide; BSA: Bovine serum albumin; DMEM: Dulbecco's minimum essential medium; NCCS: National Centre for Cell Science; PBS: Phosphate-Buffered Saline; HepG2: Liver hepatocellular carcinoma; HeLa: Henrietta Lacks cervical carcinoma cells; HCT-116: Human colorectal carcinoma cell line; EAC: Ehrlich ascites carcinoma cells; IC50: Half maximal inhibitory concentration; AO/EB: Acridine orange/Ethidium bromide; BCL-2: B-cell lymphoma 2; BCL-XL: B-cell lymphoma-extra large; MCL-1: Myeloid cell leukemia 1; PDB: Protein Data Bank; ANOVA: Analysis of variance.
STS-26 MS Nelson operates controls for PVTOS-2 experiment on aft middeck
NASA Technical Reports Server (NTRS)
1988-01-01
STS-26 Mission Specialist (MS) George D. Nelson operates generic electronics module for the Physical Vapor Transport of Organic Solids 2 (PVTOS-2) experiment on Discovery's, Orbiter Vehicle (OV) 103's, aft middeck. PVTOS-2 consists of nine independent experimental cells about 12 inches long and 3 inches in diameter. They are mounted in a circular base plate inside the drum-like experimental apparatus container (EAC). PVTOS-2 is sponsored by NASA's Office of Commercial Programs and is being conducted by 3M's Space Research and Applications Laboratory.
NASA Astrophysics Data System (ADS)
Raut, Subhajit; Babu, P. D.; Sharma, R. K.; Pattanayak, Ranjit; Panigrahi, Simanchalo
2018-05-01
We investigated the anomalous behaviour in the dielectric properties, occurring nearly at room temperature and at elevated temperatures (near the Neel temperature TN) of the polycrystalline samples of YFeO3 (YFO) ceramics. On the prepared YFO ceramics, the magnetic measurements showed the Neel temperature of YFO to be 650 K, below which the compound exhibited the weak ferromagnetic behaviour. X-ray photoelectron spectroscopy (XPS) shows the presence of Fe ions (Fe2+ and Fe3+ states) and also revealed the formation of the oxygen vacancies. The frequency dependence of the complex dielectric constant within the frequency domain of 100 Hz-1 MHz shows the presence of grain dominated dielectric relaxation over the thermal window of 300-373 K. The activation energy Eact.ɛ=0.611 eV extracted from the imaginary permittivity spectrum indicates the involvement of oxygen vacancies in the relaxation process. Above 493 K, the ac conductivity, complex impedance, and modulus studies revealed appreciable conduction and relaxation processes occurring in YFO ceramics with respective activation energies Eac t . σ=1.362 eV and Eac t . Z=1.345 eV , which suggests that the oxygen vacancies are also involved for the anomalous behaviour of the dielectric constant at elevated temperatures. The temperature dependent Raman spectroscopic measurements within the thermal window of 298-698 K showed anomalous variations of the line widths and frequencies of several Raman active modes above 473 K up to the vicinity of TN pointing towards the presence of admixtures of the electron-phonon and spin-phonon coupling in the system. A further study on the thermal variation of the B2g(4) mode frequency with [M(T)/MS]2 shows the occurrence of strong spin-phonon (s-p) coupling, while the line shape shows the presence of the Fano asymmetry, suggesting spin dependent electron-phonon (e-p) coupling in the system below TN.
Magnetic Design Guidelines for Electronic Power Supplies.
1986-09-30
henries ",= peak flux density in gauss d = wire (conductor) dia in mils CM = d2 = circular mi’s Irms = RMS current in amperes Idc = DC current in...component lac = RMS ac current in the inductor f = minimum frequency in hertz L = inductance in henries Then Eac 2 16.83 x 2, x 760 x .05 10 Eac 1 168.3 x 2...duty cycle x 1/f L inductance in henries *permeability in gauss/oersted H magnetizing force in oersteds ’. i g length of air gap in cm ic length of
Effect of hypolipidemic drugs on basal and stimulated adenylate cyclase activity in tumor cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bershtein, L.M.; Kovaleva, I.G.; Rozenberg, O.A.
1986-02-01
This paper studies adenylate cyclase acticvity in Ehrlich's ascites carcinoma (EAC) cells during administration of drugs with a hypolipidemic action. Seven to eight days before they were killed, male mice ingested the antidiabetic biguanide phenformin, and the phospholipid-containing preparation Essentiale in drinking water. The cAMP formed was isolated by chromatography on Silufol plates after incubation of the enzyme preparation with tritium-ATP, or was determined by the competitive binding method with protein. It is shown that despite the possible differences in the concrete mechanism of action of the hypolipidemic agents chosen for study on the cyclase system, the use of suchmore » agents, offers definite prospects for oriented modification of the hormone sensitivity of tumor cells.« less
Huang, Chun-Jung; Webb, Heather E; Beasley, Kathleen N; McAlpine, David A; Tangsilsat, Supatchara E; Acevedo, Edmund O
2014-03-01
Pentraxin 3 (PTX3) has been recently identified as a biomarker of vascular inflammation in predicting cardiovascular events. The purpose of this study was to examine the effect of cardiorespiratory fitness on plasma PTX3 and cortisol responses to stress, utilizing a dual-stress model. Fourteen male subjects were classified into high-fit (HF) and low-fit (LF) groups and completed 2 counterbalanced experimental conditions. The exercise-alone condition (EAC) consisted of cycling at 60% maximal oxygen uptake for 37 min, while the dual-stress condition (DSC) included 20 min of a mental stress while cycling for 37 min. Plasma PTX3 revealed significant increases over time with a significant elevation at 37 min in both HF and LF groups in response to EAC and DSC. No difference in plasma PTX3 levels was observed between EAC and DSC. In addition, plasma cortisol revealed a significant condition by time interaction with greater levels during DSC at 37 min, whereas cardiorespiratory fitness level did not reveal different plasma cortisol responses in either the EAC or DSC. Aerobic exercise induces plasma PTX3 release, while additional acute mental stress, in a dual-stress condition, does not exacerbate or further modulate the PTX3 response. Furthermore, cardiorespiratory fitness may not affect the stress reactivity of plasma PTX3 to physical and combined physical and psychological stressors. Finally, the exacerbated cortisol responses to combined stress may provide the potential link to biological pathways that explain changes in physiological homeostasis that may be associated with an increase in the risk of cardiovascular disease.
Sex and Gender Differences in Gastroesophageal Reflux Disease
Kim, Young Sun; Kim, Nayoung; Kim, Gwang Ha
2016-01-01
It is important to understand sex and gender-related differences in gastroesophageal reflux disease (GERD) because gender-related biologic factors might lead to better prevention and therapy. Non-erosive reflux disease (NERD) affects more women than men. GERD symptoms are more frequent in patients with NERD than in those with reflux esophagitis. However, men suffer pathologic diseases such as reflux esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) more frequently than women. The prevalence of reflux esophagitis is significantly increased with age in women, especially after their 50s. The mean age of EAC incidence in women is higher than in men, suggesting a role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux esophagitis model, nitric oxide was found to be an aggravating factor of esophageal injury in a male-predominant way. In addition, the expression of esophageal occludin, a tight junction protein that plays an important role in the esophageal defense mechanism, was up-regulated in women. This explains the male predominance of reflux esophagitis and delayed incidence of BE or EAC in women. Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal symptoms have been more frequently reported by women than by men, suggesting that sex and gender play a role in symptom perception. Differential sensitivity with augmented symptoms in women might have diagnostic and therapeutic influence. Furthermore, recent studies have suggested that hormone replacement therapy has a protective effect against esophageal cancer. However, an anti-inflammatory role of estrogen remains compelling, which means further study is necessary in this area. PMID:27703114
Book, J.W.; Signell, R.P.; Perkins, H.
2007-01-01
Fifteen bottom-mounted Acoustic Doppler Current Profilers were deployed from October 2002 through April 2003 in the northern Adriatic Sea. Average transport from the portion of the Western Adriatic Current (WAC) along the Italian slope was 0.1470 ?? 0.0043 Sv, punctuated by bursts of more than twice that amount during storm events. Monthly means were calculated with times of strong wind-driven circulation excluded. These suggest a 2002/2003 seasonal separation consisting of October, December through February, and March through April. An extreme Po River flood influenced November conditions making seasonal categorization difficult. October generally had more kinetic energy and more vertical structure than other months, and near-inertial waves were more frequent in April and October. The Eastern Adriatic Current (EAC)/WAC (i.e. inflow/outflow) system was clearly present in the means for all months. The cyclonic gyre north of the Po River was present October through February. Generally, in the WAC, over 50% of kinetic energy came from vertically uniform monthly mean flows. Elsewhere, eddy kinetic energy was stronger than mean kinetic energy with 10-40% contributions for vertically uniform monthly mean flows, 40-60% for vertically uniform monthly varying flows, and 10-30% for vertically varying monthly varying flows. Mean currents for bora storms indicate enhancement of the EAC/WAC and the cyclonic northern gyre, a shift toward Kvarner Bay in EAC direction, a circulation null point south of the Po, and double-gyre bifurcation of flow at Istria. Strengthening of both the EAC and WAC also occurs during sirocco storms. Copyright 2007 by the American Geophysical Union.
NASA Astrophysics Data System (ADS)
Schaeffer, A.; Roughan, M.; Wood, J. E.
2014-08-01
Western boundary currents strongly influence the dynamics on the adjacent continental shelf and in particular the cross-shelf transport and uplift through the bottom boundary layer. Four years of moored in situ observations on the narrow southeastern Australian shelf (in water depths of between 65 and 140 m) were used to investigate bottom cross-shelf transport, both upstream (30°S) and downstream (34°S) of the separation zone of the East Australian Current (EAC). Bottom transport was estimated and assessed against Ekman theory, showing consistent results for a number of different formulations of the boundary layer thickness. Net bottom cross-shelf transport was onshore at all locations. Ekman theory indicates that up to 64% of the transport variability is driven by the along-shelf bottom stress. Onshore transport in the bottom boundary layer was more intense and frequent upstream than downstream, occurring 64% of the time at 30°S. Wind-driven surface Ekman transport estimates did not balance the bottom cross-shelf flow. At both locations, strong variability was found in bottom water transport at periods of approximately 90-100 days. This corresponds with periodicity in EAC fluctuations and eddy shedding as evidenced from altimeter observations, highlighting the EAC as a driver of variability in the continental shelf waters. Ocean glider and HF radar observations were used to identify the bio-physical response to an EAC encroachment event, resulting in a strong onshore bottom flow, the uplift of cold slope water, and elevated coastal chlorophyll concentrations.
Development of an expert system for fractography of environmentally assisted cracking
DOE Office of Scientific and Technical Information (OSTI.GOV)
Minoshima, Kohji; Komai, Kenjiro; Yamasaki, Norimasa
1997-12-31
An expert system that diagnoses the causes of failure of environmentally assisted cracking (EAC) based upon fractography has been developed. The system uses the OPS83 programming language, expressing rules in the manner of production rules, and is composed of three independent subsystems, which respectively deal with EACs of high-strength or high-tensile-strength steel, aluminum alloy, and stainless steel in dry and humidified air, water, and aqueous solutions containing Cl, Br, or I ions. The concerned EAC issues cover stress corrosion cracking (SCC), hydrogen embrittlement, cyclic SCC, dynamic SCC, and corrosion fatigue as well as fatigue and overload fracture. The knowledge basemore » covers the rules relating to not only environments, materials, and loading conditions, but also macroscopic and microscopic fracture surface morphology. In order to deal with vague expressions of fracture surface morphology, fuzzy set theory is used in the system, and the description of rules about vague fracture surface appearance is thereby possible. Applying the developed expert system to case histories, accurate diagnoses were made. The authors discuss the related diagnosis results and usefulness of the developed system.« less
Kumar, Harish; Savaliya, Mihir; Biswas, Subhankar; Nayak, Pawan G; Maliyakkal, Naseer; Manjunath Setty, M; Gourishetti, Karthik; Pai, K Sreedhara Ranganath
2016-08-01
Various parts of Mimusops elengi Linn. (Sapotaceae) have been used widely in traditional Indian medicine for the treatment of pain, inflammation and wounds. The study was conducted to explore the use of stem bark of M. elengi on pharmacological grounds and to evaluate the scientific basis of cytotoxic and anti-tumor activity. Extract/fractions were prepared and in vitro cytotoxicity was assessed using SRB assay. Most effective fractions were subjected to fluorescence microscopy based acridine orange/ethidium bromide (AO/EB) and Hoechst 33342 staining to determine apoptosis induction and DNA fragmentation assay. Comet and micronuclei assay were performed to assess genotoxicity. Cell cycle analysis was also performed. In vivo anti-tumor potential was evaluated by Ehrlich ascites carcinoma (EAC) model in mice. The alcoholic stem bark extract of M. elengi along with four fractions showed potential in vitro cytotoxicity in SRB assay. Of these, dichloromethane and ethyl acetate fractions were selected for further studies. The fractions revealed apoptosis inducing potential in AO/EB and Hoechst 33342 staining, which was further confirmed by DNA fragmentation assay. Genotoxic potential was revealed by comet and micronuclei assay. Fractions also exhibited specific cell cycle inhibition in G0/G1 phase. In EAC model, ethyl acetate fraction along with the standard (cisplatin) effectively reduced the increase in body weight compared to control and improved mean survival time. Both fractions were able to restore the altered hematological and biochemical parameters. Hence, M. elengi stem bark may be a possible therapeutic candidate having cytotoxic and anti-tumor potential.
Dedja, Arben; Giacometti, Cinzia; Francia, Simona; Fabris, Federico; Zaramella, Alice; Gallagher, Emily J.; Cassaro, Mauro; Rugge, Massimo; LeRoith, Derek; Alberti, Alfredo; Realdon, Stefano
2018-01-01
Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett’s Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side—to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis. PMID:29662006
Arcidiacono, Diletta; Dedja, Arben; Giacometti, Cinzia; Fassan, Matteo; Nucci, Daniele; Francia, Simona; Fabris, Federico; Zaramella, Alice; Gallagher, Emily J; Cassaro, Mauro; Rugge, Massimo; LeRoith, Derek; Alberti, Alfredo; Realdon, Stefano
2018-04-14
Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett's Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side-to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.
Quantitative ultrasound imaging for monitoring in situ high-intensity focused ultrasound exposure.
Ghoshal, Goutam; Kemmerer, Jeremy P; Karunakaran, Chandra; Abuhabsah, Rami; Miller, Rita J; Sarwate, Sandhya; Oelze, Michael L
2014-10-01
Quantitative ultrasound (QUS) imaging is hypothesized to map temperature elevations induced in tissue with high spatial and temporal resolution. To test this hypothesis, QUS techniques were examined to monitor high-intensity focused ultrasound (HIFU) exposure of tissue. In situ experiments were conducted on mammary adenocarcinoma tumors grown in rats and lesions were formed using a HIFU system. A thermocouple was inserted into the tumor to provide estimates of temperature at one location. Backscattered time-domain waveforms from the tissue during exposure were recorded using a clinical ultrasonic imaging system. Backscatter coefficients were estimated using a reference phantom technique. Two parameters were estimated from the backscatter coefficient (effective scatterer diameter (ESD) and effective acoustic concentration (EAC). The changes in the average parameters in the regions corresponding to the HIFU focus over time were correlated to the temperature readings from the thermocouple. The changes in the EAC parameter were consistently correlated to temperature during both heating and cooling of the tumors. The changes in the ESD did not have a consistent trend with temperature. The mean ESD and EAC before exposure were 120 ± 16 μm and 32 ± 3 dB/cm3, respectively, and changed to 144 ± 9 μm and 51 ± 7 dB/cm3, respectively, just before the last HIFU pulse was delivered to the tissue. After the tissue cooled down to 37 °C, the mean ESD and EAC were 126 ± 8 μm and 35 ± 4 dB/cm3, respectively. Peak temperature in the range of 50-60 °C was recorded by a thermocouple placed just behind the tumor. These results suggest that QUS techniques have the potential to be used for non-invasive monitoring of HIFU exposure. © The Author(s) 2014.
Humphreys, Jennifer H; van Nies, Jessica A B; Chipping, Jackie; Marshall, Tarnya; van der Helm-van Mil, Annette H M; Symmons, Deborah P M; Verstappen, Suzanne M M
2014-12-04
This study aimed to investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA). Data from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment. A total of 4962 patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. In NOAR and EAC respectively, 35% and 42% of patients were ACPA/RF positive. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% confidence interval) 1.35 (1.09 to 1.68) and 1.58 (1.16 to 2.15). Patients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality.
Ray, A F; Peirce, S C; Wilkes, A R; Carolan-Rees, G
2015-10-01
In prelabour rupture of membranes (PROM) or preterm PROM the amniotic membranes rupture prior to labour. Where this is not overt a speculum examination is undertaken to confirm diagnosis. The Vision Amniotic Leak Detector (ALD) is a panty liner that can diagnose amniotic fluid as a cause of vaginal wetness. It was evaluated by the UK National Institute for Health and Care Excellence (NICE) as part of the Medical Technologies Evaluation Programme. The sponsor (CommonSense Ltd) identified five studies, of which three were deemed within scope by the External Assessment Centre (EAC). Two of these three used an inappropriate comparator. The EAC recalculated the diagnostic accuracy of Vision ALD using speculum examination as the comparator: sensitivity of 97% (95% CI 93-99%), negative predictive value of 96% (95% CI 92-98%). A negative result would therefore allow patients to be discharged with confidence. In the sponsor's cost-consequence model only patients with a positive Vision ALD result would have a speculum examination, producing a cost saving of around £10 per patient. The EAC felt that some costs were unjustified and the model did not include infection outcomes or use in a community setting. The EAC revised the sponsor's model and found the results were most sensitive to clinician costs. Vision ALD was associated with savings of around £15-£25 per patient when administration in lower-cost community healthcare avoided a referral to a higher-cost secondary-care centre. NICE published guidance MTG15 in July 2013 recommending that the case for adopting Vision ALD was supported by the evidence.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Villeneuve, Daniel L.; Blake, Lindsey S.; Brodin, Jeffrey
2007-08-01
This study evaluated changes in the expression of steroidogenesis-related genes in male fathead minnows exposed to ketoconazole (KTC) or vinclozolin (VZ) for 21 days. The aim was to evaluate links between molecular changes and higher level outcomes after exposure to endocrine-active chemicals (EACs) with different modes of action. To aid our analysis and interpretation of EAC-related effects, we first examined variation in the relative abundance of steroidogenesis-related gene transcripts in the gonads of male and female fathead minnows as a function of age, gonad development, and spawning status, independent of EAC exposure. Gonadal expression of several genes varied with agemore » and/or gonadal somatic index in either males or females. However, with the exception of aromatase, steroidogenesis-related gene expression did not vary with spawning status. Following the baseline experiments, expression of the selected genes in male fathead minnows exposed to KTC or VZ was evaluated in the context of effects observed at higher levels of organization. Exposure to KTC elicited changes in gene transcription that were consistent with an apparent compensatory response to the chemical's anticipated direct inhibition of steroidogenic enzyme activity. Exposure to VZ, an antiandrogen expected to indirectly impact steroidogenesis, increased pituitary expression of follicle-stimulating hormone beta-subunit as well as testis expression of 20beta-hydroxysteroid dehydrogenase and luteinizing hormone receptor transcripts. Results of this study contribute to ongoing research aimed at understanding responses of the teleost hypothalamic-pituitary-gonadal axis to different types of EACs and how changes in molecular endpoints translate into apical outcomes reflective of either adverse effect or compensation.« less
Risk of recurrence of Barrett's esophagus after successful endoscopic therapy
Krishnamoorthi, Rajesh; Singh, Siddharth; Ragunathan, Karthik; Katzka, David A.; Wang, Kenneth K.; Iyer, Prasad G.
2016-01-01
Background and Aims Previous estimates of incidence of intestinal metaplasia (IM) recurrence after achieving complete remission of IM (CRIM) through endoscopic therapy of Barrett's esophagus (BE) have varied widely. We performed a systematic review and meta-analysis of studies to estimate an accurate recurrence risk after CRIM. Methods We performed a systematic search of multiple literature databases through June 2015 to identify studies reporting long-term follow-up after achieving CRIM through endoscopic therapy. Pooled incidence rate (IR) of recurrent IM, dysplastic BE, and high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) per person-year of follow-up after CRIM was estimated. Factors associated with recurrence were also assessed. Results We identified 41 studies that reported 795 cases of recurrence in 4443 patients over 10,427 patient-years of follow-up. This included 21 radiofrequency ablation studies that reported 603 cases of IM recurrence in 3186 patients over 5741 patient-years of follow-up. Pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC after radiofrequency ablation were 9.5% (95% CI, 6.7-12.3), 2.0% (95% CI, 1.3-2.7), and 1.2% (95% CI, .8-1.6) per patient-year, respectively. When all endoscopic modalities were included, pooled IRs of recurrent IM, dysplastic BE, and HGD/EAC were 7.1% (95% CI, 5.6-8.6), 1.3% (95% CI, .8-1.7), and .8% (95% CI, .5-1.1) per patient-year, respectively. Substantial heterogeneity was noted. Increasing age and BE length were predictive of recurrence; 97% of recurrences were treated endoscopically. Conclusions The incidence of recurrence after achieving CRIM through endoscopic therapy was substantial. A small minority of recurrences were dysplastic BE and HGD/EAC. Hence, continued surveillance after CRIM is imperative. Additional studies with long-term follow-up are needed. PMID:26902843
Short-term complementary and alternative medicine on quality of life in women with fibromyalgia.
Dias, Paulo Araujo; Guimarães, André Brito Bastos; Albuquerque, Andrea de Oliveira; de Oliveira, Karoline Lucas; Cavalcante, Maria Luzete Costa; Guimarães, Sergio Botelho
2016-01-01
Fibromyalgia (FMS) is a syndrome characterized by chronic widespread musculoskeletal pain, whose etiology is not completely understood. Different therapeutic approaches have been used with inconsistent results. This observation does not invalidate the continued search for alternative treatments aimed at improving quality of life (QoL) in FMS. This study compared three classical traditional Chinese medicine (TCM) therapies: acupuncture (AC), electroacupuncture (EAC) and moxibustion (MX) in the management of pain and promotion of QoL in FMS patients. A preliminary, group-assigned, comparative study enrolled 30 women, mean age (46.90±9.24) years (range 20-60 years), who met the 1990 American College of Rheumatology criteria for FMS diagnosis and a pain-pressure threshold (PPT) < 4 kg/cm(2). The study was conducted in a teaching tertiary-care medical institution from May 2010 through April 2012. AC, EAC and MX were delivered for 30 min, once a week, for 8 weeks, bilaterally at Neiguan (PC6), Hegu (LI4), Yanglingquan (GB34), Sanyinjiao (SP6) and Taichong (LR3) acupoints. Each week, immediately before treatment and after treatment, subjects were tested for PPTs, Wong-Baker Faces Pain Scale (WBFPS; for pain intensity) and Medical Outcomes Study 36-item Short Form Health Survey (SF-36: for QoL). There was no significant improvement in pain or reduction of tender points in any of the groups studied, at the end of the 8th session. Significant improvement of QoL was perceived in vitality (after AC treatment) and in mental health (after EAC and MX treatments). TCM therapies (AC, EAC and MX) promoted an improvement in the QoL in two areas (vitality and mental health) in FMS women. Further large-scale clinical trials are required to confirm this effect.
Gaddam, Srinivas; Singh, Mandeep; Balasubramanian, Gokulakrishnan; Thota, Prashanthi; Gupta, Neil; Wani, Sachin; Higbee, April D; Mathur, Sharad C; Horwhat, John D; Rastogi, Amit; Young, Patrick E; Cash, Brooks D; Bansal, Ajay; Vargo, John J; Falk, Gary W; Lieberman, David A; Sampliner, Richard E; Sharma, Prateek
2013-09-01
Recent population-based studies have shown a low risk of esophageal adenocarcinoma (EAC) in patients with nondysplastic Barrett's esophagus (NDBE). We evaluated whether persistence of NDBE over multiple consecutive surveillance endoscopic examinations could be used in risk stratification of patients with Barrett's esophagus (BE). We performed a multicenter outcomes study of a large cohort of patients with BE. Based on the number of consecutive surveillance endoscopies showing NDBE, we identified 5 groups of patients. Patients in group 1 were found to have NDBE at their first esophagogastroduodenoscopy (EGD). Patients in group 2 were found to have NDBE on their first 2 consecutive EGDs. Similarly, patients in groups 3, 4, and 5 were found to have NDBE on 3, 4, and 5 consecutive surveillance EGDs. A logistic regression model was built to determine whether persistence of NDBE independently protected against development of cancer. Of a total of 3515 patients with BE, 1401 patients met the inclusion criteria (93.3% white; 87.5% men; median age, 60 ±17 years). The median follow-up period was 5 ± 3.9 years (7846 patient-years). The annual risk of EAC in groups 1 to 5 was 0.32%, 0.27%, 0.16%, 0.2%, and 0.11%, respectively (P for trend = .03). After adjusting for age, sex, and length of BE, persistence of NDBE, based on multiple surveillance endoscopies, was associated with a gradually lower likelihood of progression to EAC. Persistence of NDBE over several endoscopic examinations identifies patients who are at low risk for development of EAC. These findings support lengthening surveillance intervals or discontinuing surveillance of patients with persistent NDBE. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
Ong, Chin-Ann J.; Shapiro, Joel; Nason, Katie S.; Davison, Jon M.; Liu, Xinxue; Ross-Innes, Caryn; O'Donovan, Maria; Dinjens, Winand N.M.; Biermann, Katharina; Shannon, Nicholas; Worster, Susannah; Schulz, Laura K.E.; Luketich, James D.; Wijnhoven, Bas P.L.; Hardwick, Richard H.; Fitzgerald, Rebecca C.
2013-01-01
Purpose Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. Patients and Methods We recently identified eight molecular prognostic biomarkers using two different genomic platforms. IHC scores of these biomarkers from a UK multicenter cohort (N = 374) were used in univariate Cox regression analysis to determine the smallest biomarker panel with the greatest prognostic power with potential therapeutic relevance. This new panel was validated in two independent cohorts of patients with EAC who had undergone curative esophagectomy from the United States and Europe (N = 666). Results Three of the eight previously identified prognostic molecular biomarkers (epidermal growth factor receptor [EGFR], tripartite motif-containing 44 [TRIM44], and sirtuin 2 [SIRT2]) had the strongest correlation with long-term survival in patients with EAC. Applying these three biomarkers as an IHC panel to the validation cohort segregated patients into two different prognostic groups (P < .01). Adjusting for known survival covariates, including clinical staging criteria, the IHC panel remained an independent predictor, with incremental adverse overall survival (OS) for each positive biomarker (hazard ratio, 1.20; 95% CI, 1.03 to 1.40 per biomarker; P = .02). Conclusion We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage. PMID:23509313
NASA Astrophysics Data System (ADS)
Roughan, M.
2016-02-01
The East Australian Current (EAC) flows as a jet over the narrow shelf of southeastern Australia, dominating shelf circulation, and shedding vast eddies at the highly variable separation point. These characteristics alone make it a dynamically challenging region to measure, model and predict. In recent years a significant effort has been placed on understanding continental shelf processes along the coast of SE Australia, adjacent to the EAC, our major Western Boundary Current. We have used a multi-pronged approach by combining state of the art in situ observations and data assimilation modelling. Observations are obtained from a network of moorings, HF Radar and ocean gliders deployed in shelf waters along SE Australia, made possible through Australia's Integrated Marine Observing System (IMOS). In addition, we have developed a high resolution reanalysis of the East Australian Current using ROMS and 4DVar data Assimilation. In addition to the traditional data streams (SST, SSH and ARGO) we assimilate the newly available IMOS observations in the region. These include velocity and hydrographic observations from the EAC transport array, 1km HF radar measurements of surface currents, CTD casts from ocean gliders, and temperature, salinity and velocity measurements from a network of shelf mooring arrays. We use these vast data sets and numerical modelling tools combined with satellite remote sensed data to understand spatio-temporal variability of shelf processes and water mass distributions on synoptic, seasonal and inter-annual timescales. We have quantified the cross shelf transport variability inshore of the EAC, the driving mechanisms, the seasonal cycles in shelf waters and to some extent variability in the biological (phytoplankton) response. I will present a review of some of the key results from a number of recent studies.
Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid.
Ojima, Eisuke; Fujimura, Takashi; Oyama, Katsunobu; Tsukada, Tomoya; Kinoshita, Jun; Miyashita, Tomoharu; Tajima, Hidehiro; Fushida, Sachio; Harada, Shin-ichi; Mukaisho, Ken-ichi; Hattori, Takanori; Ohta, Tetsuo
2015-08-01
Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation-metaplasia-carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p < 0.05) than in the control group, and EAC was not observed (p < 0.05). In analysis of the compartment of bile acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p < 0.05) and cholic acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p < 0.05). Expression intensity of Cdx2 and NF-κB was greater in the control group than in the UDCA group (p < 0.05). UDCA may be a chemopreventive agent against EAC by varying the bile acid composition.
Ryom, L; Boesecke, C; Gisler, V; Manzardo, C; Rockstroh, J K; Puoti, M; Furrer, H; Miro, J M; Gatell, J M; Pozniak, A; Behrens, G; Battegay, M; Lundgren, J D
2016-02-01
The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview. © 2015 British HIV Association.
Nasir, Hina; Javaid, Nadeem; Sher, Muhammad; Qasim, Umar; Khan, Zahoor Ali; Alrajeh, Nabil; Niaz, Iftikhar Azim
2016-01-01
This paper embeds a bi-fold contribution for Underwater Wireless Sensor Networks (UWSNs); performance analysis of incremental relaying in terms of outage and error probability, and based on the analysis proposition of two new cooperative routing protocols. Subject to the first contribution, a three step procedure is carried out; a system model is presented, the number of available relays are determined, and based on cooperative incremental retransmission methodology, closed-form expressions for outage and error probability are derived. Subject to the second contribution, Adaptive Cooperation in Energy (ACE) efficient depth based routing and Enhanced-ACE (E-ACE) are presented. In the proposed model, feedback mechanism indicates success or failure of data transmission. If direct transmission is successful, there is no need for relaying by cooperative relay nodes. In case of failure, all the available relays retransmit the data one by one till the desired signal quality is achieved at destination. Simulation results show that the ACE and E-ACE significantly improves network performance, i.e., throughput, when compared with other incremental relaying protocols like Cooperative Automatic Repeat reQuest (CARQ). E-ACE and ACE achieve 69% and 63% more throughput respectively as compared to CARQ in hard underwater environment. PMID:27420061
Congenital aural atresia and stenosis: surgery strategies and long-term results.
Li, Chenlong; Zhang, Tianyu; Fu, Yaoyao; Qing, Fenghua; Chi, Fanglu
2014-07-01
To compare the patients who underwent surgery for congenital aural atresia (CAA) with congenital aural stenosis (CAS) for the stability of hearing results and complications during long-term follow-up. Retrospective review. Seventy-five CAA patients and fifty CAS patients who underwent congenital meatoplasty with canalplasty and tympanoplasty between 2007 and 2012. Paired comparison analyses detected no significant difference in preoperative ABG but significant changes in postoperative ABG, ΔABG, the number of ABG < 30 dB and ABG < 10 dB between CAA and CAS. Complications such as postoperative stenosis, bony regrowth, external aural canal (EAC) infection, EAC eczema, total deaf, and lateralization of the tympanic membrane (TM) were observed in 61.3% of patients with CAA and 20% of patients with CAS. Chi square test detected significant differences in complications between patients with CAA and CAS (χ(2) = 20.73, p < 0.01). Meatoplasty with canalplasty and tympanoplasty in individuals with CAS can yield reliable and lasting positive hearing results with a low incidence of severe complications. The existence and preoperative condition of patients' TM and EAC skin helped improve hearing results and decrease the incidence of complications. However, the final hearing results and complications required stricter indications for CAA patients.
NASA Astrophysics Data System (ADS)
Writer, J.; Keefe, S.; Barber, L. B.; Brown, G.; Schoenfuss, H.; Kiesling, R.; Gray, J. L.
2009-12-01
Select endocrine active compounds (EACs) were measured in four rivers in southern Minnesota. Additionally, caged and wild fish were assessed for indication of endocrine disruption using plasma vitellogenin and histopathology. Low concentrations of EACs were identified in all rivers, as was elevated plasma vitellogenin in caged and wild fish, indicating potential endocrine disruption. To evaluate the persistence of these compounds in small rivers, a tracer study was performed on one of the rivers (Redwood River) using Lagrangian sampling coupled with hydrologic modeling incorporating transient storage. Mass exchange (transient storage, sorption) and degradation were approximated as pseudo first order processes, and in-stream removal rates were then computed by comparing conservative tracer concentrations to organic compound concentrations. Production of estrone and 4-nonylphenol in the studied reach as a result of biochemical transformation from their parent compounds (17β-estradiol and alkylphenolpolyethoxylates, respectively) was quantified. The distance required for 17β-estradiol and nonylphenol to undergo a 50% reduction in concentration was >2 km and >10 km, respectively. These results indicate that EACs are transported several kilometers downstream from discharge sources and therefore have the potential of adversely impacting the lotic ecosystem over these distances.
Equal-area criterion in power systems revisited
NASA Astrophysics Data System (ADS)
Sun, Yong; Ma, Jinpeng; Kurths, Jürgen; Zhan, Meng
2018-02-01
The classic equal-area criterion (EAC) is of key importance in power system analysis, and provides a powerful, pictorial and quantitative means of analysing transient stability (i.e. the system's ability to maintain stable operation when subjected to a large disturbance). Based on the traditional EAC, it is common sense in engineering that there is a critical cleaning time (CCT); namely, a power system is stable (unstable) if a fault is cleared before (after) this CCT. We regard this form of CCT as bipartite. In this paper, we revisit the EAC theory and, surprisingly, find different kinds of transient stability behaviour. Based on these analyses, we discover that the bipartite CCT is only one type among four major types, and, actually, the forms of CCT can be diversified. In particular, under some circumstances, a system may have no CCT or show a periodic CCT. Our theoretical analysis is verified by numerical simulations in a single-machine-infinite-bus system and also in multi-machine systems. Thus, our study provides a panoramic framework for diverse transient stability behaviour in power systems and also may have a significant impact on applications of multi-stability in various other systems, such as neuroscience, climatology or photonics.
PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease.
Ray, Tanusree; Pal, Amit
2016-05-01
Bacterial toxins have emerged as promising agents in cancer treatment strategy. Hemagglutinin (HAP) protease secreted by Vibrio cholerae induced apoptosis in breast cancer cells and regresses tumor growth in mice model. The success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity for normal tissues. Increased expression of Protease Activated Receptor-1 (PAR-1) has been reported in different malignant cells. In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50-p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same environment makes it a good therapeutic agent for treatment of cancer.
NASA Astrophysics Data System (ADS)
Agethen, Svenja; Wolff, Franziska; Knorr, Klaus-Holger
2016-04-01
Restoration of cut over peatlands in Central Europe is challenging in a landscape overused for agriculture. Excess nutrient availability by excess fertilization triggers uncharacteristic vegetation that is one key driver for carbon cycling. Those nutrient rich systems are often dominated by graminoids, and were often found to emit substantial amounts of methane. Plants grown under nutrient rich conditions provide more labile carbon in rhizodeposition and litter that fuels methanogenesis. Such species often have aerenchyma that facilitates direct CH4 emissions to the atmosphere and therefore impair the climate cooling function of bogs. On the other hand, aerenchymatic tissue supplies oxygen to the rhizosphere, which may reduce methanogenesis or stimulate methane oxidation, as methanogenesis is a strictly anaerobic process. Which of the effects prevail is often unclear. Therefore, the aim of this study was to test the impact of different vegetation on rhizospheric redox conditions and methanogenesis, including aerenchymatic vascular plants that are dominant in restored cut over peatlands. As ombrotrophic peat is poor in inorganic electron acceptors (EAs) to suppress methanogenesis, we analyzed the electron acceptor (EACs) and electron donor capacities (EDCs) of dissolved organic matter (DOM) in the rhizosphere to understand the impact of vegetation on anaerobic organic matter degradation. We planted Juncus effusus, Eriophorum vaginatum, Eriophorum angustifolium, Sphagnum (mixture of S. magellanicum, S. papillosum, S. sec. acutifolia, 1/3 each) plus non-vegetated controls; six replicates per batch; in containers with untreated homogenized peat. The plants grow under constant conditions (20° C, 12h diurnal light cycles and 80% RH). Anoxic conditions were achieved by keeping the water table at +10 cm. For monitoring, the rhizosphere is equipped with suction and gas samplers. We measure dissolved CO2 and CH4 concentrations, inorganic EAs (NO3-, Fe(III), and SO42-) and organic EDCs and EACs via mediated electrochemical reduction/oxidation. We also characterize DOM with fluorescence spectroscopy and monitor the growth of above ground biomass as proxy for photosynthetic activity and potential DOM source. Preliminary results showed after initially equal magnitude of EACs and EDCs in all batches an increase in total electron exchange capacity (Σ EAC, EDC) four weeks later, but EACs increased significantly higher for rooted plants (fivefold vs. threefold in Sphagnum and controls). Subsequently, higher CH4 concentrations were found for Sphagnum and the controls. In our ongoing study we will also try to relate the effect of vegetation on rhizosphere redox conditions to root and shoot biomass and photosynthesis. First results indicate that oxidation of organic EAs occurs for all tested graminoid species. The analysis of EACs and EDCs in the rhizosphere of dominant species may improve our understanding under which conditions methane production and emission is stimulated or reduced by presence of vascular, aerenchymatic plants.
T-dependence of human B lymphocyte proliferative response to mitogens.
Brochier, J; Samarut, C; Gueho, J P; Revillard, J P
1976-01-01
Human peripheral blood and tonsil lymphocytes were fractionated on anti-Ig-coated Sephadex columns or by centrifugation after rosetting with native sheep erythrocytes. Both methods allowed the recovery of B and T-enriched populations the purity of which was checked by fluorescein-labelled anti-Ig serum, E and EAC rosette formation, and heterologous antisera specific for B or T lymphocytes. The proliferative response of T cells to PHA, Con A, PWM, and ALS was not found different from that of unfractionated cells, whereas no response of the B cells could be observed to these mitogens providing that no contaminating T cells were present. Addition of T lymphocytes to these unresponsive B cells allowed them to respond to phytomitogens, but not to ALS. X-irradiated T cells could, to some extent, replace the diving T lymphocytes; no T-replacing factor could be found in cell-free supernatants from T cells, whether or not they had been activated by mitrogens. This model of B-T cooperation appears useful for studying the differentiation and maturation of human B lymphocytes.
Early detection of disease program: Evaluation of the cellular immune response
NASA Technical Reports Server (NTRS)
Criswell, B. S.; Knight, V.; Martin, R. R.; Kasel, J. A.
1974-01-01
The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.
Gori, Antonella; Ferrini, Francesco; Marzano, Maria Cristina; Tattini, Massimiliano; Centritto, Mauro; Baratto, Maria Camilla; Pogni, Rebecca; Brunetti, Cecilia
2016-01-01
Cistus incanus (Cistaceae) is a Mediterranean evergreen shrub. Cistus incanus herbal teas have been used as a general remedy in traditional medicine since ancient times. Recent studies on the antioxidant properties of its aqueous extracts have indicated polyphenols to be the most active compounds. However, a whole chemical characterisation of polyphenolic compounds in leaves of Cistus incanus (C. incanus) is still lacking. Moreover, limited data is available on the contribution of different polyphenolic compounds towards the total antioxidant capacity of its extracts. The purpose of this study was to characterise the major polyphenolic compounds present in a crude ethanolic leaf extract (CEE) of C. incanus and develop a method for their fractionation. Superoxide anion, hydroxyl and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assays were also performed to evaluate the antioxidant properties of the obtained fractions. Three different polyphenolic enriched extracts, namely EAC (Ethyl Acetate Fraction), AF1 and AF2 (Aqueos Fractions), were obtained from CEE. Our results indicated that the EAC, enriched in flavonols, exhibited a higher antiradical activity compared to the tannin enriched fractions (AF1 and AF2). These findings provide new perspectives for the use of the EAC as a source of antioxidant compounds with potential uses in pharmaceutical preparations. PMID:27548139
Tan, Wenbing; Xi, Beidou; Wang, Guoan; Jiang, Jie; He, Xiaosong; Mao, Xuhui; Gao, Rutai; Huang, Caihong; Zhang, Hui; Li, Dan; Jia, Yufu; Yuan, Ying; Zhao, Xinyu
2017-03-21
The electron transfer capacities (ETCs) of soil humic substances (HSs) are linked to the type and abundance of redox-active functional moieties in their structure. Natural temperature can affect the chemical structure of natural organic matter by regulating their oxidative transformation and degradation in soil. However, it is unclear if there is a direct correlation between ETC of soil HS and mean annual temperature. In this study, we assess the response of the electron-accepting and -donating capacities (EAC and EDC) of soil HSs to temperature by analyzing HSs extracted from soil set along glacial-interglacial cycles through loess-palaeosol sequences and along natural temperature gradients through latitude and altitude transects. We show that the EAC and EDC of soil HSs increase and decrease, respectively, with increasing temperature. Increased temperature facilitates the prevalence of oxidative degradation and transformation of HS in soils, thus potentially promoting the preferentially oxidative degradation of phenol moieties of HS or the oxidative transformation of electron-donating phenol moieties to electron-accepting quinone moieties in the HS structure. Consequently, the EAC and EDC of HSs in soil increase and decrease, respectively. The results of this study could help to understand biogeochemical processes, wherein the redox functionality of soil organic matter is involved in the context of increasing temperature.
Gaye, M. M.; Valentine, S. J.; Hu, Y.; Mirjankar, N.; Hammoud, Z. T.; Mechref, Y.; Lavine, B. K.; Clemmer, D. E.
2012-01-01
Three disease phenotypes, Barrett’s esophagus (BE), high-grade dysplasia (HGD), esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples are examined using a combination of ion mobility spectrometry (IMS), mass spectrometry (MS) and principal component analysis (PCA) techniques. Samples from a total of 136 individuals were examined, including: 7 characterized as BE, 12 as HGD, 56 as EAC and 61 as NC. In typical datasets it was possible to assign ~20 to 30 glycan ions based on MS measurements. Ion mobility distributions for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+ and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility features to low-mobility features vary significantly for different groups. The degree to which such variations in mobility profiles can be used to distinguish phenotypes is evaluated for eleven N-linked glycan ions. An outlier analysis on each sample class followed by an unsupervised PCA using a genetic algorithm for pattern recognition reveals that EAC samples are separated from NC samples based on 46 features originating from the 11-glycan composite IMS distribution. PMID:23126309
DOE Office of Scientific and Technical Information (OSTI.GOV)
Plessis, F.C.P. du; Willemse, C.A.
In this paper the radiological properties of a compensator material consisting of wax and gypsum is presented. Effective attenuation coefficients (EACs) have been determined from transmission measurements with an ion chamber in a Perspex phantom. Measurements were made at 80 and 100 cm source-to-skin distance (SSD) for beam energies of 6, 8, and 15 MV, for field sizes ranging from narrow beam geometries up to 40x40 cm{sup 2}, and at measurement depths of maximum dose build-up, 5 and 10 cm. A parametrization equation could be constructed to predict the EAC values within 4% uncertainty as a function of field sizemore » and depth of measurement. The EAC dependence on off-axis position was also quantified at each beam energy and SSD. It was found that the compensator material reduced the required thickness for compensation by 26% at 8 MV when compared to pure paraffin wax for a 10x10 cm{sup 2} field. Relative surface ionization (RSI) measurements have been made to quantify the effect of scattered electrons from the wax-gypsum compensator. Results indicated that for 80 cm SSD the RSI would exceed 50% for fields larger than 15x15 cm{sup 2}. At 100 cm SSD the RSI values were below 50% for all field sizes used.« less
Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium
Lawrenson, Kate; Pakzamir, Elham; Liu, Biao; Lee, Janet M.; Delgado, Melissa K.; Duncan, Kara; Gayther, Simon A.; Liu, Song; Roman, Lynda; Mhawech-Fauceglia, Paulette
2015-01-01
Background The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses. Methodology/Principal Findings We studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035). Conclusion Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future. PMID:26132201
Levi, Zohar; Kark, Jeremy D; Shamiss, Ari; Derazne, Estela; Tzur, Dorit; Keinan-Boker, Lital; Liphshitz, Irena; Niv, Yaron; Furman, Moshe; Afek, Arnon
2013-12-01
To the authors' knowledge, little work has been done concerning adolescent precursors for gastroesophageal cancer. In the current study, the association of adolescent overweight as well as socioeconomic status (SES) with the incidence of esophageal adenocarcinoma (EAC), gastroesophageal junction adenocarcinoma (GEJAC), and noncardia gastric cancer (NCGC) was evaluated. Body mass index (BMI) was measured in 1 million Israeli adolescent males who underwent a general health examination at a mean age of 17.3 ± 0.5 years from 1967 to 2005. Overweight was defined as a BMI ≥ 85th percentile of the standard US distribution in adolescence. Incident cancer was identified by linkage with the Israeli National Cancer Registry. A total of 182 incident cancer cases were documented (52 combined EAC and GEJAC cases and 130 NCGC cases). Adolescent overweight at baseline (BMI ≥ 85th percentile) was associated with an increased risk in the combined group of cases of EAC and GEJAC (multivariable hazards ratio [HR], 2.1; 95% confidence interval [95% CI], 1.1-4.3 [P = .032]). Low SES (the lowest category vs the highest) as well as low number of years of education (≤ 9 years) were associated with an increased risk of intestinal-type NCGC (multivariable HR, 2.2; 95% CI, 1.0-4.8 [P = .041] and multivariable HR, 1.9; 95% CI, 1.1-3.19 [P = .020], respectively). The adjusted risk of NCGC was higher in immigrants born in Asian countries and the former Soviet Union. Overweight during adolescence was found to be substantially associated with the subsequent development of EAC and GEJAC. In addition, although potential confounding by Helicobacter pylori infection status or lifestyle factors was not fully accounted for in the analyses, lower SES as well as immigration from higher-risk countries are important determinants of NCGC. © 2013 American Cancer Society.
Ryom, L; Boesecke, C; Bracchi, M; Ambrosioni, J; Pozniak, A; Arribas, J; Behrens, G; Mallon, Pgm; Puoti, M; Rauch, A; Miro, J M; Kirk, O; Marzolini, C; Lundgren, J D; Battegay, M
2018-05-01
The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non-alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug-drug interaction tables have been updated and new tables are included. Treatment options for direct-acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three-drug combination may be as effective as a five-drug regimen, and may reduce treatment duration from 18-24 to 6-10 months. Version 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages. © 2018 The Authors. HIV Medicine Published by John Wiley & Sons Ltd on behalf of British HIV Association.
Effect of aggregate graining compositions on skid resistance of Exposed Aggregate Concrete pavement
NASA Astrophysics Data System (ADS)
Wasilewska, Marta; Gardziejczyk, Wladysław; Gierasimiuk, Pawel
2018-05-01
The paper presents the evaluation of skid resistance of EAC (Exposed Aggregate Concrete) pavements which differ in aggregate graining compositions. The tests were carried out on concrete mixes with a maximum aggregate size of 8 mm. Three types of coarse aggregates were selected depending on their resistance to polishing which was determined on the basis of the PSV (Polished Stone Value). Basalt (PSV 48), gabbro (PSV 50) and trachybasalt (PSV 52) aggregates were chosen. For each type of aggregate three graining compositions were designed, which differed in the content of coarse aggregate > 4mm. Their content for each series was as follows: A - 38%, B - 50% and C - 68%. Evaluation of the skid resistance has been performed using the FAP (Friction After Polishing) test equipment also known as the Wehner/Schulze machine. Laboratory method enables to compare the skid resistance of different types of wearing course under specified conditions simulating polishing processes. In addition, macrotexture measurements were made on the surface of each specimen using the Elatexure laser profile. Analysis of variance showed that at significance level α = 0.05, aggregate graining compositions as well as the PSV have a significant influence on the obtained values of the friction coefficient μm of the tested EAC pavements. The highest values of the μm have been obtained for EAC with the lowest amount of coarse aggregates (compositions A). In these cases the resistance to polishing of the aggregate does not significantly affect the friction coefficients. This is related to the large areas of cement mortar between the exposed coarse grains. Based on the analysis of microscope images, it was observed that the coarse aggregates were not sufficiently exposed. It has been proved that PSV significantly affected the coefficient of friction in the case of compositions B and C. This is caused by large areas of exposed coarse aggregate. The best parameters were achieved for the EAC pavements with graining composition B and C and trachybasalt aggregate.
Meads, Catherine; Glover, Matthew; Dimmock, Paul; Pokhrel, Subhash
2016-12-01
As part of the development of the National Institute for Health and Care Excellence (NICE) Medical Technologies Guidance on Parafricta Bootees and Undergarments to reduce skin breakdown in people with, or at risk of, pressure ulcers, the manufacturer (APA Parafricta Ltd) submitted clinical and economic evidence, which was critically appraised by an External Assessment Centre (EAC) and subsequently used by the Medical Technologies Advisory Committee (MTAC) to develop recommendations for further research. The University of Birmingham and Brunel University, acting as a consortium, were commissioned to act as the EAC, independently appraising the submission. This article is an overview of the original evidence submitted, the EAC's findings and the final NICE guidance. Very little comparative evidence was submitted to demonstrate the effectiveness of Parafricta Bootees or Undergarments. The sponsor submitted a simple cost analysis to estimate the costs of using Parafricta in addition to current practice-in comparison with current practice alone-in hospital and community settings separately. The analysis took a National Health Service (NHS) perspective. The basis of the analysis was a previously published comparative study, which showed no statistical difference in average lengths of stay between patients who wore Parafricta Undergarments and Bootees, and those who did not. The economic model incorporated the costs of Parafricta but assumed shorter lengths of stay with Parafricta. The sponsor concluded that Parafricta was cost saving relative to the comparators. The EAC made amendments to the sponsor's analysis to correct for errors and to reflect alternative assumptions. Parafricta remained cost saving in most analyses, and the savings per prevalent case ranged from £757 in the hospital model to £3455 in the community model. All analyses were severely limited by the available data on effectiveness-in particular, a lack of good-quality comparative studies.
He, Huan; Huang, Bin; Fu, Gen; Xiong, Dan; Xu, Zhixiang; Wu, Xinhao; Pan, Xuejun
2018-06-15
The photochemical conversion and microbial transformation of pollutants mediated by dissolved organic matter (DOM), including 17α-ethinylestradiol (EE2), are often accompanied in natural water. However, there are few studies to explore the connection and mechanism between the two processes. This research aims to investigate the mechanism of DOM after electrochemically modification mediated EE2 combining photodegradation and biodegradation in the environment and it want to explain the natural phenomena of DOM after electrochemical advanced treatment entering the water environment mediated EE2 natural degradation. The results showed that combining photodegradation with biodegradation rates of EE2 mediated by DOM and electrochemically modified DOM (E-DOM) were promoted obviously. The efficiency of EE2 biodegradation was shown to be strongly correlated with electron accepting capacity (EAC) of DOM. Electrochemical modification can increase the EAC of DOM leading to EE2 biodegradation accelerated, and it also can form more triplet-state DOM moieties to promote the EE2 photodegradation in irradiation conditions, due to the increasing of quinone-type structures in DOM. Moreover, cell polymeric secretion (CPS) secreted from the microorganism could be stimulated to an excited state by irradiation, and that also accelerated EE2 degradation. Photolysis combined with biochemical degradation yielded less toxic degradation products. This study shows that the emission of DOM in wastewater after electrochemical treatment could accelerate estrogen degradation and play a positive role on the pollutant transformation in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.
8th Annual European Antibody Congress 2012
Beck, Alain; Carter, Paul J.; Gerber, Hans-Peter; Lugovskoy, Alexey A.; Wurch, Thierry; Junutula, Jagath R.; Kontermann, Roland E; Mabry, Robert
2013-01-01
The 8th European Antibody Congress (EAC), organized by Terrapin Ltd., was again held in Geneva, Switzerland, following on the tradition established with the 4th EAC. The new agenda format for 2012 included three parallel tracks on: (1) naked antibodies; (2) antibody drug conjugates (ADCs); and (3) bispecific antibodies and alternative scaffolds. The meeting started and closed with three plenary lectures to give common background and to share the final panel discussion and conclusions. The two day event included case studies and networking for nearly 250 delegates who learned of the latest advances and trends in the global development of antibody-based therapeutics. The monoclonal antibody track was focused on understanding the structure-function relationships, optimization of antibody design and developability, and processes that allow better therapeutic candidates to move through the clinic. Discussions on novel target identification and validation were also included. The ADC track was dedicated to evaluation of the ongoing success of the established ADC formats alongside the rise of the next generation drug-conjugates. The bispecific and alternative scaffold track was focused on taking stock of the multitude of bispecific formats being investigated and gaining insight into recent innovations and advancements. Mechanistic understanding, progression into the clinic and the exploration of multispecifics, redirected T cell killing and alternative scaffolds were extensively discussed. In total, nearly 50 speakers provided updates of programs related to antibody research and development on-going in the academic, government and commercial sectors. PMID:23493119
Assessing Anger Expression: Construct Validity of Three Emotion Expression-Related Measures
Jasinski, Matthew J.; Lumley, Mark A.; Latsch, Deborah V.; Schuster, Erik; Kinner, Ellen; Burns, John W.
2016-01-01
Self-report measures of emotional expression are common, but their validity to predict objective emotional expression, particularly of anger, is unclear. We tested the validity of the Anger Expression Inventory (AEI; Spielberger et al., 1985)), Emotional Approach Coping Scale (EAC; Stanton, Kirk, Cameron & Danoff-Burg, 2000), and Toronto Alexithymia Scale-20 (TAS-20; Bagby, Taylor, & Parker, 1994) to predict objective anger expression in 95 adults with chronic back pain. Participants attempted to solve a difficult computer maze by following the directions of a confederate who treated them rudely and unjustly. Participants then expressed their feelings for 4 minutes. Blinded raters coded the videos for anger expression, and a software program analyzed expression transcripts for anger-related words. Analyses related each questionnaire to anger expression. The AEI anger-out scale predicted greater anger expression, as expected, but AEI anger-in did not. The EAC emotional processing scale predicted less anger expression, but the EAC emotional expression scale was unrelated to anger expression. Finally, the TAS-20 predicted greater anger expression. Findings support the validity of the AEI anger-out scale but raise questions about the other measures. The assessment of emotional expression by self-report is complex and perhaps confounded by general emotional experience, the specificity or generality of the emotion(s) assessed, and self-awareness limitations. Performance-based or clinician-rated measures of emotion expression are needed. PMID:27248355
The European Astronaut Centre prepares for International Space Station operations.
Messerschmid, E; Haignere, J P; Damian, K; Damann, V
2004-04-01
The European Space Agency (ESA) contribution to the International Space Station (ISS) goes much beyond the delivery of hardware like the Columbus Laboratory, its payloads and the Automated Transfer Vehicles. ESA Astronauts will be members of the ISS crew. ESA, according to its commitments as ISS international partner, will be responsible to provide training on its elements and payloads to all ISS crewmembers and medical support for ESA astronauts. The European Astronaut Centre (EAC) in Cologne has developed over more than a decade into the centre of expertise for manned space activities within ESA by contributing to a number of important co-operative spaceflight missions. This role will be significantly extended for ISS manned operations. Apart from its support to ESA astronauts and their onboard operations, EAC will have a key role in training all ISS astronauts on ESA elements and payloads. The medical support of ISS crew, in particular of ESA astronauts has already started. This paper provides an overview on status and further plans in building up this homebase function for ESA astronauts and on the preparation towards Training Readiness for ISS crew training at EAC, Cologne. Copyright 2001 by the European Space Agency. Published by the American Institute of Aeronautics and Astronautics, Inc., with permission. Released to IAF/IAA/AIAA to publish in all forms. c2003 Elsevier Ltd. All rights reserved.
Jiang, Yang; Gong, Yuanzheng; Rubenstein, Joel H; Wang, Thomas D; Seibel, Eric J
2017-04-01
Multimodal endoscopy using fluorescence molecular probes is a promising method of surveying the entire esophagus to detect cancer progression. Using the fluorescence ratio of a target compared to a surrounding background, a quantitative value is diagnostic for progression from Barrett's esophagus to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). However, current quantification of fluorescent images is done only after the endoscopic procedure. We developed a Chan-Vese-based algorithm to segment fluorescence targets, and subsequent morphological operations to generate background, thus calculating target/background (T/B) ratios, potentially to provide real-time guidance for biopsy and endoscopic therapy. With an initial processing speed of 2 fps and by calculating the T/B ratio for each frame, our method provides quasireal-time quantification of the molecular probe labeling to the endoscopist. Furthermore, an automatic computer-aided diagnosis algorithm can be applied to the recorded endoscopic video, and the overall T/B ratio is calculated for each patient. The receiver operating characteristic curve was employed to determine the threshold for classification of HGD/EAC using leave-one-out cross-validation. With 92% sensitivity and 75% specificity to classify HGD/EAC, our automatic algorithm shows promising results for a surveillance procedure to help manage esophageal cancer and other cancers inspected by endoscopy.
Lee, V W Y; Chau, T S; Chan, A K W; Lee, K K C; Waye, M M Y; Ling, T K W; Chan, F K L
2010-06-01
Our study aimed to assess the effectiveness of esomeprazole or rabeprazole in combination with amoxicillin and clarithromycin for the eradication of Helicobacter pylori in Hong Kong non-ulcer dyspepsia (NUD) patients. A prospective clinical trial was conducted at the Alice Ho Miu ling Nethersole Hospital outpatient endoscopy center from June 2004 to December 2005. Participants received amoxicillin 1 g, clarithromycin 500 mg, and, esomeprazole 20 mg (EAC) or rabeprazole 20 mg (RAC), all given twice daily for 1 week. The H. pylori status was determined by the [13C] urea breath test at least 4 weeks after completion of the treatment. Mutation status of CYP2C19 in exon 4 and exon 5 associated with the poor metabolizer phenotype was determined. The intention-to-treat eradication rates in patients treated with RAC and EAC were 77% and 84.6% respectively, and per protocol-based eradication rates were 83.7% and 88.9% respectively. The eradication rates did not vary with CYP2C19 phenotype found. For clarithromycin-sensitive strains, the cure rates were statistically significant regardless of CYP2C19 polymorphism (P < 0.0001). Triple therapy with either EAC or RAC is effective for Hong Kong Chinese NUD patients with H. pylori infection. Success eradication was related to clarithromycin resistance and not CYP2C19 genotype.
Lelchuk, R; Cardoni, R L; Fuks, A S
1977-01-01
Peripheral leucocyte migration inhibition (LMI) with Trypanosoma cruzi-specific antigens, measured as a migration index (MI), was studied in chronic Chagas' disease patients. The MI of untreated patients with polymerized antigens from culture forms (epimastigotes) of T. cruzi was significantly lower than that of controls. In contrast, when chronic Chagas' patients were treated with nifurtimox, 10 mg/kg/day for 2 months, the MI was not different from control values. Treated and untreated patients had normal T- and B-lymphocyte markers, measured by the ability to form rosettes either with sheep erythrocytes (E-RFC) or with sheep erythrocytes--antibody--complement (EAC-RFC). In addition, the number of lymphocytes bearing surface membrane Ig (SMIg) was the same as that of controls. Non-specific functional assays, such as PHA-induced blastogenesis and antibody-dependent cell-mediated cytotoxicity (ADCC) to sensitized chicken erythrocytes were also normal, both in treated and untreated patients. Thus, nifurtimox produced a particularly effect on cell-mediated immunity, specially detectable using LMI. PMID:414867
Li, Jing; Chen, Xiaoxin; Shaker, Anisa; Oshima, Tadayuki; Shan, Jing; Miwa, Hiroto; Feng, Cheng; Zhang, Jun
2016-01-01
Gastroesophageal reflux disease (GERD) has become the most commonly seen gastrointestinal disorder in outpatient clinics. In the United States, around 20% of the general population experience heartburn on a weekly basis. Although clinical complaints can be mild or moderate, patients with GERD may develop further complications, such as peptic strictures, Barrett's esophagus (BE), and even esophageal adenocarcinoma (EAC). Pathologically, GERD is developed as a result of chronic and enhanced exposure of the esophageal epithelium to noxious gastric refluxate. In this review article, we provide an overview of GERD, and then focus on the roles of stromal cells, interleukin 4 (IL-4), and adiponectin in GERD and BE. The importance of inflammation and immunomodulators in GERD pathogenesis is highlighted. Targeting the immunomodulators or inflammation in general may improve the therapeutic outcome of GERD, in particular, in those refractory to proton pump inhibitors. PMID:27441783
Jain, Subheet K; Utreja, Puneet; Tiwary, Ashok K; Mahajan, Mohit; Kumar, Nikhil; Roy, Partha
2014-01-01
The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation. Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay (FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies. FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1% intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation (85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time (MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of paclitaxel.
Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex.
Biscaro, Fernanda; Parisotto, Eduardo Benedetti; Zanette, Vanilde Citadini; Günther, Tania Mara Fischer; Ferreira, Eduardo Antonio; Gris, Eliana Fortes; Correia, João Francisco Gomes; Pich, Claus Tröger; Mattivi, Fulvio; Filho, Danilo Wilhelm; Pedrosa, Rozangela Curi
2013-06-01
Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as "Sangue-de-Dragão". Its red latex is used traditionally for treating ulcers, diabetes and cancer. To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo. Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model. Phytochemical studies indicated a high phenol content of flavonols (45.67 ± 0.24 and 18.01 ± 0.23 mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 ± 1.84 and 1527.41 ± 16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC50 = 169.0 ± 1.8 and 187.0 ± 2.2 μg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced the body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%. These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.
Estimating the Velocity and Transport of the East Australian Current using Argo, XBT, and Altimetry
NASA Astrophysics Data System (ADS)
Zilberman, N. V.; Roemmich, D. H.; Gille, S. T.
2016-02-01
Western Boundary Currents (WBCs) are the strongest ocean currents in the subtropics, and constitute the main pathway through which warm water-masses transit from low to mid-latitudes in the subtropical gyres of the Atlantic, Pacific, and Indian Oceans. Heat advection by WBCs has a significant impact on heat storage in subtropical mode waters formation regions and at high latitudes. The possibility that the magnitude of WBCs might change under greenhouse gas forcing has raised significant concerns. Improving our knowledge of WBC circulation is essential to accurately monitor the oceanic heat budget. Because of the narrowness and strong mesoscale variability of WBCs, estimation of WBC velocity and transport places heavy demands on any potential sampling scheme. One strategy for studying WBCs is to combine complementary data sources. High-resolution bathythermograph (HRX) profiles to 800-m have been collected along transects crossing the East Australian Current (EAC) system at 3-month nominal sampling intervals since 1991. EAC transects, with spatial sampling as fine as 10-15 km, are obtained off Brisbane (27°S) and Sydney (34°S), and crossing the related East Auckland Current north of Auckland. Here, HRX profiles collected since 2004 off Brisbane are merged with Argo float profiles and 1000 m trajectory-based velocities to expand HRX shear estimates to 2000-m and to estimate absolute geostrophic velocity and transport. A method for combining altimetric data with HRX and Argo profiles to mitigate temporal aliasing by the HRX transects and to reduce sampling errors in the HRX/Argo datasets is described. The HRX/Argo/altimetry-based estimate of the time-mean poleward alongshore transport of the EAC off Brisbane is 18.3 Sv, with a width of about 180 km, and of which 3.7 Sv recirculates equatorward on a similar spatial scale farther offshore. Geostrophic transport anomalies in the EAC at 27°S show variability of ± 1.3 Sv at interannual time scale related to ENSO. The present calculation is a case study that will be extended to other subtropical WBCs.
Esophageal Helicobacter pylori colonization aggravates esophageal injury caused by reflux
Chu, Yun-Xiang; Wang, Wei-Hong; Dai, Yun; Teng, Gui-Gen; Wang, Shu-Jun
2014-01-01
AIM: To investigate esophageal Helicobacter pylori (H. pylori) colonization on esophageal injury caused by reflux and the related mechanisms. METHODS: An esophagitis model, with acid and bile reflux, was surgically produced in male rats. The rats were randomly divided into either: (1) an esophagogastroduodenal anastomosis (EGDA) group; (2) an EGDA with H. pylori infection group; (3) a pseudo-operation with H. pylori infection group; or (4) a pseudo-operation group. All rats were kept for 36 wk. Based on the location of H. pylori colonization, the EGDA rats with H. pylori infection were subdivided into those with concomitant esophageal H. pylori colonization or those with only gastric H. pylori colonization. The esophageal injuries were evaluated grossly and microscopically. The expressions of CDX2 and MUC2 were determined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Ki-67 antigen expression was determined by immunohistochemistry. The mRNA levels of cyclin D1, c-Myc, Bax and Bcl-2 were determined by RT-PCR. Cell apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method. RESULTS: Esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) developed in rats that underwent EGDA. When comparing rats with EGDA and concomitant esophageal H. pylori colonization to EGDA-only rats, the severity of injury (87.9 ± 5.2 vs 77.2 ± 8.6, macroscopically, 92.5 ± 8.0 vs 83.8 ± 5.5, microscopically, both P < 0.05) and the incidences of BE (80.0% vs 33.3%, P = 0.055) and EAC (60.0% vs 11.1%, P < 0.05) were increased. These increases were associated with upregulation of CDX2 and MUC2 mRNA (10.1 ± 5.4 vs 3.0 ± 2.9, 8.4 ± 4.6 vs 2.0 ± 3.2, respectively, Ps < 0.01) and protein (8.1 ± 2.3 vs 3.3 ± 3.1, 7.3 ± 4.0 vs 1.8 ± 2.7, respectively, all P < 0.05). The expression of Ki-67 (8.9 ± 0.7 vs 6.0 ± 1.7, P < 0.01) and the presence of apoptotic cells (8.3 ± 1.1 vs 5.3 ± 1.7, P < 0.01) were also increased significantly in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only. The mRNA levels of cyclin D1 (5.8 ± 1.9 vs 3.4 ± 1.3, P < 0.01), c-Myc (6.4 ± 1.7 vs 3.7 ± 1.2, P < 0.01), and Bax (8.6 ± 1.6 vs 5.1 ± 1.3, P < 0.01) were significantly increased, whereas the mRNA level of Bcl-2 (0.6 ± 0.3 vs 0.8 ± 0.3, P < 0.01) was significantly reduced in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only. CONCLUSION: Esophageal H. pylori colonization increases esophagitis severity, and facilitates the development of BE and EAC with the augmentation of cell proliferation and apoptosis in esophageal mucosa. PMID:25400455
Immunological responsiveness of frozen-thawed human lymphocytes.
Strong, D M; Woody, J N; Factor, M A; Ahmed, A; Sell, K W
1975-01-01
Mononuclear cells (10--20 X 10(6)) obtained from human peripheral blood by a standard Ficoll-Hypaque technique were suspended in RPMI 1640 media at 4 degrees C containing 10% foetal calf serum and 7-5% dimethyl sulphoxide (DMSO). Two-millilitre aliquots were cooled at -1 degree C/min in a Cryoson BV-4 programmed freezing system to -30 degrees C, then -5 degrees C/min to -80 degrees C and stored in liquid nitrogen vapor. On the day of testing, cell suspensions were thawed rapidly in a 37 degree C water bath. DMSO was diluted slowly out of the sample and cells resuspended in fresh RPMI 1640. It was found that frozen stored human lymphocytes (FSHL) demonstrated all the characteristics of fresh unfrozen cells. These included their ability to form spontaneous rosettes with sheep erythrocytes ('E' rosettes) and sheep erythrocyte--antibody--complement rosettes ('EAC' rosettes). The presence of surface immunoglobulins and Fc receptors were shown by membrane immunofluorescence to be comparable. In addition, the results show that FSHL respond to mitogens, specific antigens; act as both stimulators and responders in the mixed lymphocyte culture reaction; and exhibit cell-mediated lymphocytotoxicity following in vitro sensitization, or against antibody-coated target cells. PMID:128429
NASA Astrophysics Data System (ADS)
Aziz, Marwa A.; Serya, Rabah A. T.; Lasheen, Deena S.; Abdel-Aziz, Amal Kamal; Esmat, Ahmed; Mansour, Ahmed M.; Singab, Abdel Nasser B.; Abouzid, Khaled A. M.
2016-04-01
Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in cancer angiogenesis. In this study, a series of novel furo[2,3-d]pyrimidine and thieno[2,3-d]pyrimidine based-derivatives were designed and synthesized as VEGFR-2 inhibitors, in accordance to the structure activity relationship (SAR) studies of known type II VEGFR-2 inhibitors. The synthesized compounds were evaluated for their ability to in vitro inhibit VEGFR-2 kinase enzyme. Seven compounds (15b, 16c, 16e, 21a, 21b, 21c and 21e) demonstrated highly potent dose-related VEGFR-2 inhibition with IC50 values in nanomolar range, of which the thieno[2,3-d]pyrimidine based-derivatives (21b, 21c and 21e) exhibited IC50 values of 33.4, 47.0 and 21 nM respectively. Moreover, furo[2,3-d]pyrimidine-based derivative (15b) showed the strongest inhibition of human umbilical vein endothelial cells (HUVEC) proliferation with 99.5% inhibition at 10 μM concentration. Consistent with our in vitro findings, compounds (21b and 21e) orally administered at 5 and 10 mg/kg/day for 8 consecutive days demonstrated potent anticancer activity in Erhlich ascites carcinoma (EAC) solid tumor murine model. Such compounds blunted angiogenesis in EAC as evidenced by reduced percent microvessel via decreasing VEGFR-2 phosphorylation with subsequent induction of apoptotic machinery. Furthermore, Miles vascular permeability assay confirmed their antiangiogenic effects in vivo. Intriguingly, such compounds showed no obvious toxicity.
Natural History of the Post-ablation Esophagus.
Reed, Craig C; Shaheen, Nicholas J
2018-04-18
Endoscopic ablative therapy including radiofrequency ablation (RFA) represents the preferred management strategy for dysplastic Barrett's esophagus (BE) and appears to diminish the risk of developing esophageal adenocarcinoma (EAC). Limited data describe the natural history of the post-ablation esophagus. Recent findings demonstrate that recurrent intestinal metaplasia (IM) following RFA is relatively frequent. However, dysplastic BE and EAC subsequent to the complete eradication of intestinal metaplasia (CEIM) are uncommon. Moreover, data suggest that the risk of recurrent disease is probably highest in the first year following CEIM. Recurrent IM and dysplasia are usually successfully eradicated with repeat RFA. Future studies may refine surveillance intervals and inform the length of time surveillance should be conducted following RFA with CEIM. Further data will also be necessary to understand the utility of chemopreventive strategies, including NSAIDs, in reducing the risk of recurrent disease.
In situ Probe Microphone Measurement for Testing the Direct Acoustical Cochlear Stimulator.
Stieger, Christof; Alnufaily, Yasser H; Candreia, Claudia; Caversaccio, Marco D; Arnold, Andreas M
2017-01-01
Hypothesis: Acoustical measurements can be used for functional control of a direct acoustic cochlear stimulator (DACS). Background: The DACS is a recently released active hearing implant that works on the principle of a conventional piston prosthesis driven by the rod of an electromagnetic actuator. An inherent part of the DACS actuator is a thin titanium diaphragm that allows for movement of the stimulation rod while hermetically sealing the housing. In addition to mechanical stimulation, the actuator emits sound into the mastoid cavity because of the motion of the diaphragm. Methods: We investigated the use of the sound emission of a DACS for intra-operative testing. We measured sound emission in the external auditory canal (P EAC ) and velocity of the actuators stimulation rod (V act ) in five implanted ears of whole-head specimens. We tested the influence various positions of the loudspeaker and a probe microphone on P EAC and simulated implant malfunction in one example. Results: Sound emission of the DACS with a signal-to-noise ratio >10 dB was observed between 0.5 and 5 kHz. Simulated implant misplacement or malfunction could be detected by the absence or shift in the characteristic resonance frequency of the actuator. P EAC changed by <6 dB for variations of the microphone and loudspeaker position. Conclusion: Our data support the feasibility of acoustical measurements for in situ testing of the DACS implant in the mastoid cavity as well as for post-operative monitoring of actuator function.
The Footprint of Continental-Scale Ocean Currents on the Biogeography of Seaweeds
Wernberg, Thomas; Thomsen, Mads S.; Connell, Sean D.; Russell, Bayden D.; Waters, Jonathan M.; Zuccarello, Giuseppe C.; Kraft, Gerald T.; Sanderson, Craig; West, John A.; Gurgel, Carlos F. D.
2013-01-01
Explaining spatial patterns of biological organisation remains a central challenge for biogeographic studies. In marine systems, large-scale ocean currents can modify broad-scale biological patterns by simultaneously connecting environmental (e.g. temperature, salinity and nutrients) and biological (e.g. amounts and types of dispersed propagules) properties of adjacent and distant regions. For example, steep environmental gradients and highly variable, disrupted flow should lead to heterogeneity in regional communities and high species turnover. In this study, we investigated the possible imprint of the Leeuwin (LC) and East Australia (EAC) Currents on seaweed communities across ~7,000 km of coastline in temperate Australia. These currents flow poleward along the west and east coasts of Australia, respectively, but have markedly different characteristics. We tested the hypothesis that, regional seaweed communities show serial change in the direction of current flow and that, because the LC is characterised by a weaker temperature gradient and more un-interrupted along-shore flow compared to the EAC, then coasts influenced by the LC have less variable seaweed communities and lower species turnover across regions than the EAC. This hypothesis was supported. We suggest that this pattern is likely caused by a combination of seaweed temperature tolerances and current-driven dispersal. In conclusion, our findings support the idea that the characteristics of continental-scale currents can influence regional community organisation, and that the coupling of ocean currents and marine biological structure is a general feature that transcends taxa and spatial scales. PMID:24260352
Exposure to gastric juice may not cause adenocarcinogenesis of the esophagus
Cheng, Peng; Li, Jian-Sheng; Zhang, Lian-Feng; Chen, Yong-Zhong; Gong, Jun
2013-01-01
AIM: To determine the effects of gastric juice on the development of esophageal adenocarcinoma (EAC). METHODS: A animal model of duodenogastroesophageal reflux was established in Sprague-Dawley rats undergoing esophagoduodenostomy. The development of EAC and forestomach adenocarcinoma was investigated 40 wk after the treatment. Intraluminal pH and bile of the forestomach were measured. RESULTS: There were no significant differences in pH (t = 0.117, P = 0.925) or bile (χ2 = 0.036, P = 0.85) in the forestomach before and 40 wk after esophagoduodenostomy. There were also no significant differences between the model and controls during esophagoduodenostomy or 40 wk after esophagoduodenostomy. The incidence of intestinal metaplasia (88%) and intestinal metaplasia with dysplasia and adenocarcinoma (28%) in the esophagus in the model was higher than in the controls 40 wk after surgery (χ2 = 43.06, P < 0.001 and χ2 = 9.33, P = 0.002, respectively) and in the forestomach in the model (χ2 = 32.05, P < 0.001 and χ2 = 8.14, P = 0.004, respectively). The incidence rates of inflammation in the esophagus and forestomach were 100% and 96%, respectively (χ2 = 1.02, P = 0.31) in the model, which was higher than in the esophageal control (6.8%) (χ2 = 42.70, P < 0.001). CONCLUSION: Gastric juice exposure may not cause intestinal metaplasia with dysplasia or adenocarcinoma of the forestomach and may not be related to EAC. PMID:23613638
A western boundary current eddy characterisation study
NASA Astrophysics Data System (ADS)
Ribbe, Joachim; Brieva, Daniel
2016-12-01
The analysis of an eddy census for the East Australian Current (EAC) region yielded a total of 497 individual short-lived (7-28 days) cyclonic and anticyclonic eddies for the period 1993 to 2015. This was an average of about 23 eddies per year. 41% of the tracked individual cyclonic and anticyclonic eddies were detected off southeast Queensland between about 25 °S and 29 °S. This is the region where the flow of the EAC intensifies forming a swift western boundary current that impinges near Fraser Island on the continental shelf. This zone was also identified as having a maximum in detected short-lived cyclonic eddies. A total of 94 (43%) individual cyclonic eddies or about 4-5 per year were tracked in this region. The census found that these potentially displaced entrained water by about 115 km with an average displacement speed of about 4 km per day. Cyclonic eddies were likely to contribute to establishing an on-shelf longshore northerly flow forming the western branch of the Fraser Island Gyre and possibly presented an important cross-shelf transport process in the life cycle of temperate fish species of the EAC domain. In-situ observations near western boundary currents previously documented the entrainment, off-shelf transport and export of near shore water, nutrients, sediments, fish larvae and the renewal of inner shelf water due to short-lived eddies. This study found that these cyclonic eddies potentially play an important off-shelf transport process off the central east Australian coast.
Ten years of the European Astronaut Centre (EAC).
Messerschmid, E; Haignere, J P; Damian, K
2000-11-01
The European Astronaut Centre, the home base of ESA's Astronaut Corps, celebrated its 10th anniversary on 17 May 2000 with a media event highlighting the past, present and future of the Agency's manned space programme.
78 FR 28207 - Electricity Advisory Committee
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-14
... DEPARTMENT OF ENERGY Electricity Advisory Committee AGENCY: Office of Electricity Delivery and... a meeting of the Electricity Advisory Committee (EAC). The Federal Advisory Committee Act (Pub. L..., Arlington, Virginia 22203. FOR FURTHER INFORMATION CONTACT: Matthew Rosenbaum, Office of Electricity...
Spinning the Innovation and Entrepreneurship Mindset: A Modern Physics Approach
NASA Astrophysics Data System (ADS)
Roughani, Bahram
2010-04-01
Topics in Modern Physics course from relativity to quantum mechanics were examined in the context of innovation as part of the recent Kettering University program on ``Entrepreneurship Across Curriculum-EAC.'' The main goals were (a) to introduce innovation and entrepreneurship without eliminating any topics from this course, (b) to use EAC as a vehicle for intentional education that produces graduates with innovative mindsets, (c) to enrich the students learning experience aligned with the desired educational outcomes, and (d) to highlight the impact of scientific innovation in the society, while encouraging students to re-think how entrepreneurship mindset could maximize their impact in the society through innovation. Ideas such as principles behind innovation and innovative ideas, disciplines of innovations, formation of innovation teams, and effective methods for analyzing innovative value propositions were introduced in this course. Most of the implementation were achieved through out of class activities, and communicated through in class presentations, papers or weekly laboratory reports.
NASA Astrophysics Data System (ADS)
Rajak, D. K.; Deshpande, P. G.; Kumaraswamidhas, L. A.
2017-08-01
This Paper aimed at experimental investigation of compressive behaviour of square tube filled with pumice lightweight concrete (PLC). Square section of 20×20×30 mm is investigated, which is the backbone structure. The compression deformation result shows the better folding mechanism, displacement value, and energy absorption. PLC concrete filled with aluminium thin-wall tubes has been revealed superior energy absorption capacity (EAC) under low strain rate at room temperature. Superior EAC resulted as a result of mutual deformation benefit between aluminium section and PLC is also analysed. PLC was characterised by Fourier Transform Infrared (FTIR) and Field Emission Scanning Electron Microscopy (FESEM), and Energy Dispersive X-ray Spectrometry (EDX) analysis for better understanding of material behaviour. Individual and comparative load bearing graphs is logged for better prospective of analysing. Novel approach aimed at validation of porous lightweight concrete for better lightweight EA filler material.
Evaluation of Meteorological and Aerosol Sensing with small Unmanned Aerial Systems
NASA Astrophysics Data System (ADS)
Claussen, Johanna; Möhler, Ottmar; Leisner, Thomas; Brooks, Ian; Norris, Sarah; Brooks, Barbara; Hill, Martin; Haunold, Werner; Schrod, Jann; Danielczok, Anja
2013-04-01
Atmospheric aerosols have a large impact on the climate system due to their influence on the global radiation budget. Local aerosol sources such as vegetation, (bare) soil or industrial sites have to be quantified with high resolution data to validate aerosol transport models and improve the input for high resolution weather models. Our goal is to evaluate the use of Unmanned Aerial Systems (UAS) as a method for acquisition of high resolution meteorological and aerosol data. During the INUIT measurement campaign in August 2012 at mount Großer Feldberg near Frankfurt, Germany, several flights with different sensor packages were carried out. We measured basic meteorological parameters such as temperature, relative humidity and air pressure with miniaturized onboard sensors. In addition, the Compact Lightweight Aerosol Spectrometer Probe (CLASP) for aerosol size distribution measurement or the Electrostatic Aerosol Collector (EAC) for aerosol sample collection was installed on board. CLASP measures aerosol particles with diameters from 0.17 μm to 9.5 μm in up to 32 channels at a frequency of 10 Hz. The EAC collects air samples at 2 l/min onto a sample holder. After the flight the ice nuclei on the sample holder are activated and counted in the isothermal static diffusion chamber FRIDGE. The results from the INUIT campaign and additional calibration laboratory measurements show that UAS are a valuable platform for miniaturized sensors. The number of ice nuclei was determined with the EAC at 200m above ground level and compared to the reference measurement on the ground.
Neoadjuvant chemotherapy in technically unresectable carcinoma of external auditory canal
Joshi, Amit; Tandon, Nidhi; Noronha, Vanita; Dhumal, Sachin; Patil, Vijay; Arya, Supreeta; Juvekar, Shashikant; Agarwal, Jaiprakash; DCruz, Anil; Pai, Prathmesh; Prabhash, Kumar
2015-01-01
Background: Carcinoma of external auditory canal (EAC) is a very rare malignancy with surgical resection as the main modality of treatment. The outcomes with nonsurgical modalities are very dismal. We present a retrospective analysis of 4 patients evaluating the role of neoadjuvant chemotherapy in technically unresectable cancers. Materials and Methods: This is a retrospective analysis of 4 patients from our institute from 2010 to 2014 with carcinoma EAC who were deemed unfit for surgery due to extensive disease involving occipital bone with soft tissue infiltration (n = 2), temporal dura (n = 1), left temporal lobe, and extensive soft tissue involvement (n = 1). All these patients received neoadjuvant chemotherapy with docetaxel, cisplatin and 5 fluorouracil (n = 3) and paclitaxel and cisplatin (n = 1). Results: Response evaluation showed a partial response (PR) in 3 and stable disease (SD) in 1 patient by Response Evaluation Criteria in Solid Tumors criteria. All 3 patients who received 3 drug chemotherapy had PR while 1 patient who received 2 drug chemotherapy had SD. Two of these patients underwent surgery, and other 2 underwent definitive chemoradiation. One of 3 patients who achieved PR underwent surgical resection; the other 2 remained unresectable in view of the persistent intradural extension and infratemporal fossa involvement. One patient who had SD could undergo surgery in view of clearance of infraatemporal fossa. Recent follow-up shows that 3 out of these 4 patients are alive. Conclusion: This indicates that there may be a role of induction chemotherapy in converting potentially unresectable tumors to resectable disease that could produce better outcomes in carcinoma EAC. PMID:26855526
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, Tianyu NMI; Evans, Katherine J; Deng, Yi
In this study, an atmospheric river (AR) detection algorithm is developed to investigate the downstream modulation of the eastern North Pacific ARs by another weather extreme, known as the East Asian cold surge (EACS), in both reanalysis data and high-resolution global model simulations. It is shown that following the peak of an EACS, atmospheric disturbances of intermediate frequency (IF; 10 30 day period) are excited downstream. This leads to the formation of a persistent cyclonic circulation anomaly over the eastern North Pacific that dramatically enhances the AR occurrence probability and the surface precipitation over the western U.S. between 30 Nmore » and 50 N. A diagnosis of the local geopotential height tendency further confirms the essential role of IF disturbances in establishing the observed persistent anomaly. This downstream modulation effect is then examined in the two simulations of the National Center for Atmospheric Research Community Climate System Model version 4 with different horizontal resolutions (T85 and T341) for the same period (1979 2005). The connection between EACS and AR is much better captured by the T341 version of the model, mainly due to a better representation of the scale interaction and the characteristics of IF atmospheric disturbances in the higher-resolution model. The findings here suggest that faithful representations of scale interaction in a global model are critical for modeling and predicting the occurrences of hydrological extremes in the western U.S. and for understanding their potential future changes.« less
Self-worth and psychological adjustment of obese children: An analysis through the Draw-A-Person
Scimeca, Giuseppe; Alborghetti, Amelia; Bruno, Antonio; Troili, Giulia Maria; Pandolfo, Gianluca; Muscatello, Maria Rosaria Anna; Zoccali, Rocco Antonio
2016-01-01
AIM To investigate psychopathological correlates of child obesity via the Draw-A-Person test (DAP). METHODS The participants were 50 children with a mean age of 9.74 years. Body mass index (BMI) was used as a measure of body fat. Children were divided into normal (n = 17), overweight (n = 14) and obese (n = 19). Two qualitative methods of scoring the DAP based on an integrative approach were used to assess self-concept (ESW) and overall level of children’s adjustment (EAC). A procedure for judging interpretative skills of clinicians was implemented before they evaluated children’s drawings. RESULTS As predicted by our hypothesis, BMI was negatively correlated with ESW, r (50) = -0.29, P < 0.05, but not with EAC, r (50) = - 0.08, P = ns. To evaluate the effect of gender, Pearson correlations were re-computed regrouping the sample accordingly: BMI and EAC reached a significant negative correlation in female subjects, r (24) = -0.36, P < 0.05, and a positive correlation in male subjects, r (26) = 0.37, P = < 0.05; negative correlation between BMI and ESW became stronger in females, r (24) = -0.51, P < 0.01 but not in males, whose correlation disappeared resulting not-significant, r (26) = -0.06, P = ns. No effect of age was found. Results indicate that obesity has a negative correlation exclusively on overall adjustment and self-concept in female children. CONCLUSION It was concluded that there is a negative bias toward females that reveals how the stigma of obesity is widespread in Western society. PMID:27679772
Characterizing frontal eddies along the East Australian Current from HF radar observations
NASA Astrophysics Data System (ADS)
Schaeffer, Amandine; Gramoulle, A.; Roughan, M.; Mantovanelli, A.
2017-05-01
The East Australian Current (EAC) dominates the ocean circulation along south-eastern Australia, however, little is known about the submesoscale frontal instabilities associated with this western boundary current. One year of surface current measurements from HF radars, in conjunction with mooring and satellite observations, highlight the occurrence and propagation of meanders and frontal eddies along the inshore edge of the EAC. Eddies were systematically identified using the geometry of the high spatial resolution (˜1.5 km) surface currents, and tracked every hour. Cyclonic eddies were observed irregularly, on average every 7 days, with inshore radius ˜10 km. Among various forms of structures, frontal eddies associated with EAC meanders were characterized by poleward advection speeds of ˜0.3-0.4 m/s, migrating as far as 500 km south, based on satellite imagery. Flow field kinematics show that cyclonic eddies have high Rossby numbers (0.6-1.9) and enhance particle dispersion. Patches of intensified surface divergence at the leading edge of the structures are expected to generate vertical uplift. This is confirmed by subsurface measurements showing temperature uplift of up to 55 m over 24 h and rough estimates of vertical velocities of 10s of meters per day. While frontal eddies propagate through the radar domain independently of local wind stress, upfront wind can influence their stalling and growth, and can also generate large cold core eddies through intense shear. Such coherent structures are a major mechanism for the transport and entrainment of nutrient rich coastal or deep waters, influencing physical and biological dynamics, and connectivity over large distances.
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76 FR 59667 - Electricity Advisory Committee
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2011-09-27
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TECHNOLOGIES FOR RADON AND RADIONUCLIDE REMOVAL
This paper provides a summary of the technologies that are currently being used to remove radionuclides from drinking water. The radionuclides that are featured are the radionuclides currently regulated by EPA; radium, radon and uranium. Tehnologies effective for removal of eac...
The Physical Oceanography of Australia's Sunshine Coast
NASA Astrophysics Data System (ADS)
Ribbe, Joachim
2017-04-01
Australia's Sunshine coast is located to the south of the Great Barrier Reef and Fraser Island between about 25 oS to 28 oS. With a width of nearly 70-80 km, the eastern Australian continental shelf is at its widest here. The shelf region is referred to as the Southeast Queensland Marine Coastal Zone due to its unique physical oceanographic characteristics. The most prominent large-scale oceanic feature is the southward flowing East Australian Current (EAC). It forms to the north of Fraser Island from Coral Sea outflows, intensifies, and follows the continental shelf as a swift continental shelf hugging current but variable in strength; stronger in the southern hemisphere summer and weaker in winter. Little attention has been paid to the physical oceanography of this region, although important physical processes take place that drive regional marine environmental conditions, drive cross-shelf exchanges and interactions with the EAC, and that represent marine connectivity processes significant to the larger scale eastern Australian fisheries. This presentation reviews recent discoveries that include the Southeast Fraser Island Upwelling System, the Fraser Island Gyre, and document the role of cyclonic mesoscale eddies in driving cross-shelf exchanges and contribute to the formation of the Fraser Island Gyre. The Southeast Fraser Island Upwelling System appears to be predominately driven by the interaction of the EAC with the continental shelf leading to the establishment of one of eight important marine ecological hotspots along the east Australian coast. The Fraser Island Gyre is most prominent during the southern hemisphere autumn and winter months. It is characterised by on-shelf northerly flow, turning eastward south of Fraser Island before joining the EAC. It emerges that cyclonic eddy formation as well as the south-easterly trade winds drive the gyre's establishment and strength. A census of short-lived (7-28 days) cyclonic eddies, the first for any western boundary current region, found that the Southeast Queensland Marine Coastal Zone appears to be characterised by the highest number of eddies found along the east Australian Coast. About 43% of all eddies or about 4-5 per year were detected and tracked in this region. All these recent discoveries were made possible by analysing data provided via Australia's Integrated Marine Observing System (IMOS). A future effort is to be made to obtain additional in-situ data in order to support these new findings.
Murali, M; Mahendra, C; Hema, P; Rajashekar, N; Nataraju, A; Sudarshana, M S; Amruthesh, K N
2017-12-01
Sida acuta Burm.f. (Malvaceae) extracts are reported to have applications against malaria, diuretic, antipyretic, nervous and urinary diseases. No fungal endophytes of S. acuta are reported. Isolation, identification and evaluation of antibacterial, antioxidant, anticancer and haemolytic potential of fungal endophytes from the ethnomedcinal plant S. acuta. Sida acuta stem segments were placed on PDA medium to isolate endophytic fungi. The fungus was identified by genomic DNA analysis and phylogenetic tree was constructed using ITS sequences (GenBank) to confirm species. The antibacterial efficacy of Aspergillus sulphureus MME12 ethyl acetate extract was tested against Gram-positive and Gram-negative pathogenic bacteria. DPPH free radical scavenging activity, anticancer and DNA fragmentation against EAC cells, and direct haemolytic activity (100-500 μg/mL) using human erythrocytes were determined. The ethyl acetate extract of A. sulphureus (Fresen.) Wehmer (Trichocomaceae) demonstrated significant antibacterial potential against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella typhi compared to streptomycin. MIC against test pathogens was in the range of 15.6-62.5 μg/mL. The antioxidant results revealed significant RSA from 12.43% to 62.02% (IC 50 = 350.4 μg/mL, p ≤ 0.05). MME12 offered considerable inhibition of EAC proliferation (23% to 84%, IC 50 = 216.7 μg/mL, p ≤ 0.05) supported by DNA fragmentation studies. The extract also offered insignificant haemolysis (5.6%) compared to Triton X-100. A single endophytic fungus, A. sulphureus MME12 was isolated and identified using molecular profiling. The above-mentioned findings support the pharmacological application of A. sulphureus MME12 extract and demand for purification of the active principle(s).
Viruses, Other Pathogenic Microorganisms and Esophageal Cancer.
Xu, Wenji; Liu, Zhongshu; Bao, Quncha; Qian, Zhikan
2015-05-01
Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. Among the above-mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti-infection measures to prevent EC.
Intakes of citrus fruit and risk of esophageal cancer: A meta-analysis.
Zhao, Wenyue; Liu, Lu; Xu, Shun
2018-03-01
Esophageal cancer (EC) is the eighth most common cancer and the sixth most frequent cause of cancer death in the whole world. Many studies have investigated the association between citrus fruit intake and the risk of EC, but the results are inconsistent and not analyzed by category. We aimed to perform a meta-analysis of studies to evaluate the incidence between citrus fruit consumption and subtypes of esophageal cancer and derive a more precise estimation.Through searches of PubMed, OVID, and Web of Science we updated 1988 systematic review up to April 2016. Based on an inclusion and exclusion criteria, conventional meta-analysis according to DerSimonian and Laird method was used for the pooling of the results. Random-effect models were used to calculate subgroups.Twenty-five English articles (20 case-control studies and 5 cohort studies) comprising totally 5730 patients of esophageal cancer would be suitable for use in this study. The result indicated the inverse associations between intakes of citrus fruit and EC (relative risk [RR] = 0.65, 95% confidence interval [CI] 0.56-0.75, I = 51.1%, P = .001), Esophageal squamous cell carcinoma (ESCC) (RR = 0.59, 95% CI 0.47-0.76, I = 60.7%, P = .002), no significant relationship between citrus fruit and esophageal adenocarcinoma (EAC) (RR = 0.86, 95% CI 0.74-1.01, I = 0.0%, P = .598).This meta-analysis indicates that intakes of citrus fruit significantly reduce the risk of ESCC and is no obvious relationship with EAC. Further studies about constituents in citrus fruit and its mechanism are warranted.
Etiology and Prevention of Esophageal Cancer
Yang, Chung S.; Chen, Xiaoxin; Tu, Shuiping
2016-01-01
Background Esophageal cancer (EC) occurs commonly, especially in Asia, and is the sixth leading cause of cancer deaths worldwide. Recently, great progress has been made in research on the etiology and prevention of EC. Summary The major risk factors for esophageal squamous cell carcinoma (ESCC) are tobacco smoking and alcohol drinking, which act synergistically. Dietary parameters, including dietary carcinogens and insufficiency of micronutrients, could also be important risk factors in certain areas. A common etiological factor for both EC and some other cancers are low levels of intake of fruits and vegetables. With improvements in diet and drinking water in developing countries, the incidence of ESCC decreased. However, in economically well-developed countries, the incidence of esophageal adenocarcinoma (EAC) has markedly increased in the past 40 years. The major etiological factor for EAC is gastroesophageal reflux, which is also an etiological factor for gastric cardia adenocarcinoma (GCA). In certain areas of China, the occurrence of GCA is closely related to ESCC. Susceptibility genes for EC are starting to be discovered, and this may help to identify high-risk groups that have more need for preventive measures. Mitigation of the risk factors, early detection and treatment of precancerous lesions are effective approaches for prevention. Smoking cessation, avoidance of excessive alcohol, meat and caloric consumption, increasing physical activity and frequent consumption of vegetables and fruits are prudent lifestyle modifications for the prevention of EC as well as other diseases. Key Message The etiology of EC includes tobacco smoking, alcohol drinking, low levels of intake of fruits and vegetables as well as gastroesophageal reflux and susceptibility genes. Practical Implications A healthy lifestyle including smoking cessation, increasing physical activity, consumption of vegetables as well as reduction of alcohol intake and caloric consumption are major approaches to the prevention of EC. PMID:27722152
77 FR 10486 - Electricity Advisory Committee Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-22
... DEPARTMENT OF ENERGY Electricity Advisory Committee Meeting AGENCY: Office of Electricity Delivery... announces a meeting of the Electricity Advisory Committee (EAC). The Federal Advisory Committee Act (Pub. L... 20229. FOR FURTHER INFORMATION CONTACT: Matthew Rosenbaum, Office of Electricity Delivery and Energy...
76 FR 37103 - Electricity Advisory Committee
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2011-06-24
... DEPARTMENT OF ENERGY Electricity Advisory Committee AGENCY: Office of Electricity Delivery and... a meeting of the Electricity Advisory Committee (EAC). The Federal Advisory Committee Act (Pub. L...: David Meyer, Office of Electricity Delivery and Energy Reliability, U.S. Department of Energy, Forrestal...
75 FR 22577 - Proposed Privacy Policy Statement
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Screening Methods for Metal-Containing Nanoparticles in Water
Screening-level analysis of water for metal-containing nanoparticles is achieved with single particle-inductively coupled plasma mass spectrometry (SP-ICPMS). This method measures both the concentration of nanoparticles containing an analyte metal and the mass of the metal in eac...
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Tranzit XPress : hazardous material fleet management and monitoring system : evaluation report
DOT National Transportation Integrated Search
1997-07-01
In this report the evaluation performed on the first phase of the Tranzit XPress system is presented. The system comprises of a traffic/safety control center, motor vehicle instrumentation, and a variety of off vehicle tools that communicate with eac...
78 FR 55692 - Electricity Advisory Committee
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2013-09-11
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COMPUTATIONS ON THE PERFORMANCE OF PARTICLE FILTERS AND ELECTRONIC AIR CLEANERS
The paper discusses computations on the performance of particle filters and electronic air cleaners (EACs). The collection efficiency of particle filters and ACs is calculable if certain factors can be assumed or calibrated. For fibrous particulate filters, measurement of colle...
Kowalska, J D; Oprea, C; de Witt, S; Pozniak, A; Gökengin, D; Youle, M; Lundgren, J D; Horban, A
2017-05-01
The objective of this paper is to summarize the outcomes of the Euroguidelines in Central and Eastern Europe (ECEE) conference held in Warsaw in February 2016. The main aim of this conference was to facilitate a discussion on European AIDS Clinical Society (EACS) guidelines implementation across the region and neighbouring countries and to present the current obstacles in benchmarking HIV care in Europe. During a 2-day meeting, there were country-based presentations using a predefined template so as to make the data comparable and focus the discussion. Areas covered were country epidemiology, surveillance, national strategy for treatment and prevention, standards of care, access to care and treatment availability. Each participant filled in a questionnaire investigating HIV guidelines usage per country. In total, 16 Central and Eastern Europe (CEE) and neighbouring countries were represented at the conference: Albania, Armenia, Belarus, Croatia, Czech Republic, Estonia, Georgia, Hungary, Lithuania, Moldova, Poland, Romania, Russia, Serbia, Slovakia and Turkey. EACS guidelines version 7.1 were used in 14 (87%) countries. In 11 (69%) countries, national guidelines were available, of which eight had been recently updated. Half of the countries declared that they use World Health Organization (WHO) and Department of Health and Human Services (DHHS) guidelines, over one-third the European Centre for Disease Prevention and Control (ECDC) HIV testing guidelines and one in five the International Antiviral Society-USA (IAS-USA) Panel guidelines from 2012. Participants declared their will to promote the widespread use of EACS guidelines for HIV infection in the CEE region and neighbouring countries by signing the Warsaw Declaration. They also emphasized the need to increase publishing of data from national cohorts in that region. © 2016 British HIV Association.
Comparison of vonoprazan and proton pump inhibitors for eradication of Helicobacter pylori.
Shinozaki, Satoshi; Nomoto, Hiroaki; Kondo, Yoshie; Sakamoto, Hirotsugu; Hayashi, Yoshikazu; Yamamoto, Hironori; Lefor, Alan Kawarai; Osawa, Hiroyuki
2016-05-01
Alternative eradication therapies for Helicobacter pylori infection are needed because of an increasing failure rate over the past decade. The aim of this study was to determine if vonoprazan, a new potassium-competitive acid blocker, showed superiority to existing proton pump inhibitors for primary eradication of H. pylori in routine clinical practice. Data for 573 patients who underwent primary H. pylori eradication therapy were retrospectively reviewed. Regimens included clarithromycin 200 mg, amoxicillin 750 mg, and an acid-suppressing drug [lansoprazole 30 mg (LAC), rabeprazole 10 mg (RAC), esomeprazole 20 mg (EAC), or vonoprazan 20 mg (VAC)] twice daily for 1 week. Eradication was successful in 73% (419/573) of patients using intention-to-treat (ITT) analysis and 76% (419/549) of patients in per-protocol (PP) analysis. The VAC group had a significantly superior eradication rate compared with the LAC and RAC groups in ITT (VAC 83%, LAC 66% and RAC 67%, p < 0.01) and PP analysis (VAC 85%, LAC 69% and RAC 70%, p < 0.01), and had a similarly high eradication rate to the EAC group (83% in ITT and 87% in PP). Although the eradication rate in the VAC and EAC groups was not significantly higher than in the LAC and RAC groups in patients with mild gastric atrophy with both ITT and PP analyses, it was significantly higher in patients with severe gastric atrophy (p < 0.01). The VAC group had a significantly higher H. pylori eradication rate than the LAC and RAC groups, and a > 80% eradication rate regardless of the degree of atrophy. Copyright © 2016. Published by Elsevier Taiwan.
Klammer, Holger; Schlecht, Christiane; Wuttke, Wolfgang; Schmutzler, Cornelia; Gotthardt, Inka; Köhrle, Josef; Jarry, Hubertus
2007-09-05
Octyl-methoxycinnamate (OMC) is one of the most frequently used UV-filters in sunscreens to protect the skin against the noxious influence of UV radiation. Recently, OMC was suspected to act as an "endocrine active chemical" (EAC) with estrogenic actions. While EACs have been investigated thoroughly for interference with reproductive function in mammalians, surprisingly little efforts have been made to investigate an interference of EACs with the hypothalamo-pituitary-thyroid (HPT) axis despite the expression of estrogen receptors in all parts of this axis. Therefore, we conducted an in vivo study with ovariectomised rats treated for 5 days with different doses of OMC or 17beta-estradiol (E2) as a control. Determined parameters comprised serum levels of TSH, T4 and T3, hypothalamic TRH mRNA expression, protein-expression of the sodium-iodide-symporter (NIS) and the TSH receptor and the activities of thyroid peroxidase (TPO) in the thyroid and the T3-responsive hepatic type I 5'deiodinase (Dio1) in the liver. While E2 did not affect TSH-, T4- or T3-levels, OMC caused a dose-dependent decrease of serum concentrations of all of these hormones. TRH expression remained unaffected, while in the thyroid, expression of the TSH receptor but not of NIS was stimulated by OMC. TPO activity was unaltered but Dio1 activity was reduced by OMC. Thus, our results demonstrate a non-estrogenic interference of OMC within the rodent HPT axis with inadequate feedback response to impaired thyroid hormone status, indicated by decreased serum thyroid hormone and hepatic Dio1 levels.
Diet Composition affects surgery-associated weight loss in rats with a compromised alimentary tract
Aiyer, Harini S.; Li, Yan; Martin, Robert C.G.
2009-01-01
Background Esophageal adenocarcinoma (EAC) is the fastest growing cancer in terms of incidence and has a high mortality rate. The animal model to study EAC uses esophagoduodenal anastomosis (EDA) to induce mixed-reflux (bile/acid) causing esophagitis, barrett’s esophagus and EAC sequence within 6 months. However, the lack of fully functional stomach in these rats leads to the development of malnutrition. Methods We have assessed the ability of a chemically pure, purified ingredient diet (AIN-93M) to reduce surgery-associated malnutrition in rats that have undergone the EDA-surgery. Animals were either sham- (SH) or EDA-operated and fed either a grain-based rodent diet (RD) (SH-RD, n=3; EDA-RD, n=10) or a purified diet (PD) (SH-PD, n=4; EDA-PD, n=11). The animals were weighed periodically for assessment of weight gain and euthanized at the end of 24 weeks to measure esophageal tumor incidence. Results Animals that underwent sham surgery continued to gain weight throughout the study period and no tumors were detected. The EDA-operated animals had significantly lower weight gain compared with sham animals. There was no significant difference in weight gain among EDA animals fed 2 different types of diets until 9 weeks after the surgery. After 9 weeks, EDA–RD continued to lose weight significantly, whereas the weight loss leveled in EDA-PD (p<0.001). At termination, neither tissue histopathology nor tumor incidence was significantly different between the groups. Conclusion These results show that compared to a natural ingredient diet, a purified ingredient diet can reduce surgery-associated weight loss in rats with a compromised alimentary tract. This reduction in malnutrition has the potential to reduce the confounding effects of weight loss on future animal studies reported. PMID:19932903
Willits, Iain; Cole, Helen; Jones, Roseanne; Dimmock, Paul; Arber, Mick; Craig, Joyce; Sims, Andrew
2015-08-01
VibraTip™ was selected by the Medical Technologies Advisory Committee (MTAC) to undergo evaluation through the National Institute for Health and Care Excellence (NICE). VibraTip™ provides a vibratory stimulus for the purpose of detecting diabetic peripheral neuropathy (DPN) in patients with type 1 or 2 diabetes mellitus, and is intended to replace the current practice of using the 128 Hz tuning fork or 10 g monofilament (comparators). The sponsor (McCallan Medical) provided clinical and economic submissions which were evaluated by an External Assessment Centre (EAC). Of six diagnostic studies identified, the EAC considered that only one was directly relevant to the assessment. This study indicated VibraTip™ had a sensitivity of 0.79 (95 % CI 0.69-0.90) and specificity of 0.82 (95 % CI 0.74-0.90) for DPN using a neurothesiometer at 25 V as a reference standard. This was non-inferior to the comparators, but the sample size (n = 141) was too small to draw unequivocal conclusions and it is unclear how generalisable results were to clinical practice. The sponsor presented a de facto cost-minimisation model that in the base case showed minimal cost savings and, in sensitivity analysis which assumed diagnostic superiority of VibraTip™, showed large savings. The EAC appraised this model and concluded it was flawed as it was not evidence based and costs were likely to be unrealistic. The MTAC considered that the technology showed promise but decided the case for adoption was not proven, and therefore made a research recommendation as is reflected in NICE Medical Technology Guidance 22.
Sudo, Kazuki; Taketa, Takashi; Correa, Arlene M.; Campagna, Maria-Claudia; Wadhwa, Roopma; Blum, Mariela A.; Komaki, Ritsuko; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Skinner, Heath D.; Maru, Dipen M.; Rice, David C.; Swisher, Stephen G.; Hofstetter, Wayne L.; Ajani, Jaffer A.
2013-01-01
Purpose The primary purpose of surveillance of patients with esophageal adenocarcinoma (EAC) and/or esophagogastric junction adenocarcinoma after local therapy (eg, chemoradiotherapy followed by surgery or trimodality therapy [TMT]) is to implement a potentially beneficial salvage therapy to overcome possible morbidity/mortality caused by locoregional failure (LRF). However, the benefits of surveillance are not well understood. We report on LRFs and salvage strategies in a large cohort. Patients and Methods Between 2000 and 2010, 518 patients with EAC who completed TMT were analyzed for the frequency of LRF over time and salvage therapy outcomes. Standard statistical techniques were used. Results For 518 patients, the median follow-up time was 29.3 months (range, 1 to 149 months). Distant metastases (with or without LRF) occurred in 188 patients (36%), and LRF only occurred in 27 patients (5%). Eleven of 27 patients had lumen-only LRF. Most LRFs (89%) occurred within 36 months of surgery. Twelve patients had salvage chemoradiotherapy, but only five survived more than 2 years. Four patients needed salvage surgery, and three who survived more than 2 years developed distant metastases. The median overall survival of 27 patients with LRF was 17 months, and 10 patients (37%) survived more than 2 years. Thus, only 2% of all 518 patients benefited from surveillance/salvage strategies. Conclusion Our surveillance strategy, which is representative of many others currently being used, raises doubts about its effectiveness and benefits (along with concerns regarding types and times of studies and costs implications) to patients with EAC who have LRF only after TMT. Fortunately, LRFs are rare after TMT, but the salvage strategies are not highly beneficial. Our data can help develop an evidence-based surveillance strategy. PMID:24145339
Wastewater treatment plant (WWTP) effluents contain complex mixtures of chemicals, potentially including endocrine active chemicals (EACs), pharmaceuticals, and other contaminants of emerging concern (CECs). Due to the complex and variable nature of effluents, biological monitori...
77 FR 49441 - Electricity Advisory Committee
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-16
... recommendations to the Assistant Secretary for Electricity Delivery and Energy Reliability on programs to modernize the Nation's electric power system. Additionally, the renewal of the EAC has been determined to be... Energy Reliability, Department of Energy. ACTION: Notice of Renewal. SUMMARY: Pursuant to Section 14(a)(2...
USDA-ARS?s Scientific Manuscript database
Locoweeds are defined as Astragalus and Oxytropis species that cause intoxication from the alkaloid swainsonine. Swainsonine concentrations in Oxytropis sericea are influenced by location, plant part, and the developmental stage of the plant. Swainsonine concentrations follow similar trends at eac...
Waszak, Ilona; Dabrowska, Henryka; Komar-Szymczak, Katarzyna
2014-04-15
Groups of flounder (Platichthys flesus) females were collected in 2011 from the Vistula River and the Duoro River estuaries and corresponding reference sites in the southern Baltic Sea and Portuguese coast of the Atlantic Ocean to measure and compare the levels and profiles of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs). The estuaries' sediments were also investigated. Several differences were found in the POPs between the estuaries and between the two marine regions, which were highlighted by PCA. The Vistula River estuary POPs, significantly higher than in the Douro River estuary, were dominated by DDTs followed by PCBs. PBDEs levels, indifferent between the estuaries, were relatively low. The POP levels in flounder and sediment evaluated against environmental assessment criteria (EACs) indicated that none of the measured contaminants for which EAC had been established exceeded the criterion, except for CB-118 in flounder from the Vistula River estuary. Copyright © 2014 Elsevier Ltd. All rights reserved.
Giltrap, M; Ronan, J; Hardenberg, S; Parkes, G; McHugh, B; McGovern, E; Wilson, J G
2013-06-15
Candidate OSPAR/ICES recommended biomarkers at the level of the individual in Mytilus edulis for determination of good environmental status for MSFD were evaluated against contaminant levels at sites around Ireland. The sites chosen ranged from moderate to low pollution levels, but the actual ranking of the sites varied according to the contaminant levels present. At the most contaminated site, Cork, 4 out of 16 contaminants exceeded the EAC, while at Shannon, no EACs were exceeded. The SOS assay suggested that Cork was the healthiest site with a LT50 of 17.6 days, while SOS for Shannon was 15.6 days. Likewise, condition factors varied among sites and did not always correspond to contaminant-based status. There may be uncertainty in assigning status around the not good:good boundary. This raises potential difficulties not only in the biomarker/contaminant load relationship but also in the reliability of the biomarkers themselves and hence barriers meeting compliance levels. Copyright © 2013 Elsevier Ltd. All rights reserved.
Ueno, Nobuhiro; Shimizu, Akio; Kanai, Michiyuki; Iwaya, Yugo; Ueda, Shugo; Nakayama, Jun; Seo, Misuzu Kurokawa
2015-01-01
Deregulated expression of fibroblast growth factor receptors (FGFRs) and their ligands plays critical roles in tumorigenesis. The gene expression of an alternatively spliced isoforms of FGFR3, FGFR3IIIc, was analyzed by RT-PCR in samples from patients with esophageal carcinoma (EC), including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). The incidence of FGFR3IIIc was higher in EC [12/16 (75%); p=0.073] than in non-cancerous mucosa (NCM) [6/16 (38%)]. Indeed, an immunohistochemical analysis of early-stage ESCC showed that carcinoma cells expressing FGFR3IIIc stained positively with SCC-112, a tumor marker, and Ki67, a cell proliferation marker, suggesting that the expression of FGFR3IIIc promotes cell proliferation. We used EC-GI-10 cells endogenously expressing FGFR3IIIc as a model of ESCC to provide mechanistic insight into the role of FGFR3IIIc in ESCC. The knockdown of endogenous FGFR3 using siRNA treatment significantly abrogated cell proliferation and the overexpression of FGFR3IIIc in cells with enhanced cell proliferation. EC-GI-10 cells and ESCC from patients with EC showed endogenous expression of FGF2, a specific ligand for FGFR3IIIc, suggesting that the upregulated expression of FGFR3IIIc may create autocrine FGF signaling in ESCC. Taken together, FGFR3IIIc may have the potential to be an early-stage tumor marker and a molecular target for ESCC therapy. PMID:26487184
76 FR 32359 - Sunshine Act Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-06
... Sustainability. The Board will hear presentations by the National Institute of Standards and Technology (NIST... receive updates on EAC research and studies. The Board will hear a presentation on a Rutgers report on Voter Participation of People with Disabilities in 2010. The Board will hear other committee reports...
76 FR 29727 - Sunshine Act Notice
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-23
... Sustainability. The Board will hear presentations by the National Institute of Standards and Technology (NIST... receive updates on EAC research and studies. The Board will hear a presentation on a Rutgers report on Voter Participation of People with Disabilities in 2010. The Board will hear other committee reports...
Crystal growth furnace safety system validation
NASA Technical Reports Server (NTRS)
Mackowski, D. W.; Hartfield, R.; Bhavnani, S. H.; Belcher, V. M.
1994-01-01
The findings are reported regarding the safe operation of the NASA crystal growth furnace (CGF) and potential methods for detecting containment failures of the furnace. The main conclusions are summarized by ampoule leak detection, cartridge leak detection, and detection of hazardous species in the experiment apparatus container (EAC).
DOT National Transportation Integrated Search
2013-09-01
The interaction between the built environment, travel behavior and public health is now a major concern for both : researchers and urban planners. Currently, there is little empirical research that explores and examines the : relationship between eac...
The TURis System for Transurethral Resection of the Prostate: A NICE Medical Technology Guidance.
Cleves, Andrew; Dimmock, Paul; Hewitt, Neil; Carolan-Rees, Grace
2016-06-01
The transurethral resection in saline (TURis) system was notified by the company Olympus Medical to the National Institute of Health and Care Excellence's (NICE's) Medical Technologies Evaluation Programme. Following selection for medical technologies guidance, the company developed a submission of clinical and economic evidence for evaluation. TURis is a bipolar surgical system for treating men with lower urinary tract symptoms due to benign prostatic enlargement. The comparator is any monopolar transurethral resection of the prostate (mTURP) system. Cedar, a collaboration between Cardiff and Vale University Health Board, Cardiff University and Swansea University in the UK, acted as an External Assessment Centre (EAC) for NICE to independently critique the company's submission of evidence. Eight randomised trials provided evidence for TURis, demonstrating efficacy equivalent to that of mTURP for improvement of symptoms. The company presented meta-analyses of key outcome measures, and the EAC made methodological modifications in response to the heterogeneity of the trial data. The EAC analysis found that TURis substantially reduced the relative risks of transurethral resection syndrome (relative risk 0.18 [95 % confidence interval 0.05-0.62]) and blood transfusion (relative risk 0.35 [95 % confidence interval 0.19-0.65]). The company provided a de novo economic model comparing TURis with mTURP. The EAC critiqued the model methodology and made modifications. This found TURis to be cost saving at £70.55 per case for existing Olympus customers and cost incurring at £19.80 per case for non-Olympus customers. When an additional scenario based on the only available data on readmission (due to any cause) from a single trial was modelled, the estimated cost saving per case was £375.02 for existing users of Olympus electrosurgery equipment and £284.66 per case when new Olympus equipment would need to be purchased. Meta-analysis of eight randomised trials showed that TURis is associated with a statistically significantly reduced risk of transurethral resection syndrome and a reduced need for blood transfusion-two factors that may drive cost saving for the National Health Service. The clinical data are equivocal as to whether TURis shortens the hospital stay. Limited data from a single study suggest that TURis may reduce the rate of readmission after surgery. The NICE guidance supports adoption of the TURis technology for performing transurethral resection of the prostate in men with lower urinary tract symptoms due to benign prostatic enlargement.
The Fraser Gyre: A cyclonic eddy off the coast of eastern Australia
NASA Astrophysics Data System (ADS)
Azis Ismail, Mochamad Furqon; Ribbe, Joachim; Karstensen, Johannes; Lemckert, Charles; Lee, Serena; Gustafson, Johann
2017-06-01
This paper examines the on-shelf circulation of the eastern Australian continental shelf for a region off southeast Queensland. We identify a characteristic seasonally reoccurring wind-driven cyclonic flow. It influences the cross-shelf exchange with the East Australian Current (EAC), which is the western boundary current of the South Pacific Ocean. We refer to this cyclonic circulation as the Fraser Gyre. It is located south of Fraser Island between about 25 °S and 27 °S. The region is adjacent to the intensification zone of the EAC where the current accelerates and establishes a swift, albeit seasonally variable southward boundary flow. Through the analysis of several data sets including remotely sensed sea surface temperature and sea surface height anomaly, satellite tracked surface drifters, ocean and atmospheric reanalysis data as well as geostrophic currents from altimetry, we find that the on-shelf Fraser Gyre develops during the southern hemisphere autumn and winter months. The gyre is associated with a longshore near-coast northward flow. Maximum northward on-shelf depth averaged velocities are estimated with about 0.15-0.26 ms-1. The flow turns eastward just to the south of Fraser Island and joins the persistent southward EAC flow along the shelf break. The annual mean net cross-shelf outward and inward flow associated with the gyre is about -1.17 ± 0.23 Sv in the north and 0.23 ± 0.13 Sv (1 Sv = 106 m3s-1) in the south. Mean seasonal water renewal time scales of the continental shelf are longest during austral winter with an average of about 3.3 days due to the Fraser Gyre retaining water over the shelf, however, monthly estimates range from 2 to 8 days with the longer timescale during the austral autumn and winter. The southerly wind during austral autumn and winter is identified as controlling the on shelf circulation and is the principal driver of the seasonally appearing Fraser Gyre. The conceptual model of the Fraser Gyre is consistent with general physical principals of the coastal shelf circulation. A southerly wind is associated with surface layer flow toward the coast, a near coast positive SSHa with a current in the direction of the wind, down-welling and export of shelf water. The Fraser Gyre influenced cross-shelf exchanges are possibly facilitating the offshore transport of fish larvae, sediments, nutrients, river discharges, and other properties across the shelf break and into the southward flowing EAC during the austral autumn and winter.
Quantitative polymerase chain reaction (QPCR) can be used as a rapid method for detecting fecal indicator bacteria. Because false negative results can be caused by PCR inhibitors that co-extract with the DNA samples, an internal amplification control (IAC) should be run with eac...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-07-17
... Voting Survey; Comment Request AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY... Administration and Voting Survey) to the Director of the Office of Management and Budget for approval. The 2014 Election Administration and Voting Survey (Survey) asks election officials questions concerning voting and...
Federal Register 2010, 2011, 2012, 2013, 2014
2013-12-26
... Voting Survey; Comment Request AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY... Survey) to the Director of the Office of Management and Budget for approval. The 2014 Election Administration and Voting Survey (Survey) asks election officials questions concerning voting and election...
To assess the hazards and risks of possible endocrine active chemicals (EACs), there is a need for robust, validated test methods that detect perturbations of endocrine pathways and provide reliable information for evaluating potential adverse effects on apical endpoints. One iss...
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-12
... EAC (including your address and phone number) at U.S. Election Assistance Commission, 1225 New York... ELECTION ASSISTANCE COMMISSION Submission for OMB Review--2010 Election Administration and Voting... voters; (c) Number of new registrations in jurisdictions with Same Day Registration or Election Day...
ILEWG EuroMoonMars Research, Technology, and Field Simulation Campaigns
NASA Astrophysics Data System (ADS)
Foing, B. H.; Lillo, A.; Evellin, P.; Kołodziejczyk, A.; Heinicke, C.; Harasymczuk, M.; Authier, L.; Blanc, A.; Chahla, C.; Tomic, A.; Mirino, M.; Schlacht, I.; Hettrich, S.; Pacher, T.; Maller, L.; Decadi, A.; Villa-Massone, J.; Preusterink, J.; Neklesa, A.; Barzilay, A.; Volkova, T.
2017-10-01
ILEWG developed since 2008, "EuroMoonMars" pilot research with a Robotic Test Bench (ExoGeoLab) and a Mobile Laboratory Habitat (ExoHab) at ESTEC. Field campaigns were e.g. in ESTEC, EAC, at Utah MDRS, Eifel, and LunAres base at Pila Poland in 2017.
Feasibility of mercury removal from simulated flue gas by activated chars made from poultry manures
USDA-ARS?s Scientific Manuscript database
Increased emphasis on reduction of mercury emissions from coal fired electric power plants has resulted in environmental regulations that may in the future require application of activated carbons as mercury sorbents for mercury removal. At the same time, the quantity of poultry manure generated eac...
76 FR 13377 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-11
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, the U.S. Election...
75 FR 16764 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-02
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, the U.S. Election...
75 FR 6643 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-02-10
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, the U.S. Election...
75 FR 27743 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-18
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, the U.S. Election Assistance...
75 FR 39671 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-12
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, the U.S. Election...
75 FR 41454 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-16
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, the U.S. Election...
75 FR 75969 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-12-07
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, the U.S. Election...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-12
... countries. Relevant sectoral case studies (particularly for industries where EAC countries have significant... Commission, 500 E Street SW., Washington, DC 20436. The public record for this investigation may be viewed on... contact Margaret O'Laughlin, Office of External Relations (202-205-1819 or [email protected
75 FR 41691 - Nonprocurement Debarment and Suspension
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-19
..., whichever is lesser. EAC is also providing covered individuals a right to request a reconsideration of a... governments, in aggregate, or by the private sector of $100 million or more in any one year. [[Page 41692... procedures must I follow? Subpart A--General 5800.137 Who at the Commission may grant an exception to let an...
75 FR 4054 - Sunshine Act; Notice of Virtual Public Forum for EAC Board of Advisors
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-26
... Assessment. Phase II of the Election Operations Assessment contains threat trees for the seven types of voting types covered by the Election Operations Assessment. These threat trees are intended to capture risks to the various types of voting systems and the possible mitigations. These threat trees feed into...
Effect of lysozyme or antibiotics on fecal zoonotic pathogens in nursery pigs
USDA-ARS?s Scientific Manuscript database
Lysozyme is a 1,4-ß-N-acetylmuramidase that has antimicrobial properties. The objective of this study was to determine the effect of lysozyme and antibiotics on zoonotic pathogen shedding in feces in nursery pigs housed without and with an indirect disease challenge. Two replicates of 600 pigs eac...
To assess the hazards and risks of possible endocrine active chemicals (EACs) there is a need for robust, validated test methods that detect perturbation of endocrine pathways of concern and provide insights reliable information as to assess to potential adverse effects on apical...
Counseling Expectations among Mexican American College Students: The Role of Counselor Ethnicity.
ERIC Educational Resources Information Center
Abreu, Jose M.
2000-01-01
In this study, Mexican American undergraduates (N=65) completed a battery of tests about counseling services, including the Expectations About Counseling-Brief Form B (EAC-B) and the Marlowe-Crown Social Desirability Scale-From XX. Analysis determined that significant counselor ethnicity and participant gender main and interaction effects on the…
Using the methylome to identify aggressive Barrett’s esophagus — EDRN Public Portal
OVERALL STRATEGY: Our strategy will consist of using HumanMethylation450 arrays to identify methylation profiles and/or candidate methylated genes that distinguish BE from BE+LGD, BE+HGD and EAC (Aim 1). We will then assess whether these genes are predictive markers for aggressive BE (Aim 2)
45 CFR 90.34 - Agency reports.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 45 Public Welfare 1 2013-10-01 2013-10-01 false Agency reports. 90.34 Section 90.34 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE What are the Responsibilities of the Federal Agencies? § 90.34 Agency reports. Eac...
A fresh fruit and vegetable program improves high school students' consumption of fresh produce
USDA-ARS?s Scientific Manuscript database
Low fruit and vegetable intake may be associated with overweight. The United States Department of Agriculture implemented the Fresh Fruit and Vegetable Program in 2006-2007. One Houston-area high school was selected and received funding to provide baskets of fresh fruits and vegetables daily for eac...
Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma
Runge, Thomas M.; Abrams, Julian A.; Shaheen, Nicholas J.
2015-01-01
Barrett’s esophagus (BE) is a common condition, and is the precursor to esophageal adenocarcinoma, a disease with increasing burden in the western world, especially in Caucasian males. The incidence of BE increased dramatically during the late-20th century and incidence estimates continue to increase, with a prominent male:female ratio. The prevalence is between 0.5 – 2.0 percent. A number of anthropomorphic and behavioral risk factors exist for BE including obesity and tobacco smoking, but GERD is the strongest risk factor, and the risk is more pronounced with long-standing GERD. Esophageal adenocarcinoma (EAC) is the most common form of esophageal cancer in the U.S. Risk factors include GERD, tobacco smoking, and obesity, while NSAIDs and statins may be protective. A major factor predicting progression from non-dysplastic BE to EAC is the presence of dysplastic changes seen on esophageal histology, although a number of issues limit the utility of dysplasia as a marker for disease. Length of the involved BE segment is another risk for progression to high-grade dysplasia and cancer. Biomarkers have shown promise, but none are approved for clinical use. PMID:26021191
NASA Astrophysics Data System (ADS)
Pauline, Ong; Taib, Hariati; AzwirAzlan, Mohd; Fitriah Nasir, Nurul; Azham Azmi, Mohd; Salleh, Saliha Md; Zain, Badrul Aisham Md; Mahzan, Shahruddin; Hafeez Zainulabidin, Muhd; Ahmad, Sufizar; Rahman, Nasrull Abd; Ngali, Zamani; Rahman, Hamimah Abd
2017-01-01
Universiti Tun Hussein Onn Malaysia (UTHM) is the 15th of the 20 public universities established in Malaysia. UTHM consists of eight faculties. One of them is the Faculty of Mechanical and Manufacturing Engineering (FKMP). The programme offered - Bachelor of Mechanical Engineering with Honours (BDD), undergoes continuous auditing and accreditation by the Engineering Accreditation Council (EAC). To fulfill the requirement for accreditation, EAC requires the faculty to assess and evaluate the programme learning outcomes’ (PLOs) attainment of the graduates, such that all graduates are targeted to achieve the performance indicator (PI) upon graduation. This paper discusses the methods developed by the FKMP for PLOs’ measurement and evaluation. Two approaches are utilized in this regards, (i) the direct assessment based on students’ performance in courses, and (ii) the indirect assessment based the industrial and graduates’ perception. The PLOs’ attainment for graduates of cohort 2010-2012 are analysed in this study. Consolidation data shows that the PI for majority of the PLOs are achieved, indicating that the programme offered complies with the standard expected by different stakeholders.
Insights into the redox components of dissolved organic matters during stabilization process.
Yuan, Ying; Xi, Bei-Dou; He, Xiao-Song; Ma, Yan; Zhang, Hui; Li, Dan; Zhao, Xin-Yu
2018-05-01
The changes of dissolved organic matter (DOM) components during stabilization process play significant effects on its redox properties but are little reported. Composting is a stabilization process of DOM, during which both the components and electron transfer capacities (ETCs) of DOM change. The redox components within compost-derived DOM during the stabilization process are investigated in this study. The results show that compost-derived DOM contained protein-like, fulvic-like, and humic-like components. The protein-like component decreases during composting, whereas the fulvic- and humic-like components increase during the process. The electron-donating capacity (EDC), electron-accepting capacity (EAC), and ETC of compost-derived DOM all increase during composting but their correlations with the components presented significant difference. The humic-like components were the main functional component responsible for both EDC and ETC, whereas the protein- and fluvic-like components show negative effects with the EAC, EDC, and ETC, suggesting that the components within DOM have specific redox properties during the stabilization process. These findings are very meaningful for better understanding the geochemical behaviors of DOM in the environment.
Conjugated polymer energy level shifts in lithium-ion battery electrolytes.
Song, Charles Kiseok; Eckstein, Brian J; Tam, Teck Lip Dexter; Trahey, Lynn; Marks, Tobin J
2014-11-12
The ionization potentials (IPs) and electron affinities (EAs) of widely used conjugated polymers are evaluated by cyclic voltammetry (CV) in conventional electrochemical and lithium-ion battery media, and also by ultraviolet photoelectron spectroscopy (UPS) in vacuo. By comparing the data obtained in the different systems, it is found that the IPs of the conjugated polymer films determined by conventional CV (IPC) can be correlated with UPS-measured HOMO energy levels (EH,UPS) by the relationship EH,UPS = (1.14 ± 0.23) × qIPC + (4.62 ± 0.10) eV, where q is the electron charge. It is also found that the EAs of the conjugated polymer films measured via CV in conventional (EAC) and Li(+) battery (EAB) media can be linearly correlated by the relationship EAB = (1.07 ± 0.13) × EAC + (2.84 ± 0.22) V. The slopes and intercepts of these equations can be correlated with the dielectric constants of the polymer film environments and the redox potentials of the reference electrodes, as modified by the surrounding electrolyte, respectively.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lalonde, A; Bouchard, H
Purpose: To develop a general method for human tissue characterization with dual-and multi-energy CT and evaluate its performance in determining elemental compositions and the associated proton stopping power relative to water (SPR) and photon mass absorption coefficients (EAC). Methods: Principal component analysis is used to extract an optimal basis of virtual materials from a reference dataset of tissues. These principal components (PC) are used to perform two-material decomposition using simulated DECT data. The elemental mass fraction and the electron density in each tissue is retrieved by measuring the fraction of each PC. A stoichiometric calibration method is adapted to themore » technique to make it suitable for clinical use. The present approach is compared with two others: parametrization and three-material decomposition using the water-lipid-protein (WLP) triplet. Results: Monte Carlo simulations using TOPAS for four reference tissues shows that characterizing them with only two PC is enough to get a submillimetric precision on proton range prediction. Based on the simulated DECT data of 43 references tissues, the proposed method is in agreement with theoretical values of protons SPR and low-kV EAC with a RMS error of 0.11% and 0.35%, respectively. In comparison, parametrization and WLP respectively yield RMS errors of 0.13% and 0.29% on SPR, and 2.72% and 2.19% on EAC. Furthermore, the proposed approach shows potential applications for spectral CT. Using five PC and five energy bins reduces the SPR RMS error to 0.03%. Conclusion: The proposed method shows good performance in determining elemental compositions from DECT data and physical quantities relevant to radiotherapy dose calculation and generally shows better accuracy and unbiased results compared to reference methods. The proposed method is particularly suitable for Monte Carlo calculations and shows promise in using more than two energies to characterize human tissue with CT.« less
Gopalan, A; Paramanund, J; Shaw, P A; Patel, D; Friedman, J; Brophy, C; Buttenheim, A M; Troxel, A B; Asch, D A; Volpp, K G
2016-01-01
Objectives We compared the effectiveness of diabetes-focused messaging strategies at increasing enrolment in a healthy food programme among adults with diabetes. Methods Vitality is a multifaceted wellness benefit available to members of Discovery Health, a South Africa-based health insurer. One of the largest Vitality programmes is HealthyFood (HF), an incentive-based programme designed to encourage healthier diets by providing up to 25% cashback on healthy food purchases. We randomised adults with type 2 diabetes to 1 of 5 arms: (1) control, (2) a diabetes-specific message, (3) a message with a recommendation of HF written from the perspective of a HF member with diabetes, (4) a message containing a physician's recommendation of HF, or (5) the diabetes-specific message from arm 2 paired with an ‘enhanced active choice’(EAC). In an EAC, readers are asked to make an immediate choice (in this case, to enrol or not enrol); the pros and cons associated with the preferred and non-preferred options are highlighted. HF enrolment was assessed 1 month following the first emailed message. Results We randomised 3906 members. After excluding those who enrolled in HF or departed from the Vitality programme before the first intervention email, 3665 (94%) were included in a modified intent-to-treat analysis. All 4 experimental arms had significantly higher HF enrolment rates compared with control (p<0.0001 for all comparisons). When comparing experimental arms, the diabetes-specific message with the EAC had a significantly higher enrolment rate (12.6%) than the diabetes-specific message alone (7.6%, p=0.0016). Conclusions Messages focused on diabetes were effective at increasing enrolment in a healthy food programme. The addition of a framed active choice to a message significantly raised enrolment rates in this population. These findings suggest that simple, low-cost interventions can enhance enrolment in health promoting programmes and also be pragmatically tested within those programmes. Trial registration number NCT02462057. PMID:27903559
Tekes, Aylin; Ishman, Stacey L; Baugher, Katherine M; Brown, David J; Lin, Sandra Y; Tunkel, David E; Unalp-Arida, Aynur; Huisman, Thierry A G M
2013-07-01
This study aimed to determine the spectrum of temporal bone computed tomography (CT) abnormalities in children with conductive hearing loss (CHL) with and without microtia. From 1993 to 2008, a total of 3396 pediatric records including CHL were reviewed at our institution and revealed 180 cases of persistent CHL, 46 of whom had diagnostic temporal bone CT examinations. All of these examinations were systematically reviewed by two pediatric neuroradiologists, working in consensus, who had 5 and 18 years, respectively, of dedicated pediatric neuroradiology experience. Of the 46 children, 16 were boys and 30 were girls (age: 0.2-16 years; mean: 5 years). Also, 21 (46%) children had microtia and 25 (54%) children did not, as determined by clinical evaluation. External auditory canal atresia/stenosis (EAC-A/S) was the most common anomaly in both microtia and non-microtia groups. Two or more anomalies were observed in 18/21 children with microtia. The frequency of EAC-A/S was greater in children with microtia versus those without it (86% versus 32%, respectively; P = 0.0003). Syndromic diagnoses were also significantly more frequently made in children with microtia versus those without microtia (76% versus 20%, respectively; P = 0.0001). Temporal bone CT scans were normal in 10 children (22%) with persistent CHL. Microtia is an important finding in children with CHL. EAC and middle ear/ossicle anomalies were significantly more frequently seen in children with microtia, and multiple anomalies and bilateral microtia were more common in children with syndromic associations. These findings highlight the importance of understanding the embryological development of the temporal bone. The presence of one anomaly should raise suspicion of the possibility of other anomalies, especially in the setting of microtia. Bilateral microtia and multiple anomalies should also raise suspicion of genetic syndromes. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Effect of water content on stability of landslides triggered by earthquakes
NASA Astrophysics Data System (ADS)
Beyabanaki, S.; Bagtzoglou, A. C.; Anagnostou, E. N.
2013-12-01
Earthquake- triggered landslides are one of the most important natural hazards that often result in serious structural damage and loss of life. They are widely studied by several researchers. However, less attention has been focused on soil water content. Although the effect of water content has been widely studied for rainfall- triggered landslides [1], much less attention has been given to it for stability analysis of earthquake- triggered landslides. We developed a combined hydrology and stability model to investigate effect of soil water content on earthquake-triggered landslides. For this purpose, Bishop's method is used to do the slope stability analysis and Richard's equation is employed to model infiltration. Bishop's method is one the most widely methods used for analyzing stability of slopes [2]. Earthquake acceleration coefficient (EAC) is also considered in the model to analyze the effect of earthquake on slope stability. Also, this model is able to automatically determine geometry of the potential landslide. In this study, slopes with different initial water contents are simulated. First, the simulation is performed in the case of earthquake only with different EACs and water contents. As shown in Fig. 1, initial water content has a significant effect on factor of safety (FS). Greater initial water contents lead to less FS. This impact is more significant when EAC is small. Also, when initial water content is high, landslides can happen even with small earthquake accelerations. Moreover, in this study, effect of water content on geometry of landslides is investigated. For this purpose, different cases of landslides triggered by earthquakes only and both rainfall and earthquake for different initial water contents are simulated. The results show that water content has more significant effect on geometry of landslides triggered by rainfall than those triggered by an earthquake. Finally, effect of water content on landslides triggered by earthquakes during rainfall is investigated. In this study, after different durations of rainfall, an earthquake is applied to the model and the elapsed time in which the FS gets less than one obtains by trial and error. The results for different initial water contents and earthquake acceleration coefficients show that landslides can happen after shorter rainfall duration when water content is greater. If water content is high enough, the landslide occurs even without rainfall. References [1] Ray RL, Jacobs JM, de Alba P. Impact of unsaturated zone soil moisture and groundwater table on slope instability. J. Geotech. Geoenviron. Eng., 2010, 136(10):1448-1458. [2] Das B. Principles of Foundation Engineering. Stanford, Cengage Learning, 2011. Fig. 1. Effect of initial water content on FS for different EACs
EAC and the Development of National and European Gateways to Archives
ERIC Educational Resources Information Center
Ottosson, Per-Gunnar
2005-01-01
In the development of gateways to archives there are two different approaches, one focusing on the descriptions of the material and the other on the creators. Search and retrieval with precision and quality require controlled access points and name authority control. National registries of private archives have a long tradition in implementing the…
ERIC Educational Resources Information Center
American Association of Community Colleges, Washington, DC.
This program book contains progress reports for the colleges that participated in the American Association of Community Colleges' (AACC) Exploring America's Communities (EAC) project, which works to strengthen the teaching of American history, literature, and culture at the community college level. Parts 1, 2, and 3 describe the National…
75 FR 10228 - Publication of State Plan Pursuant to the Help America Vote Act; Correction
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-05
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act; Correction AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice; correction. SUMMARY: The U.S... caption to read: SUMMARY: Pursuant to sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA...
77 FR 23237 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-18
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, as amended by Section 622...
75 FR 51759 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-23
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Pub. L. 107-252, the U.S. Election Assistance...
77 FR 75425 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-20
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, as amended by Section 622...
ERIC Educational Resources Information Center
Tahir, Mohd Faizal Mat; Khamis, Nor Kamaliana; Wahid, Zaliha; Ihsan, Ahmad Kamal Ariffin Mohd; Ghani, Jaharah Ab; Sabri, Mohd Anas Mohd; Sajuri, Zainuddin; Abdullah, Shahrum; Sulong, Abu Bakar
2013-01-01
Universiti Kebangsaan Malaysia (UKM) is a research university that continuously undergoes an audit and accreditation process for the management of its courses. The Faculty of Engineering and the Built Environment (FKAB) is subjected to such processes, one of them is the auditing conducted by the Engineering Accreditation Council (EAC), which gives…
Federal Register 2010, 2011, 2012, 2013, 2014
2010-01-26
... Operations Assessment contains threat trees for the seven types of voting types covered by the Election Operations Assessment. These threat trees are intended to capture risks to the various types of voting systems and the possible mitigations. These threat trees feed into the Risk Assessment tool that will be...
Bone Conduction: Anatomy, Physiology, and Communication
2007-05-01
78 7.2 Human Localization Capabilities ..................................................................................84...main functions of the pinna are to direct incoming sound toward the EAC and to aid in sound localization . Some animals (e.g., dogs) can move their...pinnae to aid in sound localization , 9 but humans do not typically have this ability. People who may possess the ability to move their pinnae do
Curriculum Development Based on the Big Picture Assessment of the Mechanical Engineering Program
ERIC Educational Resources Information Center
Sabri, Mohd Anas Mohd; Khamis, Nor Kamaliana; Tahir, Mohd Faizal Mat; Wahid, Zaliha; Kamal, Ahmad; Ihsan, Ariffin Mohd; Sulong, Abu Bakar; Abdullah, Shahrum
2013-01-01
One of the major concerns of the Engineering Accreditation Council (EAC) is the need for an effective monitoring and evaluation of program outcome domains that can be associated with courses taught under the Mechanical Engineering program. However, an effective monitoring method that can determine the results of each program outcome using Bloom's…
In previous work we reported smallmouth bass populations in Northeastern Minnesota rivers and lakes with testicular oocyte (TOs) prevalence ranging from 7 to 59%, which is consistent with reports from other U.S. river systems. While it is often presumed that TOs are associated wi...
USDA-ARS?s Scientific Manuscript database
Our goal was to describe the effects of frying with various oils on the fatty acid content of rainbow trout. Four different oils were evaluated (peanut oil, high oleic sunflower oil, corn oil, and canola oil). Farmed rainbow trout (Oncorhynchus mykiss) fillets were sliced into three portions and eac...
USDA-ARS?s Scientific Manuscript database
The objective of this study was to compare prevalence of Campylobacter on the outside of broiler meat packages to the product inside the same packages. Chicken meat products were purchased at retail. Samples comprised whole carcasses and six different cut-up part products. Fifteen packages of eac...
78 FR 77110 - Publication of State Plan Pursuant to the Help America Vote Act
Federal Register 2010, 2011, 2012, 2013, 2014
2013-12-20
... ELECTION ASSISTANCE COMMISSION Publication of State Plan Pursuant to the Help America Vote Act AGENCY: U.S. Election Assistance Commission (EAC). ACTION: Notice. SUMMARY: Pursuant to Sections 254(a)(11)(A) and 255(b) of the Help America Vote Act (HAVA), Public Law 107-252, as amended by Section 622...
NASA Astrophysics Data System (ADS)
Hawkes, Adam; Leach, Matthew
The ability of combined heat and power (CHP) to meet residential heat and power demands efficiently offers potentially significant financial and environmental advantages over centralised power generation and heat-provision through natural-gas fired boilers. A solid oxide fuel cell (SOFC) can operate at high overall efficiencies (heat and power) of 80-90%, offering an improvement over centralised generation, which is often unable to utilise waste heat. This paper applies an equivalent annual cost (EAC) minimisation model to a residential solid oxide fuel cell CHP system to determine what the driving factors are behind investment in this technology. We explore the performance of a hypothetical SOFC system—representing expectations of near to medium term technology development—under present UK market conditions. We find that households with small to average energy demands do not benefit from installation of a SOFC micro-CHP system, but larger energy demands do benefit under these conditions. However, this result is sensitive to a number of factors including stack capital cost, energy import and export prices, and plant lifetime. The results for small and average dwellings are shown to reverse under an observed change in energy import prices, an increase in electricity export price, a decrease in stack capital costs, or an improvement in stack lifetime.
ERIC Educational Resources Information Center
Eisenberg, Diane U.; Labib, Nadya
This monograph documents the work of 41 participating community colleges in Exploring America's Communities (EAC): In Quest of Common Ground, a project stimulating a national conversation about American pluralism and identity, addressing such issues as what it means to be American, what brings us together and what divides us. Developed by the…
As part of a research effort examining system-wide responses of the hypothalamic-pituitary-gonadal (HPG) axis in fish to endocrine active chemicals (EACs) with different modes of action, we exposed zebrafish (Danio rerio) to 25 or 100 ìg/L of the aromatase inhibitor fadrozole for...
EAC training and medical support for International Space Station astronauts.
Messerschmid, E; Haignere, J P; Damian, K; Damann, V
2000-11-01
The operation of the International Space Station (ISS) will be a global multilateral endeavour. Each International Partner will be responsible for the operation of its elements and for providing a crew complement proportional to its share of the overall resources. The preparations of the European Astronaut Centre to furnish training and medical support for the ISS astronauts are described.
ERIC Educational Resources Information Center
Dollhausen, Karin; Lattke, Susanne; Scheliga, Felicia; Wolters, Andrä; Spexard, Anna; Geffers, Johannes; Banscherus, Ulf
2013-01-01
Widening adult participation in higher education as part of the development of lifelong learning strategies has been promoted by the European Union since the 1990s. Only recently, the 2011 Council resolution on a renewed European agenda for adult learning underlined the need to encourage higher education institutions to embrace adult learners. The…
Computationally Designed Oligomers for High Contrast Black Electrochromic Polymers
2017-05-05
SUBJECT TERMS electrochromics, DFf, TDDFT, organic electronics , oligomer, organic polymers 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF 18. NUMBER... electron -withdrawing behaviors. Another finding was that the same dication was produced regardless of the color or peak morphology of the neutral 5...radical cation states present in the chromophore upon oxidation. The two-ring electron rich dioxythiophene portions of the chromophore (EAc) and/or the
DCAA Contract Audit Manual. Volume 1, Chapters 1 - 11
1995-01-01
Office de Carvalho, Jenny Alexandria Branch Office Davids, Steve J. Melbourne Branch Office Dean, Clay Defense Contract Audit Institute Desert Valley...Justice DOL Department of Labor DOT Department of Transportation DPRO Defense Plant Representative Offices EAC Estimate At Completion (Cost) EDP...in the Department of De - vide accounting and financial advisory fense- services regarding contracts and subcon- tracts to all Department of Defense
Advanced Aircraft Electrical System (AAES). Definition and Prototype Design for F-14 Aircraft (GPMS)
1977-09-01
ften De . ate. _____________________ 1 UPRT DOCUMENTATION PAGE MAO ___________ NAA 4.TITLE (aWnd S.uCIoI) Aircraftn iiiuMiuz S. PERFORMING ORGANIZATION...STD 1553A Inter - faces ............ ............................ 4-1 APPENDIX Appendix Page A GPMS Signal List ....... ....................... .... A-I...Digital to analog DECM Defensive electronic countermeasures DEMUX (DMUX) Demultiplexer DES Designator D/L Data link DT Data terminal EAC Emergency ac
2013-03-01
killed just under 3,000 people and cost the U.S. economy somewhere between three and five trillion dollars. The Japanese attacked with a state... economy , and military readiness. The challenge is to design an Army Cyber force that can support the United States Cyber Command (USCYBERCOM) national...still keeps the intelligence and signal functions separate in most units today from battalion to echelon above Corps ( EAC ). There are many past reasons
Gopalan, A; Paramanund, J; Shaw, P A; Patel, D; Friedman, J; Brophy, C; Buttenheim, A M; Troxel, A B; Asch, D A; Volpp, K G
2016-11-30
We compared the effectiveness of diabetes-focused messaging strategies at increasing enrolment in a healthy food programme among adults with diabetes. Vitality is a multifaceted wellness benefit available to members of Discovery Health, a South Africa-based health insurer. One of the largest Vitality programmes is HealthyFood (HF), an incentive-based programme designed to encourage healthier diets by providing up to 25% cashback on healthy food purchases. We randomised adults with type 2 diabetes to 1 of 5 arms: (1) control, (2) a diabetes-specific message, (3) a message with a recommendation of HF written from the perspective of a HF member with diabetes, (4) a message containing a physician's recommendation of HF, or (5) the diabetes-specific message from arm 2 paired with an 'enhanced active choice'(EAC). In an EAC, readers are asked to make an immediate choice (in this case, to enrol or not enrol); the pros and cons associated with the preferred and non-preferred options are highlighted. HF enrolment was assessed 1 month following the first emailed message. We randomised 3906 members. After excluding those who enrolled in HF or departed from the Vitality programme before the first intervention email, 3665 (94%) were included in a modified intent-to-treat analysis. All 4 experimental arms had significantly higher HF enrolment rates compared with control (p<0.0001 for all comparisons). When comparing experimental arms, the diabetes-specific message with the EAC had a significantly higher enrolment rate (12.6%) than the diabetes-specific message alone (7.6%, p=0.0016). Messages focused on diabetes were effective at increasing enrolment in a healthy food programme. The addition of a framed active choice to a message significantly raised enrolment rates in this population. These findings suggest that simple, low-cost interventions can enhance enrolment in health promoting programmes and also be pragmatically tested within those programmes. NCT02462057. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
ESA Press Event: See Mars Express before its departure to the Red Planet
NASA Astrophysics Data System (ADS)
2002-08-01
There will be ten participants: four ESA astronauts (Pedro Duque, Leopold Eyharts, Paolo Nespoli and Thomas Reiter), four Japanese astronauts from NASDA (Takao Doi, Koichi Wakata, Satoshi Furukawa and Aikihido Hoshide) and two NASA astronauts (Nicole Passonno Stott and Stephanie D. Wilson). The main objective of this training session is to prepare the astronauts for the tasks they will have to perform when the Japanese experiment module (JEM) and ESA's Columbus laboratory are docked with the core of the International Space Station over the years ahead. After completing their training and certification, the astronauts will be assigned to long-duration missions to the ISS. The advanced training at the EAC will focus on the Columbus systems and the Automated Transfer Vehicle (ATV). It will consist of 24 classroom lectures on the Columbus and ATV systems and 4 on payloads, and 2 sessions in the Columbus Trainer. Instructors are being provided by Astrium for the Columbus systems and Alenia Spazio for the ATV, with ESA/EAC staff as mentors for the Columbus payloads. The astronauts are scheduled to visit Astrium in Bremen on 30 August to get acquainted with the flight unit of the Columbus laboratory module currently undergoing integration. This group of astronauts started their advanced training in April 2001 at NASA's Johnson Space Center (JSC), Houston, where they attended a first course on the US segment of the International Space Station. This was followed by training on the JEM system at NASDA's Tsukuba Space Center, Japan, in December 2001 - January 2002 and additional training at the JSC in May 2002. At the beginning of next year the group will be returning to Tsukuba for training on Japanese payloads. Hands-on sessions on Columbus Payload Training Models are scheduled for the second half of 2003, again at ESA's European Astronaut Centre. On Thursday 5 September, between 16:30 and 18:30 hrs, the astronauts and other ESA specialists will be available for interviews. Media representatives interested in meeting them are requested to complete the attached reply form and to fax it by Tuesday 3 September to Maren Stock at ESA/EAC.
Jin, Mingjie; Liu, Yanping; da Costa Sousa, Leonardo; Dale, Bruce E; Balan, Venkatesh
2017-08-01
High enzyme loading and low productivity are two major issues impeding low cost ethanol production from lignocellulosic biomass. This work applied rapid bioconversion with integrated recycle technology (RaBIT) and extractive ammonia (EA) pretreatment for conversion of corn stover (CS) to ethanol at high solids loading. Enzymes were recycled via recycling unhydrolyzed solids. Enzymatic hydrolysis with recycled enzymes and fermentation with recycled yeast cells were studied. Both enzymatic hydrolysis time and fermentation time were shortened to 24 h. Ethanol productivity was enhanced by two times and enzyme loading was reduced by 30%. Glucan and xylan conversions reached as high as 98% with an enzyme loading of as low as 8.4 mg protein per g glucan. The overall ethanol yield was 227 g ethanol/kg EA-CS (191 g ethanol/kg untreated CS). Biotechnol. Bioeng. 2017;114: 1713-1720. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Early Development of a Hazardous Chemical Protective Ensemble.
1986-10-01
Insuff. Cyanides ( Sodium , Potassium, Sol’n) -- 5 Butyl Cyanogen Bromide CBR 2 Insuff. Cyanogen Chloride CCL NR Insuff. Cyclohexane --- 6 Butyl...SPILLED SUBSTANCES ANNUAL RECOMMENDED ALTERNATE COMPOUND CHRIS CODE NO. OF SPILLS MATERIAL MATERIALS Dimethyl Sulfate DSL 4 Insuff. Ethyl Acrylate EAC 38...Tetrachloride STC 2 Insuff. Sodium Hydroxide (sol’n or dry) SHD 193 Butyl Sulfuric Acid SFA 426 CPE Tetrahydrofuran THF 13 None Titanium Tetrachloride TTT
Two groups of 15 male Sprague-Dawley rats weighing 225-250 g, were administered PB (1.3mg/kg/d, oral), DEET (40mg/kg/d, dermal), and permethrin (0.13mg/kg/d, dermal) for 28 days. Animals in one group were stressed by placing them in a Plexiglas restraint tube for 5 mins. eac...
Addressing the Challenges of Collective Security in West Africa: In View of Recent Conflicts
2017-06-09
Distribution is Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Understanding that achieving peace and security is a primary condition for an economic ...condition for an economic integration, ECOWAS has developped various approachs in resolving crises and overcoming threats within West Africa. Using...System CS Collective Security CSO Civil Society Organizations CSS Center for Security Studies EAC East Africa Community ECCAS Economic Community of
The Army Study Program Fiscal Year 1984 Report. Volume 2.
1984-01-01
TRADOC COMBINED ARMS I& A NUCLEAR ENVIRONMENT (CAKE) FDTE ATORT-D-001 TRADOC COMMAND CLIMATE ASSESSMENT DAPEH-E-042 DCSPER COMMUNICATIONS VISSION AREA ...ANALYSIS 2538 TRADOC COMMUNICATIONS MISSION AREA ANALYSIS. LEVEL II. ATZHC-E-002 TRADOC COMMUNICATIONS SUPPORT REQUIREMENTS ATZLC-E-002 TRADOC COMC...CORPS (EAC) AWCIS-D-002 SSI ECHELONS AFCVE CCRFS COMMUNICATIONS PISSION AREA ANALYSIS (EUROPE) CCOPS-D-002 USACC ECONOMIC IMPACT GENERATED AGAINST
Administration of Progress Payments at Defense Contract Management District-West
1993-08-05
the progress payment is calculated from the contractor’s incurred cost, the actual amount payable is always limited by the fair value of the...progress payments exceed the fair value of undelivered work. In addition to assessing the validity of the EAC relative to the progress payment request...were overpaid because Air Force Plant Representative Offices incorrectly calculated progress payment reductions for fair value of remaining work
NASA Astrophysics Data System (ADS)
Yamaguchi, Hiroki; Matsuda, Yu; Niimi, Tomohide
2017-07-01
Gas-surface interaction is studied by the molecular dynamics method to investigate qualitatively characteristics of accommodation coefficients. A large number of trajectories of gas molecules colliding to and scattering from a surface are statistically analyzed to calculate the energy (thermal) accommodation coefficient (EAC) and the tangential momentum accommodation coefficient (TMAC). Considering experimental measurements of the accommodation coefficients, the incident velocities are stochastically sampled to represent a bulk condition. The accommodation coefficients for noble gases show qualitative coincidence with experimental values. To investigate characteristics of these accommodation coefficients in detail, the gas-surface interaction is parametrically studied by varying the molecular mass of gas, the gas-surface interaction strength, and the molecular size of gas, one by one. EAC increases with increasing every parameter, while TMAC increases with increasing the interaction strength, but decreases with increasing the molecular mass and the molecular size. Thus, contradictory results in experimentally measured TMAC for noble gases could result from the difference between the surface conditions employed in the measurements in the balance among the effective parameters of molecular mass, interaction strength, and molecular size, due to surface roughness and/or adsorbed molecules. The accommodation coefficients for a thermo-fluid dynamics field with a temperature difference between gas and surface and a bulk flow at the same time are also investigated.
NASA Astrophysics Data System (ADS)
Kerry, Colette; Powell, Brian; Roughan, Moninya; Oke, Peter
2016-10-01
As with other Western Boundary Currents globally, the East Australian Current (EAC) is highly variable making it a challenge to model and predict. For the EAC region, we combine a high-resolution state-of-the-art numerical ocean model with a variety of traditional and newly available observations using an advanced variational data assimilation scheme. The numerical model is configured using the Regional Ocean Modelling System (ROMS 3.4) and takes boundary forcing from the BlueLink ReANalysis (BRAN3). For the data assimilation, we use an Incremental Strong-Constraint 4-Dimensional Variational (IS4D-Var) scheme, which uses the model dynamics to perturb the initial conditions, atmospheric forcing, and boundary conditions, such that the modelled ocean state better fits and is in balance with the observations. This paper describes the data assimilative model configuration that achieves a significant reduction of the difference between the modelled solution and the observations to give a dynamically consistent "best estimate" of the ocean state over a 2-year period. The reanalysis is shown to represent both assimilated and non-assimilated observations well. It achieves mean spatially averaged root mean squared (rms) residuals with the observations of 7.6 cm for sea surface height (SSH) and 0.4 °C for sea surface temperature (SST) over the assimilation period. The time-mean rms residual for subsurface temperature measured by Argo floats is a maximum of 0.9 °C between water depths of 100 and 300 m and smaller throughout the rest of the water column. Velocities at several offshore and continental shelf moorings are well represented in the reanalysis with complex correlations between 0.8 and 1 for all observations in the upper 500 m. Surface radial velocities from a high-frequency radar array are assimilated and the reanalysis provides surface velocity estimates with complex correlations with observed velocities of 0.8-1 across the radar footprint. A comparison with independent (non-assimilated) shipboard conductivity temperature depth (CTD) cast observations shows a marked improvement in the representation of the subsurface ocean in the reanalysis, with the rms residual in potential density reduced to about half of the residual with the free-running model in the upper eddy-influenced part of the water column. This shows that information is successfully propagated from observed variables to unobserved regions as the assimilation system uses the model dynamics to adjust the model state estimate. This is the first study to generate a reanalysis of the region at such a high resolution, making use of an unprecedented observational data set and using an assimilation method that uses the time-evolving model physics to adjust the model in a dynamically consistent way. As such, the reanalysis potentially represents a marked improvement in our ability to capture important circulation dynamics in the EAC. The reanalysis is being used to study EAC dynamics, observation impact in state-estimation, and as forcing for a variety of downscaling studies.
A Computer-Automated Temperature Control System for Semiconductor Measurements.
1979-11-01
Engineer: Jerry Silverman (RADC/ESE) temperature controller silicon devices data acquisition system mini-computer control application semiconductor dovice...characterization semiconductor materijals characterization silicon .’ AtlI EAC T 1 -fI I,,’-, *- s t ---v,.1.,,~ - d,f101h ir- IA i lr A computer...depends on the composition of the metals and the temperature of the junction. As the temperature of the junction increases so does the voltage at the
USDA-ARS?s Scientific Manuscript database
In order to provide an informational tool for assessing and prioritizing germplasm needs for ex situ conservation in the U.S. National Plant Germplasm System (NPGS), the USDA Agricultural Research Service in 2008 initiated a project to identify crop wild relatives (CWR) of major and minor crops. Eac...
Applying Financial Portfolio Analysis to Government Program Portfolios
2007-06-01
himself points out, “The Rational Man, like the unicorn , does not exist” (Markowitz, 1959). The various investor assumptions presented above break down...originally envisioned benefits quickly grow (Levine, 2005). As a recent Government Accountability Office report notes, the sheer size of IT spending in the...shows no change in EAC for the first three quarters and a decrease in the fourth quarter- although the SV and CV shrink and grow during the same period
2014-01-01
Background Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO consortium, new cell line cells, upper level alignment with the Cell Ontology (CL) and the Ontology for Biomedical Investigation, and logical extensions. Construction and content Collaboration among the CLO, CL, and OBI has established consensus definitions of cell line-specific terms such as ‘cell line’, ‘cell line cell’, ‘cell line culturing’, and ‘mortal’ vs. ‘immortal cell line cell’. A cell line is a genetically stable cultured cell population that contains individual cell line cells. The hierarchical structure of the CLO is built based on the hierarchy of the in vivo cell types defined in CL and tissue types (from which cell line cells are derived) defined in the UBERON cross-species anatomy ontology. The new hierarchical structure makes it easier to browse, query, and perform automated classification. We have recently added classes representing more than 2,000 cell line cells from the RIKEN BRC Cell Bank to CLO. Overall, the CLO now contains ~38,000 classes of specific cell line cells derived from over 200 in vivo cell types from various organisms. Utility and discussion The CLO has been applied to different biomedical research studies. Example case studies include annotation and analysis of EBI ArrayExpress data, bioassays, and host-vaccine/pathogen interaction. CLO’s utility goes beyond a catalogue of cell line types. The alignment of the CLO with related ontologies combined with the use of ontological reasoners will support sophisticated inferencing to advance translational informatics development. PMID:25852852
A web-based endpoint adjudication system for interim analyses in clinical trials.
Nolen, Tracy L; Dimmick, Bill F; Ostrosky-Zeichner, Luis; Kendrick, Amy S; Sable, Carole; Ngai, Angela; Wallace, Dennis
2009-02-01
A data monitoring committee (DMC) is often employed to assess trial progress and review safety data and efficacy endpoints throughout a trail. Interim analyses performed for the DMC should use data that are as complete and verified as possible. Such analyses are complicated when data verification involves subjective study endpoints or requires clinical expertise to determine each subject's status with respect to the study endpoint. Therefore, procedures are needed to obtain adjudicated data for interim analyses in an efficient manner. In the past, methods for handling such data included using locally reported results as surrogate endpoints, adjusting analysis methods for unadjudicated data, or simply performing the adjudication as rapidly as possible. These methods all have inadequacies that make their sole usage suboptimal. For a study of prophylaxis for invasive candidiasis, adjudication of both study eligibility criteria and clinical endpoints prior to two interim analyses was required. Because the study was expected to enroll at a moderate rate and the sponsor required adjudicated endpoints to be used for interim analyses, an efficient process for adjudication was required. We created a web-based endpoint adjudication system (WebEAS) that allows for expedited review by the endpoint adjudication committee (EAC). This system automatically identifies when a subject's data are complete, creates a subject profile from the study data, and assigns EAC reviewers. The reviewers use the WebEAS to review the subject profile and submit their completed review form. The WebEAS then compares the reviews, assigns an additional review as a tiebreaker if needed, and stores the adjudicated data. The study for which this system was originally built was administratively closed after 10 months with only 38 subjects enrolled. The adjudication process was finalized and the WebEAS system activated prior to study closure. Some website accessibility issues presented initially. However, once these issues were resolved, the reviewers found the system user-friendly and easy to navigate. Web-based data adjudication depends upon expeditious data collection and verification. Further, ability to use web-based technologies, in addition to clinical expertise, must be considered in selecting EAC members. The automated nature of this system makes it a practical mechanism for ensuring timely endpoint adjudication. The authors believe a similar approach could be useful for handling endpoint adjudication for future clinical trials.
Primary prevention with statins in cardiovascular diseases: A Saudi Arabian perspective.
Mahmood, D; Jahan, K; Habibullah, K
2015-07-01
Cardiovascular disease (CVD) constitutes one of the major causes of deaths and disabilities, globally claiming 17.3 million lives a year. Incidence of CVD is expected to rise to 25 million by 2030, and Saudi Arabia, already witnessing a rapid rise in CVDs, is no exception. Statins are the drugs of choice in established CVDs. In the recent past, evidence was increasingly suggesting benefits in primary prevention. But over the last decade Saudi Arabia has a witnessed significant rise in CVD-related deaths. Smoking, high-fat, low-fiber dietary intake, lack of exercise, sedentary life, high blood cholesterol and glucose levels were reported as frequent CVD-risk factors among Saudis, who may therefore be considered for primary prevention with statin. The prevalence of dyslipidemia, in particular, indicates that treatment should be directed at reducing the disorder with lipid-modifying agents and therapeutic lifestyle changes. The recent American College of Cardiology (ACC)/American Heart Association (AHA) guidelines has reported lowering the low-density lipoprotein cholesterol (LDL-C) target levels, prescribed by the 2011 European Society of Cardiology (ESC)/the European Atherosclerosis Society (EAS). The new ACC/AHA guidelines have overemphasized the use of statin while ignoring lipid targets, and have recommended primary prevention with moderate-intensity statin to individuals with diabetes aged 40-75 years and with LDL-C 70-189 mg/dL. Treatment with statin was based on estimated 10-year atherosclerotic-CVD (ASCVD) risk in individuals aged 40-75 years with LDL-C 70 to 189 mg/dL and without clinical ASCVD or diabetes. Adoption of the recent ACC/AHA guidelines will lead to inclusion of a large population for primary prevention with statins, and would cause over treatment to some who actually would not need statin therapy but instead should have been recommended lifestyle modifications. Furthermore, adoption of this guideline may potentially increase the incidences of statin intolerance and side-effects. On the other hand, the most widely used lipid management guideline, the 2011 ESC/EAC guidelines, targets lipid levels at different stages of disease activity before recommending statins. Hence, the 2011 ESC/EAC still offers a holistic and pragmatic approach to treating lipid abnormalities in CVD. Therefore, it is the 2011 ESC/EAC guidelines, and not the recent ACC/AHA guidelines, that should be adopted to draw guidance on primary prevention of CVD in Saudi Arabia.
Webster, L; Russell, M; Walsham, P; Phillips, L A; Packer, G; Hussy, I; Scurfield, J A; Dalgarno, E J; Moffat, C F
2009-06-01
Farmed, rope grown mussels (Loch Etive and Loch Ewe, both on the west coast of Scotland) and wild mussels (Straad on the west coast and Shell Bay and Aberdeen Breakwater, both on the east coast of Scotland) were collected on a monthly basis and analysed for persistent organic pollutants (POPs) with the aim of assessing the status of Scottish mussels, with respect to concentrations of POPs, and investigating site-specific and seasonal differences. Samples were analysed for polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs) and chlorobiphenyls (CBs). Total PAH (2- to 6-ring parent and alkylated) concentrations in mussels from three pristine sites (ref. 1: ICES Marine Chemistry Working Group Report 2008, http://www.ices.dk/reports/MHC/2007/MCWG07.pdf) (Loch Etive, Loch Ewe and Straad) were significantly lower than in mussels from sites with greater coastal influences (Aberdeen Breakwater and Shell Bay). Seasonal trends in the PAH concentrations were evident at the pristine sites, with concentrations being significantly higher for samples collected between November and March compared to those collected between April and October. The PAH data was assessed using a recently proposed traffic light system, based on the assessment criteria adopted by OSPAR for use in the 2008 Coordinated Environmental Monitoring Programme (CEMP) assessment. Concentrations were compared to Background Assessment Concentrations (BAC; blue/green transition) and Environmental Assessment Concentrations (EACs; green/red transition). All sites were classed as 'green' for the PAHs analysed, being below EACs, where available. The pristine sites were also below BACs for some PAHs and therefore would be classed as 'blue' for these PAHs. CBs and PBDEs were measured in mussels collected between 2006 and 2008 inclusive. Concentrations for CB and PBDEs were significantly higher in the Aberdeen Breakwater mussels than for all other sites. Concentrations at all sites were low with many congeners being below the detection limits for both contaminant groups. No seasonal trends were observed in the CBs or PBDE concentrations or composition at any of the five sites. The green-red transition (described by the EACpassive) was exceeded for CB118 in mussels from Aberdeen Breakwater and surprisingly at the pristine site of Loch Etive. As such both sites were classed as 'red'. All other ICES7 CBs were below EACs and therefore classed as 'blue' or 'green'.
Thyroid cell lines in research on goitrogenesis.
Gerber, H; Peter, H J; Asmis, L; Studer, H
1991-12-01
Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes.
NASA Astrophysics Data System (ADS)
Sinha, Rileen; Winer, Andrew G.; Chevinsky, Michael; Jakubowski, Christopher; Chen, Ying-Bei; Dong, Yiyu; Tickoo, Satish K.; Reuter, Victor E.; Russo, Paul; Coleman, Jonathan A.; Sander, Chris; Hsieh, James J.; Hakimi, A. Ari
2017-05-01
The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines.
Gyrate erythema in the setting of tinea pedis.
Myers, Kathryn; Terushkin, Vitaly; Meehan, Shane A; Cohen, David E
2016-12-15
Gyrate erythema, which also is known as erythemaannulare centrifugum (EAC), is a reactive dermatitisthat is thought to occur in response to an underlyingtrigger. The superficial form is characterized bythe typical, centrifugally-expanding, annular,erythematous patches or plaques with a distincttrailing scale. The deep form also is a centrifugallyexpanding,erythematous plaque but with induratedborders and absence of scale. These cutaneousfindings are thought to be reactive, most often inresponse to infections or drugs and, less likely, tounderlying malignant conditions.
2014-02-13
international trade and investment. From 2001 through 2011, Sub-Saharan Africa possessed four out of the world’s ten quickest growing economies . By 2007...together to largely encompass the geography of the future East African Community ( EAC ) REC. While colonial administrators leveraged regionalism to ease...emerging African nations had a “sparse population, small internal market, limited infrastructure, new and fragile borders, economies vulnerable to
2015-03-26
acquisition programs’ cost and schedule. Many prior studies have focused on the overall cost of programs (the cost estimate at completion (EAC)) ( Smoker ...regression ( Smoker , 2011), the Kalman Filter Forecasting Method (Kim, 2007), and analysis of the Integrated Master Schedule (IMS). All of the...A study by Smoker demonstrated this technique by first regressing the BCWP against months and the same approach for BAC (2011). In that study
Using Predictive Analytics to Detect Major Problems in Department of Defense Acquisition Programs
2012-03-01
research is focused on three questions. First, can we predict the contractor provided estimate at complete (EAC)? Second, can we use those predictions to...develop an algorithm to determine if a problem will occur in an acquisition program or sub-program? Lastly, can we provide the probability of a problem...more than doubling the probability of a problem occurrence compared to current tools in the cost community. Though program managers can use this
Meinhardt, J P; Ashton, B A; Annich, G M; Quintel, M; Hirschl, R B
2003-05-30
To evaluate the influence of pump system and flow pattern on expiratory airway collapse (EAC) in total perfluorocarbon ventilation. - Prospective, controlled, randomized animal trial for determination of (1) post-mortem changes by repeated expiration procedures (EP) with a constant flow piston pump (PP) before and after sacrifice (n = 8 rabbits), (2) differences between pump systems by subjecting animals to both PP and roller pump (RP) circuits for expiration (n = 16 rabbits). EP were performed using a servo-controlled shut-off at airway pressures < 25 cm H subset 2O randomly with either pump at different flows. - Expired volumes before and after sacrifice were not significantly different. PP and RP revealed identical mean flows, while significantly more liquid was drained using PP (p<0.05). Increasing differences towards higher flow rates indicated profound flow pulsatility in RP. - (1) post-mortem changes in expired volumes are not significant, (2) EAC is related to flow rate and pump system; (3) relationship between expiratory flow rate and drainable liquid volume is linear inverse; (4) PP provides higher drainage than RP. - Expiratory airway collapse is related to flow rate and pump system, post mortem changes in expirable volumes are not significant. Relationship between expiratory flow rate and drainable liquid volume is linear inverse, piston pump expiration provides higher drainage volumes than roller pump expiration.
Ju, Young-Ho; Park, Euyhyun; Park, Sangheon; Jung, Kwangjin; Lee, Kijeong; Im, Gi Jung
2014-03-01
The extent of inferior displacement of the mastoid tegmen is related to the severity of congenital aural atresia (CAA). To analyze anatomic variations observed on high-resolution temporal bone computed tomography (TBCT) in patients with CAA, the extent of inferior displacement of the mastoid tegmen and the size of the incudo-stapedial (IS) joint angle were compared with surgical parameters for atresiaplasty, such as Jahrsdoerfer score and hearing acuity. Sixty-one patients with unilateral CAA underwent high-resolution TBCT and hearing tests. We evaluated TBCTs in terms of Jahrsdoerfer criteria and analyzed the relationships among the inferior displacement of the mastoid tegmen, size of the IS joint angle, hearing acuity, and the Jahrsdoerfer score on the atretic side. IS joint angle on the atretic side was found to be 120.6 ± 11°, which was significantly greater than the corresponding value of 103.4 ± 5.4° on the normal side. Cholesteatoma occurred significantly more often in CAA patients with narrow external auditory canals (EACs) (9/27; 33.3%), compared with CAA patients with no EAC opening (2/34; 5.9%). There was a significant relation between the extent of inferior displacement of the mastoid tegmen (28.9% in the atretic side and 17.3% in the normal side) and the Jahrsdoerfer score (p < 0.0001).
Congenital Auricular Malformations: Description of Anomalies and Syndromes.
Bartel-Friedrich, Sylva
2015-12-01
Half of the malformations in the ear, nose, and throat region affect the ear. Malformations of the external ear (pinna or auricle with external auditory canal [EAC]) are collectively termed microtia. Microtia is a congenital anomaly that ranges in severity from mild structural abnormalities to complete absence of the external ear (anotia). Microtia occurs more frequently in males (∼2 or 3:1), is predominantly unilateral (∼70-90%), and more often involves the right ear (∼60%). The reported prevalence varies geographically from 0.83 to 17.4 per 10,000 births. Microtia may be genetic (with family history, spontaneous mutations) or acquired. Malformations of the external ear can also involve the middle ear and/or inner ear. Microtia may be an isolated birth defect, but associated anomalies or syndromes are described in 20 to 60% of cases, depending on study design. These generally fit within the oculo-auriculo-vertebral spectrum; defects are located most frequently in the facial skeleton, facial soft tissues, heart, and vertebral column, or comprise a syndrome (e.g., Treacher Collins syndrome). Diagnostic investigation of microtia includes clinical examination, audiologic testing, genetic analysis and, especially in higher grade malformations with EAC deformities, computed tomography (CT) or cone-beam CT for the planning of surgery and rehabilitation procedures, including implantation of hearing aids. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Leedale, Joseph; Tompkins, Adrian M; Caminade, Cyril; Jones, Anne E; Nikulin, Grigory; Morse, Andrew P
2016-03-31
The effect of climate change on the spatiotemporal dynamics of malaria transmission is studied using an unprecedented ensemble of climate projections, employing three diverse bias correction and downscaling techniques, in order to partially account for uncertainty in climate- driven malaria projections. These large climate ensembles drive two dynamical and spatially explicit epidemiological malaria models to provide future hazard projections for the focus region of eastern Africa. While the two malaria models produce very distinct transmission patterns for the recent climate, their response to future climate change is similar in terms of sign and spatial distribution, with malaria transmission moving to higher altitudes in the East African Community (EAC) region, while transmission reduces in lowland, marginal transmission zones such as South Sudan. The climate model ensemble generally projects warmer and wetter conditions over EAC. The simulated malaria response appears to be driven by temperature rather than precipitation effects. This reduces the uncertainty due to the climate models, as precipitation trends in tropical regions are very diverse, projecting both drier and wetter conditions with the current state-of-the-art climate model ensemble. The magnitude of the projected changes differed considerably between the two dynamical malaria models, with one much more sensitive to climate change, highlighting that uncertainty in the malaria projections is also associated with the disease modelling approach.
Gain affected by the interior shape of the ear canal.
Yu, Jen-Fang; Chen, Yen-Sheng; Cheng, Wei-De
2011-06-01
This study investigated the correlation of gain distribution and the interior shape of the human external ear canal. Cross-sectional study of gain measurement at the first bend and second bend. Chang Gung Memorial Hospital and Chang Gung University. There were 15 ears in patients aged between 20 and 30 years (8 men/7 women) with normal hearing and middle ears. Stimulus frequencies of 500, 1000, 2000, 3000, and 4000 Hz were based on the standard clinical hearing test. Measurements closer to the tympanic membrane and the positions at the first and second bends were confirmed by using otoscope. Real ear measurement to analyze the canal resonance in human external ears was adopted. This study found that gain at stimulus frequencies of 4000 Hz was affected by the interior shape of the ear canal (P < .005), particularly at the first and second bends, whereas gain was only affected by the length of the ear canal for stimulus frequencies of 2000 Hz (P < .005). This study found that gain was affected not only by the length of the external auditory canal (EAC) but also by the interior shape of the EAC significantly. The findings of this study may have potential clinical applications in canalplasty and congenital aural atresia surgery and may be used to guide surgeries that attempt to reshape the ear canal to achieve more desirable hearing outcomes.
In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments.
Kasinathan, Narayanan; Amirthalingam, Muthukumar; Reddy, Neetinkumar D; Jagani, Hitesh V; Volety, Subrahmanyam M; Rao, Josyula Venkata
2016-01-01
Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes. To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN). In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer. The effect of independent variables was studied in two stages. First, the effect of drug-polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500 nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release. This implant could be further evaluated for pharmacological activities.
NASA Astrophysics Data System (ADS)
Rykova, Tatiana; Oke, Peter R.; Griffin, David A.
2017-06-01
Using output from a near-global eddy-resolving ocean model, we analyse the properties and characteristics of quasi-isotropic eddies in five Western Boundary Current (WBC) regions, including the extensions of the Agulhas, East Australian Current (EAC), Brazil-Malvinas Confluence (BMC), Kuroshio and Gulf Stream regions. We assess the model eddies by comparing to satellite and in situ observations, and show that most aspects of the model's representation of eddies are realistic. We find that the mean eddies differ dramatically between these WBC regions - all with some unique and noteworthy characteristics. We find that the vertical displacement of isopycnals of Agulhas eddies is the greatest, averaging 350-450 m at depths of over 800-900 m. EAC (BMC) eddies are the least (most) barotropic, with only 50% (85-90%) of the velocity associated with the barotropic mode. Kuroshio eddies are the most stratified, resulting in small isopycnal displacement, even for strong eddies; and Gulf Stream eddies carry the most heat. Despite their differences, we explicitly show that the source waters for anticyclonic eddies are a mix of the WBC water (from the boundary current itself) and water that originates equatorward of the WBC eddy-field; and cyclonic eddies are a mix of WBC water and water that originates poleward of the WBC eddy-field.
Evaluating cell lines as tumour models by comparison of genomic profiles
Domcke, Silvia; Sinha, Rileen; Levine, Douglas A.; Sander, Chris; Schultz, Nikolaus
2013-01-01
Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types. PMID:23839242
Continuous hematopoietic cell lines as model systems for leukemia-lymphoma research.
Drexler, H G; Matsuo, A Y; MacLeod, R A
2000-11-01
Along with other improvements, the advent of continuous human leukemia-lymphoma (LL) cell lines as a rich resource of abundant, accessible and manipulable living cells has contributed significantly to a better understanding of the pathophysiology of hematopoietic tumors. The first LL cell lines, Burkitt's lymphoma-derived lines, were established in 1963. Since then, more than 1000 cell lines have been described, although not all of them in full detail. The major advantages of continuous cell lines is the unlimited supply and worldwide availability of identical cell material, and the infinite viable storability in liquid nitrogen. LL cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro under preservation of most cellular features, and specific genetic alterations. The most practical classification of LL cell lines assigns them to one of the physiologically occurring cell lineages, based on their immunophenotype, genotype and functional features. Truly malignant cell lines must be discerned from Epstein-Barr virus (EBV)-immortalized normal cells, using various distinguishing parameters. However, the picture is not quite so straightforward, as some types of LL cell lines are indeed EBV+, and some EBV+ normal cell lines carry also genetic aberrations and may mimic malignancy-associated features. Apart from EBV and human T-cell leukemia virus in some lines, the majority of wild-type LL cell lines are virus-negative. The efficiency of cell line establishment is rather low and the deliberate establishment of new LL cell lines remains by and large an unpredictable random process. Difficulties in establishing continuous cell lines may be caused by the inappropriate selection of nutrients and growth factors for these cells. Clearly, a generally suitable microenvironment for hematopoietic cells, either malignant or normal, cannot yet be created in vitro. The characterization and publication of new LL cell lines should provide important and informative core data, attesting to their scientific significance. Large percentages of LL cell lines are contaminated with mycoplasma (about 30%) or are cross-contaminated with other cell lines (about 15-20%). Solutions to these problems are sensitive detection, effective elimination and rigorous prevention of mycoplasma infection, and proper, regular authentication of cell lines. The underlying cause, however, appears to be negligent cell culture practice. The willingness of investigators to make their LL cell lines available to others is all too often limited. There is a need in the scientific community for clean and authenticated high-quality LL cell lines to which every scientist has access. These are offered by various institutionalized public cell line banks. It has been argued that LL cell lines are genetically unstable (both cytogenetically and molecular genetically). For instance, cell lines are supposed to acquire numerical and structural chromosomal alterations and various types of mutations (e.g. point mutations) in vitro. We present evidence that while nearly 100% of all LL cell lines indeed carry genetic alterations, these alterations appear to be stable rather than unstable. As an example of the practical utility of LL cell lines, the recent advances in studies of classical and molecular cytogenetics, which in large part were made possible by cell lines, are highlighted. A list of the most useful, robust and publicly available reference cell lines that may be used for a variety of experimental purposes is proposed. Clearly, by opening new avenues for investigation, studies of LL cell lines have provided seminal insights into the biology of hematopoietic neoplasia. Over a period of nearly four decades, these initially rather exotic cell cultures, known only to a few specialists, have become ubiquitous powerful research tools that are available to every investigator.
Ong, Edison; Xie, Jiangan; Ni, Zhaohui; Liu, Qingping; Sarntivijai, Sirarat; Lin, Yu; Cooper, Daniel; Terryn, Raymond; Stathias, Vasileios; Chung, Caty; Schürer, Stephan; He, Yongqun
2017-12-21
Aiming to understand cellular responses to different perturbations, the NIH Common Fund Library of Integrated Network-based Cellular Signatures (LINCS) program involves many institutes and laboratories working on over a thousand cell lines. The community-based Cell Line Ontology (CLO) is selected as the default ontology for LINCS cell line representation and integration. CLO has consistently represented all 1097 LINCS cell lines and included information extracted from the LINCS Data Portal and ChEMBL. Using MCF 10A cell line cells as an example, we demonstrated how to ontologically model LINCS cellular signatures such as their non-tumorigenic epithelial cell type, three-dimensional growth, latrunculin-A-induced actin depolymerization and apoptosis, and cell line transfection. A CLO subset view of LINCS cell lines, named LINCS-CLOview, was generated to support systematic LINCS cell line analysis and queries. In summary, LINCS cell lines are currently associated with 43 cell types, 131 tissues and organs, and 121 cancer types. The LINCS-CLO view information can be queried using SPARQL scripts. CLO was used to support ontological representation, integration, and analysis of over a thousand LINCS cell line cells and their cellular responses.
Uchio-Yamada, Kozue; Kasai, Fumio; Ozawa, Midori; Kohara, Arihiro
2017-03-01
Misidentification or cross-contamination of cell lines can cause serious issues. Human cell lines have been authenticated by short tandem repeat profiling; however, mouse cell lines have not been adequately assessed. In this study, mouse cell lines registered with the JCRB cell bank were examined by simple sequence length polymorphism (SSLP) analysis to identify their strains. Based on comparisons with 7 major inbred strains, our results revealed their strains in 80 of 90 cell lines. However, 12 of the 80 cell lines (15%) were found to differ from registered information. Of them, 4 cell lines originated from the same mouse, which had been generated through mating between two different inbred strains. The genotype of the mouse sample had not been examined after the backcross, leading to strain misidentification in those cell lines. Although 8 other cell lines had been established as sublines of a BALB/c cell line, their SSLP profiles are similar to a Swiss cell line. This affects differences in genotypes between inbred and outbred strains. Because the use of inbred samples and interbreeding between strains are not involved in human materials, our results suggest that the cause and influence of misidentification in mouse cell lines are different from those in human.
Establishment and characterization of three immortal bovine muscular epithelial cell lines.
Jin, Xun; Lee, Joong-Seob; Kwak, Sungwook; Lee, Soo-Yeon; Jung, Ji-Eun; Kim, Tae-Kyung; Xu, Chenxiong; Hong, Zhongshan; Li, Zhehu; Kim, Sun-Myung; Pian, Xumin; Lee, Dong-Hee; Yoon, Jong-Taek; You, Seungkwon; Choi, Yun-Jaie; Kim, Huunggee
2006-02-28
We have established three immortal bovine muscular epithelial (BME) cell lines, one spontaneously immortalized (BMES), the second SV40LT-mediated (BMEV) and the third hTERT-mediated (BMET). The morphology of the three immortal cell lines was similar to that of early passage primary BME cells. Each of the immortal cell lines made cytokeratin, a typical epithelial marker. BMET grew faster than the other immortal lines and the BME cells, in 10% FBS-DMEM medium, whereas neither the primary cells nor the three immortal cell lines grew in 0.5% FBS-DMEM. The primary BME cells and the immortal cell lines, with the exception of BMES, made increasing amounts of p53 protein when treated with doxorubicin, a DNA damaging agent. On the other hand, almost half of the cells in populations of the three immortal cell lines may lack p16(INK4a) regulatory function, compared to primary BME cells that were growth arrested by enforced expression of p16(INK4a). In soft-agar assays, the primary cells and immortal cell lines proved to be less transformed in phenotype than HeLa cells. The three immortal epithelial-type cell lines reported here are the first cell lines established from muscle tissue of bovine or other species.
GursesCila, Hacer E; Acar, Muradiye; Barut, Furkan B; Gunduz, Mehmet; Grenman, Reidar; Gunduz, Esra
2016-12-01
Recent studies have shown that cancer stem cells are resistant to chemotherapy. The aim of this study was to compare RIF1 gene expression in head and neck, pancreatic cancer and glioma cell lines and the cancer stem cells isolated from these cell lines. UT-SCC-74 from Turku University and UT-SCC-74B primary tumor metastasis and neck cancer cell lines, YKG-1 glioma cancer cell line from RIKEN, pancreatic cancer cell lines and ASPC-1 cells from ATCC were grown in cell culture. To isolate cancer stem cells, ALDH-1 for UT-SCC-74 and UT-SCC-74B cell line, CD-133 for YKG-1 cell line and CD-24 for ASPC-1 cell line, were used as markers of cancer stem cells. RNA isolation was performed for both cancer lines and cancer stem cells. RNAs were converted to cDNA. RIF1 gene expression was performed by qRT-PCR analysis. RIF1 gene expression was compared with cancer cell lines and cancer stem cells isolated from these cell lines. The possible effect of RIF1 gene was evaluated. In the pancreatic cells, RIF1 gene expression in the stem cell-positive cell line was 256 time that seen in the stem cell-negative cell line. Considering the importance of RIF1 in NHEJ and of NHEJ in pancreatic cancer, RIF1 may be one of the genes that plays an important role in the diagnoses and therapeutic treatment of pancreatic cancer. The results of head and neck and brain cancers are inconclusive and further studies are required to elucidate the connection between RIF1 gene and these other types of cancers.
Mix-ups and mycoplasma: the enemies within.
Drexler, Hans G; Uphoff, Cord C; Dirks, Willy G; MacLeod, Roderick A F
2002-04-01
Human leukemia-lymphoma (LL) cell lines represent important tools for experimental research. Among the various problems associated with cell lines, the two most common concern contaminations: (1) cross-contamination with unrelated cells and (2) contamination with microorganisms, in particular mycoplasma. The bad news is that about one-third of the cell lines are either cross-contaminated or mycoplasma-infected or both. The good news is that there are means to recognize and overcome these problems. In cases where, during attempts to establish new LL cell lines, primary LL cultures are cross-contaminated with continuous cell lines, intended new cell lines simply cannot be established ("early" cross-contamination). In cases of "late" cross-contamination of existing LL cell lines where the intrusive cells have a growth advantage, the original ("uncontaminated") cell lines may still be available elsewhere. DNA fingerprinting and cytogenetic analysis appear to be the most suitable approaches to detect cross-contaminations and to authenticate LL cell lines. A different but related aspect of "false" LL cell lines is the frequent misclassification of cell lines whereby the actual cell type of the cell line does not correspond to the purported model character of the cell line. Mycoplasma infection can have a multitude of effects on the eukaryotic cells which, due to the variety of infecting mycoplasma species and many other contributing parameters, cannot be predicted, rendering resulting data questionable at best. Practical procedures for the detection and elimination of mycoplasma contamination have been developed. Diagnostic and preventive strategies in order to hem the alarming increase in "false" and mycoplasma-positive LL cell lines are recommended.
USDA-ARS?s Scientific Manuscript database
The adaptation to feeder-independent growth of a pig embryonic stem cell-derived pancreatic cell line is described. The parental PICM-31 cell line, previously characterized as an exocrine pancreas cell line, was colony-cloned two times in succession resulting in the subclonal cell line, PICM-31A1. P...
2013-10-01
cell lines, such as cervix cancer cell line (HeLa) and breast cancer cell line (MDA-MB-231), were also employed. The experiments with other cell lines...breast cancer cell line (MDA-MB- 231), and cervix cancer cell line (HeLa). Different from our hypothesis, prostate cancer cell lines did not present...Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model PRINCIPAL INVESTIGATOR: Kwang Song
[The factors involved in invasive ability of endometrial carcinoma cells].
Mori, Y; Mizuuchi, H; Sato, K; Okamura, N; Kudo, R
1994-06-01
The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.
McDermott, Martina; Eustace, Alex J.; Busschots, Steven; Breen, Laura; Crown, John; Clynes, Martin; O’Donovan, Norma; Stordal, Britta
2014-01-01
The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance. PMID:24639951
Tsutsui, Takeki; Kumakura, Shin-Ichi; Tamura, Yukiko; Tsutsui, Takeo W; Sekiguchi, Mizuki; Higuchi, Tokihiro; Barrett, J Carl
2003-05-01
Five immortal cell lines derived from a Li-Fraumeni syndrome patient (MDAH 087) with a germline mutant p53 allele were characterized with respect to telomere length and genomic instability. The remaining wild-type p53 allele is lost in the cell lines. Telomerase activity was undetectable in all immortal cell lines. Five subclones of each cell line and five re-subclones of each of the subclones also showed undetectable telomerase activity. All five immortal cell lines exhibited variability in the mean length of terminal restriction fragments (TRFs). Subclones of each cell line, and re-subclones of the subclones also showed TRF variability, indicating that the variability is owing to clonal heterogeneity. Chromosome aberrations were observed at high frequencies in these cell lines including the subclones and re-subclones, and the principal types of aberrations were breaks, double minute chromosomes and dicentric chromosomes. In addition, minisatellite instability detected by DNA fingerprints was observed in the immortal cell lines. However, all of the cell lines were negative for microsatellite instability. As minisatellite sequences are considered recombinogenic in mammalian cells, these results suggest that recombination rates can be increased in these cell lines. Tumor-derived human cell lines, HT1080 cells and HeLa cells that also lack p53 function, exhibited little genomic instability involving chromosomal and minisatellite instabilities, indicating that chromosomal and minisatellite instabilities observed in the immortal cell lines lacking telomerase activity could not result from loss of p53 function.
Lee, Suk Kyoo; Lee, Gyun Min
2003-06-30
Apoptosis-resistant dihydrofolate reductase-deficient CHO cell line (dhfr(-) CHO-bcl2) was developed by introduction of the bcl-2 gene into the dhfr(-) CHO cell line (DUKX-B11, ATCC CRL-9096) and subsequent selection of clones stably overexpressing Bcl-2 in the absence of selection pressure. When the dhfr(-) CHO-bcl2 cell line was used as a host cell line for development of a recombinant CHO (rCHO) cell line expressing a humanized antibody, it displayed stable expression of the bcl-2 gene during rCHO cell line development and no detrimental effect of Bcl-2 overexpression on specific antibody productivity. Taken together, the results obtained demonstrate that the use of an apoptosis-resistant dhfr(-) CHO cell line as the host cell line saves the effort of establishing an apoptosis-resistant rCHO cell line and expedites the development process of apoptosis-resistant rCHO cells producing therapeutic proteins. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 872-876, 2003.
NASA Expendable Launch Vehicle (ELV) Payload Safety Review Process
NASA Technical Reports Server (NTRS)
Starbus, Calvert S.; Donovan, Shawn; Dook, Mike; Palo, Tom
2007-01-01
Issues addressed by this program: (1) Complicated roles and responsibilities associated with multi-partner projects (2) Working relationships and communications between all organizations involved in the payload safety process (3) Consistent interpretation and implementation of safety requirements from one project to the rest (4) Consistent implementation of the Tailoring Process (5) Clearly defined NASA decision-making-authority (6) Bring Agency-wide perspective to each ElV payload project. Current process requires a Payload Safety Working Group (PSWG) for eac payload with representatives from all involved organizations.
1974-12-01
as a series of sections, eacN represent- ing one pressure and each preceding the corresponding pressure group of the sur- face thermochemistry deck...groups together make up the surface thermochemistry deck. Within each pressure group the transfer coefficient values will be ordered. Within each transfer...values in each pressure group may not exceed 5 but may be only 1. If no kinetics effects are to be considered a transfer coefficient of zero is acceptable
1990-06-01
plants or for the expansion of existing firms. Services, explains that what attracted the company Reprinted with the permission of Area Develop- ment...upgrade the park’s appearance and to expand pany. Mr. Hayworth adds that the company had a water pressure for the plant sprinkler system. 26 difficult time...and Aviation Uses: Office indus- as the permanent staff for the Committee. trial parks or plants have been established at 75 of The EAC works with
Solvent Effects in the Electroreduction of Ferrocene at Pt in the Temperature Range 200-300 K
1991-03-20
been obtained at iow temperatures downto 92 K ata P ulramcroeectode(dimete, 2 pm inthree alcohol solvents, namely, methanol, ethanol , and n-propanol. In...In this aree.-doutee-eace&4 Kinetic parameters for the electrooxidation of ferrocene have been obtained at low temperatures down to 193 ’K at a Pt...with solvent nature. tnsvetsiky of~aitm Davis, CA 95616 Kinetic data obtained in mteehanol, ethanol . and I1- propanol as a function of temperature
Leukemia-lymphoma cell lines as model systems for hematopoietic research.
Drexler, Hans G; MacLeod, Roderick A F
2003-01-01
Continuous human leukemia-lymphoma (LL) cell lines comprise a rich self-renewing resource of accessible and manipulable living cells which has illuminated the pathophysiology of hematopoietic tumors as well as basic cell biology. The major key advantages of continuous cell lines are the unlimited supply and worldwide availability of identical cell material and their cryopreservation. LL cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro with preservation of most cellular features, and specific genetic alterations. The most practical classification of LL cell lines assigns them to one of the physiologically occurring cell lineages, based on their immunophenotype, genotype and functional features. Truly malignant cell lines may be distinguished from Epstein-Barr virus (EBV)-immortalized normal cells, using various operational and conceptual parameters. The characterization and publication of new LL cell lines provides important and informative core data which, by opening new avenues for investigation, have become ubiquitous powerful research tools that are available to every investigator by reference cell repositories. There is a need in the scientific community for clean and authenticated LL cell lines to which every scientist has access as offered by these institutionalized public cell line banks. A list of the most useful, robust and freely available reference cell lines is proposed in this review. Clearly, studies of LL cell lines have provided seminal insights into the biology of hematopoietic neoplasia.
[Establishment of human embryonic stem cell lines and their therapeutic application].
Suemori, Hirofumi
2004-03-01
Embryonic stem (ES) cell lines are pluripotent stem cell lines that can be propagated indefinitely in culture, retaining their potency to differentiate into every type of cell and tissue in the body. ES cell lines were first established from mouse blastocysts, and have been used for research in developmental biology. ES cells have been proven to be very valuable in the genetic modification of the mouse, especially in producing knockout mice. Since establishment of human ES cell lines was reported, their use in cell replacement therapies has been enthusiastically expected. There have been reports of the differentiation of several useful cell types from human ES cell lines, and clinical use of functional tissues and cells from human ES cells is anticipated. In Japan, there have also been many demands for the use of human ES cells in basic and pre-clinical research. We obtained governmental permission to establish human ES cell lines in April 2002 and started research using donated frozen embryos in January 2003. We successfully established three ES cell line from three blastocysts. These cell lines will be distributed at cost to researchers who have governmental permission to use human ES cells.
Chandipura virus growth kinetics in vertebrate cell lines, insect cell lines & embryonated eggs.
Jadi, R S; Sudeep, A B; Kumar, Satyendra; Arankalle, V A; Mishra, A C
2010-08-01
Since not much information on Chandipura virus is available, an attempt was made to study the growth kinetics of the virus in certain vertebrate, invertebrate cell lines and embryonated chicken eggs. Comparative study of Chandipura virus (CHPV) growth kinetics in three vertebrate cell lines [Vero E6, Rhabdo myosarcoma (RD), Porcine stable kidney (PS) cell lines], two insect cell lines [Aedes aegypti (AA) and Phlebotomus papatasi (PP-9) cell lines] and embryonated pathogen free chicken eggs was conducted, by tissue culture infective dose 50 per cent (TCID(50)) and indirect immunofluorescence assay (IFA). All the cell lines and embryonated egg supported the growth of CHPV and yielded high virus titre. The vertebrate cell lines showed distinct cytopathic effect (CPE) within 4-6 h post infection (PI), while no CPE was observed in insect cell lines. PP-9 cell line was the most sensitive system to CHPV as viral antigen could be detected at 1 h PI by IFA. Our results demonstrated that all the systems were susceptible to CHPV and achieved high yield of virus. However, the PP-9 cell line had an edge over the others due to its high sensitivity to the virus which might be useful for detection and isolation of the virus during epidemics.
Drexler, H G; Matsuo, Y
2000-05-01
Malignancies involving natural killer (NK) cells are rare disorders. The complexity of NK cell-involving disorders has only recently been appreciated. Modern classifications discern immature (precursor) from mature NK cell leukemias-lymphomas. Continuous NK leukemia-lymphoma cell lines represent important model systems to study these neoplasms. While there are a number of putative NK cell lines which are, however, either not characterized, not immortalized, non-malignant, non-NK, or plain false cell lines, six bona fide malignant NK cell lines have been established and are sufficiently well characterized: HANK1, KHYG-1, NK-92, NKL, NK-YS and YT. Except for YT which was derived from a not further defined acute lymphoblastic lymphoma, these cell lines were established from patients with various NK cell malignancies. Five of the six cell lines are constitutively interleukin-2-dependent. Their immunoprofile is remarkably similar: CD1-, CD2+, surface CD3 (but cytoplasmic CD3epsilon+), CD4-, CD5-, CD7+, CD8-, CD16-, CD56+, CD57-, TCRalphabeta-, TCRgammadelta-, negative for B cell and myelomonocytic markers. The immunoglobulin heavy chain and T cell receptor genes are all in germline configuration. All six lines show complex chromosomal alterations, with both numerical and structural aberrations, attesting to their malignant and monoclonal nature. Functionally, these cells which contain azurophilic granules in their cytoplasm are nearly universally positive in NK activity assays. Three of five cell lines are Epstein-Barr virus-positive (type II latency). The composite data on these six cell lines allow for the operational definition of a typical malignant NK cell line profile. NK leukemia-lymphoma cell lines will prove invaluable for studies of normal and malignant NK cell biology.
Shi, Cheng; Shen, Huan; Jiang, Wei; Song, Zhi-Hua; Wang, Cheng-Yan; Wei, Li-Hui
2011-04-01
Human embryonic stem cells have prospective uses in regenerative medicine and drug screening. Every human embryonic stem cell line has its own genetic background, which determines its specific ability for differentiation as well as susceptibility to drugs. It is necessary to compile many human embryonic stem cell lines with various backgrounds for future clinical use, especially in China due to its large population. This study contributes to isolating new Chinese human embryonic stem cell lines with clarified directly differentiation ability. Donated embryos that exceeded clinical use in our in vitro fertilization-embryo transfer (IVF-ET) center were collected to establish human embryonic stem cells lines with informed consent. The classic growth factors of basic fibroblast growth factor (bFGF) and recombinant human leukaemia inhibitory factor (hLIF) for culturing embryonic stem cells were used to capture the stem cells from the plated embryos. Mechanical and enzymetic methods were used to propagate the newly established human embryonic stem cells line. The new cell line was checked for pluripotent characteristics with detecting the expression of stemness genes and observing spontaneous differentiation both in vitro and in vivo. Finally similar step-wise protocols from definitive endoderm to target specific cells were used to check the cell line's ability to directly differentiate into pancreatic and hepatic cells. We generated a new Chinese human embryonic stem cells line, CH1. This cell line showed the same characteristics as other reported Chinese human embryonic stem cells lines: normal morphology, karyotype and pluripotency in vitro and in vivo. The CH1 cells could be directly differentiated towards pancreatic and hepatic cells with equal efficiency compared to the H1 cell line. This newly established Chinese cell line, CH1, which is pluripotent and has high potential to differentiate into pancreatic and hepatic cells, will provide a useful tool for embryo development research, along with clinical treatments for diabetes and some hepatic diseases.
77 FR 5489 - Identification of Human Cell Lines Project
Federal Register 2010, 2011, 2012, 2013, 2014
2012-02-03
...-01] Identification of Human Cell Lines Project AGENCY: National Institute of Standards and Technology... cell line samples as part of the Identification of Human Cell Lines Project. All data and corresponding... cell lines accepted on the NIST Applied Genetics Group Web site at http://www.nist.gov/mml/biochemical...
Parameswaran, V; Ishaq Ahmed, V P; Shukla, Ravi; Bhonde, R R; Sahul Hameed, A S
2007-01-01
Two new cell lines, SIMH and SIGE, were derived from the heart of milkfish (Chanos chanos), a euryhaline teleost, and from the eye of grouper (Epinephelus coioides), respectively. These cell lines were maintained in Leibovitz's L-15 supplemented with 20% fetal bovine serum (FBS). The SIMH cell line was subcultured more than 50 times over a period of 210 days and SIGE cell line has been subcultured 100 times over a period of 1 1/2 years. The SIMH cell line consists predominantly of fibroblastic-like cells. The SIGE cell line consists predominantly of epithelial cells. Both the cell lines were able to grow at temperatures between 25 and 32 degrees C with an optimum temperature of 28 degrees C. The growth rate of these cells increased as the proportion of FBS increased from 2% to 20% at 28 degrees C with optimum growth at the concentrations of 15% or 20% FBS. Seven marine fish viruses were tested to determine the susceptibility of these cell lines. The SIGE cell line was found to be susceptible to nodavirus, MABV NC-1 and Y6, and the infection was confirmed by cytopathic effect (CPE) and reverse transcriptase-polymerase chain reaction. When these cells were transfected with pEGFP-N1 vector DNA, significant fluorescent signals were observed, suggesting that these cell lines can be a useful tool for transgenic and genetic manipulation studies. Further, these cell lines are characterized by immunocytochemistry using confocal laser scanning microscopy (CFLSM).
Korch, Christopher; Hall, Erin M.; Dirks, Wilhelm G.; Ewing, Margaret; Faries, Mark; Varella‐Garcia, Marileila; Robinson, Steven; Storts, Douglas; Turner, Jacqueline A.; Wang, Ying; Burnett, Edward C.; Healy, Lyn; Kniss, Douglas; Neve, Richard M.; Nims, Raymond W.; Reid, Yvonne A.; Robinson, William A.
2017-01-01
A variety of analytical approaches have indicated that melanoma cell line UCLA‐SO‐M14 (M14) and breast carcinoma cell line MDA‐MB‐435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross‐contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA‐MB‐435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA‐MB‐435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA‐MB‐435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA‐MB‐435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research. PMID:28940260
Povey, Jane F; O'Malley, Christopher J; Root, Tracy; Martin, Elaine B; Montague, Gary A; Feary, Marc; Trim, Carol; Lang, Dietmar A; Alldread, Richard; Racher, Andrew J; Smales, C Mark
2014-08-20
Despite many advances in the generation of high producing recombinant mammalian cell lines over the last few decades, cell line selection and development is often slowed by the inability to predict a cell line's phenotypic characteristics (e.g. growth or recombinant protein productivity) at larger scale (large volume bioreactors) using data from early cell line construction at small culture scale. Here we describe the development of an intact cell MALDI-ToF mass spectrometry fingerprinting method for mammalian cells early in the cell line construction process whereby the resulting mass spectrometry data are used to predict the phenotype of mammalian cell lines at larger culture scale using a Partial Least Squares Discriminant Analysis (PLS-DA) model. Using MALDI-ToF mass spectrometry, a library of mass spectrometry fingerprints was generated for individual cell lines at the 96 deep well plate stage of cell line development. The growth and productivity of these cell lines were evaluated in a 10L bioreactor model of Lonza's large-scale (up to 20,000L) fed-batch cell culture processes. Using the mass spectrometry information at the 96 deep well plate stage and phenotype information at the 10L bioreactor scale a PLS-DA model was developed to predict the productivity of unknown cell lines at the 10L scale based upon their MALDI-ToF fingerprint at the 96 deep well plate scale. This approach provides the basis for the very early prediction of cell lines' performance in cGMP manufacturing-scale bioreactors and the foundation for methods and models for predicting other mammalian cell phenotypes from rapid, intact-cell mass spectrometry based measurements. Copyright © 2014 Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Medina, D.; Oborn, C.J.; Li, M.L.
1987-09-01
The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appearedmore » to represent myoepithelial cells. The cell lines were examined for expression of {beta}-casein mRNA in the presence or absence of prolactin. The inducibility of {beta}-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types.« less
Adventitious viruses in insect cell lines used for recombinant protein expression.
Geisler, Christoph; Jarvis, Donald L
2018-04-01
Insect cells are widely used for recombinant protein expression, typically as hosts for recombinant baculovirus vectors, but also for plasmid-mediated transient transfection or stable genetic transformation. Insect cells are used to express proteins for research, as well as to manufacture biologicals for human and veterinary medicine. Recently, several insect cell lines used for recombinant protein expression were found to be persistently infected with adventitious viruses. This has raised questions about how these infections might affect research performed using those cell lines. Furthermore, these findings raised serious concerns about the safety of biologicals produced using those cell lines. In response, new insect cell lines lacking adventitious viruses have been isolated for use as improved research tools and safer biological manufacturing platforms. Here, we review the scientific and patent literature on adventitious viruses found in insect cell lines, affected cell lines, and new virus-free cell lines. Copyright © 2017 Elsevier Inc. All rights reserved.
Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines.
Almanaa, Taghreed N; Geusz, Michael E; Jamasbi, Roudabeh J
2012-10-24
Many cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized. Cell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20-80 μM curcumin for 30 hrs. Cell lines surviving 40 or 60 μM curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-κB were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 μM curcumin to determine whether their sensitivity was different from the original lines. The cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 μM curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-κB and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity to curcumin when compared with the original lines. Our results suggest that curcumin not only eliminates cancer cells but also targets CSCs. Therefore, curcumin may be an effective compound for treating esophageal and possibly other cancers in which CSCs can cause tumor recurrence.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gestl, Erin E., E-mail: egestl@wcupa.edu; Anne Boettger, S., E-mail: aboettger@wcupa.edu
2012-06-29
Highlights: Black-Right-Pointing-Pointer Eight human colorectal cell lines were evaluated for p53 and mortalin localization. Black-Right-Pointing-Pointer Six cell lines displayed cytoplasmic sequestration of the tumor suppressor p53. Black-Right-Pointing-Pointer Direct interaction between mortalin and p53 was shown in five cell lines. Black-Right-Pointing-Pointer Cell lines positive for p53 sequestration yielded elevated p53 expression levels. Black-Right-Pointing-Pointer This study yields the first evidence of cytoplasmic sequestration p53 by mortalin. -- Abstract: While it is known that cytoplasmic retention of p53 occurs in many solid tumors, the mechanisms responsible for this retention have not been positively identified. Since heatshock proteins like mortalin have been associated withmore » p53 inactivation in other tumors, the current study sought to characterize this potential interaction in never before examined colorectal adenocarcinoma cell lines. Six cell lines, one with 3 different fractions, were examined to determine expression of p53 and mortalin and characterize their cellular localization. Most of these cell lines displayed punctate p53 and mortalin localization in the cell cytoplasm with the exception of HCT-8 and HCT116 379.2 cells, where p53 was not detected. Nuclear p53 was only observed in HCT-116 40-16, LS123, and HT-29 cell lines. Mortalin was only localized in the cytoplasm in all cell lines. Co-immunoprecipitation and immunohistochemistry revealed that p53 and mortalin were bound and co-localized in the cytoplasmic fraction of four cell lines, HCT-116 (40-16 and 386; parental and heterozygous fractions respectively of the same cell line), HT-29, LS123 and LoVo, implying that p53 nuclear function is limited in those cell lines by being restricted to the cytoplasm. Mortalin gene expression levels were higher than gene expression levels of p53 in all cell lines. Cell lines with cytoplasmic sequestration of p53, however, also displayed elevated p53 gene expression levels compared to cell lines without p53 sequestration. Our data reveal the characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas.« less
Development of a new canine osteosarcoma cell line.
Séguin, B; Zwerdling, T; McCallan, J L; DeCock, H E V; Dewe, L L; Naydan, D K; Young, A E; Bannasch, D L; Foreman, O; Kent, M S
2006-12-01
Establishing a canine osteosarcoma (OSA) cell line can be useful to develop in vivo and in vitro models of OSA. The goal of this study was to develop, characterize and authenticate a new canine OSA cell line and a clone. A cell line and a clone were developed with standard cell culture techniques from a naturally occurring OSA in a dog. The clonal cell line induced a tumour after injection in RAG 1-deficient mouse. Histology was consistent with OSA. The original tumour from the dog and the tumour induced in the mouse were both reactive with vimentin and osteonectin (ON). The parent cell line and clonal cell line were reactive with ON, osteocalcin and alkaline phosphatase. Loss of heterozygosity was found in the same three microsatellite markers in the parent and clonal cell lines, and the tumour tissue grown in the mouse.
Bock, Christoph; Kiskinis, Evangelos; Verstappen, Griet; Gu, Hongcang; Boulting, Gabriella; Smith, Zachary D.; Ziller, Michael; Croft, Gist F.; Amoroso, Mackenzie W.; Oakley, Derek H.; Gnirke, Andreas; Eggan, Kevin; Meissner, Alexander
2011-01-01
SUMMARY The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research. However, substantial variation has been reported among pluripotent cell lines, which could affect their utility and clinical safety. Such cell-line-specific differences must be better understood before one can confidently use embryonic stem (ES) or induced pluripotent stem (iPS) cells in translational research. Toward this goal we have established genome-wide reference maps of DNA methylation and gene expression for 20 previously derived human ES lines and 12 human iPS cell lines, and we have measured the in vitro differentiation propensity of these cell lines. This resource enabled us to assess the epigenetic and transcriptional similarity of ES and iPS cells and to predict the differentiation efficiency of individual cell lines. The combination of assays yields a scorecard for quick and comprehensive characterization of pluripotent cell lines. PMID:21295703
Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines
DOE Office of Scientific and Technical Information (OSTI.GOV)
Felthaus, O.; Department of Oral and Maxillofacial Surgery, University of Regensburg; Ettl, T.
2011-04-01
Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simplemore » method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.« less
Gardell, Alison M.; Qin, Qin; Rice, Robert H.; Li, Johnathan; Kültz, Dietmar
2014-01-01
Fish cell cultures are becoming more widely used models for investigating molecular mechanisms of physiological response to environmental challenge. In this study, we derived two immortalized Mozambique tilapia (Oreochromis mossambicus) cell lines from brain (OmB) and lip epithelium (OmL), and compared them to a previously immortalized bulbus arteriosus (TmB) cell line. The OmB and OmL cell lines were generated without or with Rho-associated kinase (ROCK) inhibitor/3T3 feeder layer supplementation. Although both approaches were successful, ROCK inhibitor/feeder layer supplementation was found to offer the advantages of selecting for epithelial-like cell type and decreasing time to immortalization. After immortalization (≥ passage 5), we characterized the proteomes of the newly derived cell lines (OmB and OmL) using LCMS and identified several unique cell markers for each line. Subsequently, osmotolerance for each of the three cell lines following acute exposure to elevated sodium chloride was evaluated. The acute maximum osmotolerance of these tilapia cell lines (>700 mOsm/kg) was markedly higher than that of any other known vertebrate cell line, but was significantly higher in the epithelial-like OmL cell line. To validate the physiological relevance of these tilapia cell lines, we quantified the effects of acute hyperosmotic challenge (450 mOsm/kg and 700 mOsm/kg) on the transcriptional regulation of two enzymes involved in biosynthesis of the compatible organic osmolyte, myo-inositol. Both enzymes were found to be robustly upregulated in all three tilapia cell lines. Therefore, the newly established tilapia cells lines represent valuable tools for studying molecular mechanisms involved in the osmotic stress response of euryhaline fish. PMID:24797371
HIV integration sites in latently infected cell lines: evidence of ongoing replication.
Symons, Jori; Chopra, Abha; Malatinkova, Eva; De Spiegelaere, Ward; Leary, Shay; Cooper, Don; Abana, Chike O; Rhodes, Ajantha; Rezaei, Simin D; Vandekerckhove, Linos; Mallal, Simon; Lewin, Sharon R; Cameron, Paul U
2017-01-13
Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines. Latently infected cell lines infected with intact virus demonstrated multiple distinct HIV integration sites (28 different sites in U1, 110 in ACH-2 and 117 in J1.1 per 150,000 cells). In contrast, cell lines infected with replication-incompetent viruses (J-Lat cells) demonstrated single integration sites. Following in vitro passaging of the ACH-2 cell line, we observed a significant increase in the frequency of unique HIV integration sites and there were multiple mutations and large deletions in the proviral DNA. When the ACH-2 cell line was cultured with the integrase inhibitor raltegravir, there was a significant decrease in the number of unique HIV integration sites and a transient increase in the frequency of 2-LTR circles consistent with virus replication in these cells. Cell lines latently infected with intact HIV demonstrated multiple unique HIV integration sites indicating that these cell lines are not clonal and in the ACH-2 cell line there was evidence of low level virus replication. These findings have implications for the use of latently infected cell lines as models of HIV latency and for the use of these cells as standards.
Taxonomy for Education and Training in Clinical Neuropsychology: past, present, and future.
Sperling, Scott A; Cimino, Cynthia R; Stricker, Nikki H; Heffelfinger, Amy K; Gess, Jennifer L; Osborn, Katie E; Roper, Brad L
2017-07-01
Historically, the clinical neuropsychology training community has not clearly or consistently defined education or training opportunities. The lack of consistency has limited students' and trainees' ability to accurately assess and compare the intensity of neuropsychology-specific training provided by programs. To address these issues and produce greater 'truth in advertising' across programs, CNS, with SCN's Education Advisory Committee (EAC), ADECN, AITCN, and APPCN constructed a specialty-specific taxonomy, namely, the Taxonomy for Education and Training in Clinical Neuropsychology. The taxonomy provides consensus in the description of training offered by doctoral, internship, and postdoctoral programs, as well as at the post-licensure stage. Although the CNS approved the taxonomy in February 2015, many programs have not adopted its language. Increased awareness of the taxonomy and the reasons behind its development and structure, as well as its potential benefits, are warranted. In 2016, a working group of clinical neuropsychologists from the EAC and APPCN, all authors of this manuscript, was created and tasked with disseminating information about the taxonomy. Group members held regular conference calls, leading to the generation of this manuscript. This manuscript is the primary byproduct of the working group. Its purpose is to (1) outline the history behind the development of the taxonomy, (2) detail its structure and utility, (3) address the expected impact of its adoption, and (4) call for its adoption across training programs. This manuscript outlines the development and structure of the clinical neuropsychology taxonomy and addresses the need for its adoption across training programs.
Vencloviene, Jone; Babarskiene, Ruta M; Dobozinskas, Paulius; Sakalyte, Gintare; Lopatiene, Kristina; Mikelionis, Nerijus
2015-02-27
We hypothesized that weather and space weather conditions were associated with the exacerbation of essential hypertension. The study was conducted during 2009-2010 in the city of Kaunas, Lithuania. We analyzed 13,475 cards from emergency ambulance calls (EACs), in which the conditions for the emergency calls were made coded I.10-I.15. The Kaunas Weather Station provided daily records of air temperature (T), wind speed (WS), relative humidity, and barometric pressure (BP). We evaluated the associations between daily weather variables and daily number of EACs by applying a multivariate Poisson regression. Unfavorable heliophysical conditions (two days after the active-stormy geomagnetic field or the days with solar WS>600 km/s) increased the daily number of elevated arterial blood pressure (EABP) by 12% (RR=1.12; 95% confidence interval (CI) 1.04-1.21); and WS≥3.5 knots during days of T<1.5 °C and T≥12.5 °C by 8% (RR=1.08; CI 1.04-1.12). An increase of T by 10 °C and an elevation of BP two days after by 10 hPa were associated with a decrease in RR by 3%. An additional effect of T was detected during days of T≥17.5 °C only in females. Women and patients with grade III arterial hypertension at the time of the ambulance call were more sensitive to weather conditions. These results may help in the understanding of the population's sensitivity to different weather conditions.
Why Cannot We have an Etiological Classification for the Patients with Granular Myringitis?
Bansal, Mohan
2017-09-01
Though granular myringitis (GM) is not a very rare disease it does not have any classification. Its exact etiology is not known. The granulations on tympanic membrane also occur in association with other lesions of external auditory canal (EAC) and middle ear. The aims of this study were to know the etiological factors of GM and classify the disease according to its etiological factors and associated disorders of EAC and middle ear. Data were retrieved from the search of four electronic databases: PubMed, EMBASE, Cochrane Library, and Google scholar. Relevant articles were also sought by a hand search review of reference books. The databases were searched using the key words otitis externa, external otitis, granular myringitis, granular otitis externa and myringitis. Data were extracted using a pre-defined data-extraction form. The following data were recorded (1) etiological and predisposing conditions; (2) pathological features; (3) associated disorders of external and middle ear. The study proposes the etiological classification of GM. It suggests two major groups: primary and secondary. The primary GM is basically idiopathic and these patients do no have evidences of any other types of otitis media and otitis externa. In the secondary GM the cause is obvious and the patients usually have associated otitis media and/or lesions of external ear canal. Author speculates that habit of self ear cleaning/scratching is a specific etiological factor in cases of primary GM but more studies are required to confirm this theory.
Vercruysse, Jean-Philippe; van Dinther, Joost J S; De Foer, Bert; Casselman, Jan; Somers, Thomas; Zarowski, Andrzej; Cremers, Cor C; Offeciers, Erwin
2016-07-01
To present the long-term surgical outcome of the bony mastoid and epitympanic obliteration technique with canal wall reconstruction (CWR-BOT) in adults with an unstable cavity after previous canal wall-down surgery for extensive cholesteatoma. Retrospective study. Therapeutic. Tertiary referral center. Fifty consecutive adult patients undergoing a CWR-BOT between 1998 and 2009. (A) Recurrence and residual rates of cholesteatoma, (B) postoperative hygienic status of the ear, including postoperative aspect of the tympanic membrane and external ear canal integrity (EAC), (C) functional outcome, and (D) long-term safety issues. (A) The percentage of ears remaining safe without recurrent or residual disease after CWR-BOT was 96% after a mean follow-up time of 101.8 months. Recurrent cholesteatoma occurred in 2% (n = 1) and a residual cholesteatoma was detected in 2% (n = 1) of the patients. (B) A safe dry, and trouble-free graft and selfcleaning EAC was achieved in 94%. (C) The postoperative hearing results showed a gain of 1.7 dB on pure-tone average air-conduction. (D) Nonecho planar diffusion-weighted imaging (non-EP DW magnetic resonance imaging) documented the residual (n = 1) and recurrent cholesteatoma (n = 1). The 1- and 5-year imaging follow-up revealed no other recurrent or residual disease. The CWR-BOT is a safe and very effective option for treatment of problematic unstable canal wall-down mastoid cavities, resulting in dry trouble-free ears.
Corral-Vázquez, C; Aguilar-Quesada, R; Catalina, P; Lucena-Aguilar, G; Ligero, G; Miranda, B; Carrillo-Ávila, J A
2017-06-01
Establishment of continuous cell lines from human normal and tumor tissues is an extended and useful methodology for molecular characterization of cancer pathophysiology and drug development in research laboratories. The exchange of these cell lines between different labs is a common practice that can compromise assays reliability due to contamination with microorganism such as mycoplasma or cells from different flasks that compromise experiment reproducibility and reliability. Great proportions of cell lines are contaminated with mycoplasma and/or are replaced by cells derived for a different origin during processing or distribution process. The scientific community has underestimated this problem and thousand of research experiment has been done with cell lines that are incorrectly identified and wrong scientific conclusions have been published. Regular contamination and authentication tests are necessary in order to avoid negative consequences of widespread misidentified and contaminated cell lines. Cell banks generate, store and distribute cell lines for research, being mandatory a consistent and continuous quality program. Methods implementation for guaranteeing both, the absence of mycoplasma and authentication in the supplied cell lines, has been performed in the Andalusian Health System Biobank. Specifically, precise results were obtained using real time PCR detection for mycoplasma and 10 STRs identification by capillary electrophoresis for cell line authentication. Advantages and disadvantages of these protocols are discussed.
Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis).
Jager, Martine J; Magner, J Antonio Bermudez; Ksander, Bruce R; Dubovy, Sander R
2016-08-01
To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines.
Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis)
Jager, Martine J.; Magner, J. Antonio Bermudez; Ksander, Bruce R.; Dubovy, Sander R.
2016-01-01
Purpose To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Methods Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Results Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. Conclusions All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines. PMID:28018010
Different toxic effects of YTX in tumor K-562 and lymphoblastoid cell lines
Fernández-Araujo, Andrea; Sánchez, Jon A.; Alfonso, Amparo; Vieytes, Mercedes R.; Botana, Luis M.
2015-01-01
Yessotoxin (YTX) modulates cellular phosphodiesterases (PDEs). In this regard, opposite effects had been described in the tumor model K-562 cell line and fresh human lymphocytes in terms of cell viability, cyclic adenosine 3',5'-cyclic monophosphate (cAMP) production and protein expression after YTX treatment. Studies in depth of the pathways activated by YTX in K-562 cell line, have demonstrated the activation of two different cell death types, apoptosis, and autophagy after 24 and 48 h of treatment, respectively. Furthermore, the key role of type 4A PDE (PDE4A) in both pathways activated by YTX was demonstrated. Therefore, taking into account the differences between cellular lines and fresh cells, a study of cell death pathways activated by YTX in a non-tumor cell line with mitotic activity, was performed. The cellular model used was the lymphoblastoid cell line that represents a non-tumor model with normal apoptotic and mitotic machinery. In this context, cell viability and cell proliferation, expression of proteins involved in cell death activated by YTX and mitochondrial mass, were studied after the incubation with the toxin. Opposite to the tumor model, no cell death activation was observed in lymphoblastoid cell line in the presence of YTX. In this sense, variations in apoptosis hallmarks were not detected in the lymphoblastoid cell line after YTX incubation, whereas this type I of programmed cell death was observed in K-562 cells. On the other hand, autophagy cell death was triggered in this cellular line, while other autophagic process is suggested in lymphoblastoid cells. These YTX effects are related to PDE4A in both cellular lines. In addition, while cell death is triggered in K-562 cells after YTX treatment, in lymphoblastoid cells the toxin stops cellular proliferation. These results point to YTX as a specific toxic compound of tumor cells, since in the non-tumor lymphoblastoid cell line, no cell death hallmarks are observed. PMID:26136685
Lung Cancer Cell Lines as Tools for Biomedical Discovery and Research
Girard, Luc; Lockwood, William W.; Lam, Wan L.; Minna, John D.
2010-01-01
Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from small cell and non–small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel. PMID:20679594
von Erichsen, J; Hecht, W; Löhberg-Gruene, C; Reinacher, M
2012-07-01
The purpose of the study was to evaluate clonality and presence of numerical chromosomal and centrosomal aberrations in 5 established feline fibrosarcoma cell lines and in a fetal dermal fibroblast cell line as a control. The clonality of all cell lines was examined using limited-dilution cloning. The number of chromosomes was counted in metaphase spreads. The immunocytochemical analysis of centrosome numbers was performed by indirect immunofluorescence using a monoclonal antibody that targets γ-tubulin, a well-characterized component of centrosomes. Monoclonal cell populations could be established from all cell lines. In all feline fibrosarcoma cell lines, the number of chromosomes deviated abnormally from the normal feline chromosome number of 2n = 38, ranging from 19 to 155 chromosomes per cell. Centrosome hyperamplification was observed in all 5 feline fibrosarcoma cell lines with a proportion of cells (5.7 to 15.2%) having more than 2 centrosomes. In the control cell line, only 0.6% of the cells had more than 2 centrosomes. In conclusion, the examinations revealed that centrosome hyperamplification occurs in feline fibrosarcoma cell lines. The feline fibrosarcoma cell lines possessed 10 to 25 times as many cells with centrosome hyperamplification as the control cell line. These observations suggest an association of numerical centrosome aberrations with karyotype instability by increasing the frequency of chromosome missegregation. The results of this study may be helpful for further characterization of feline fibrosarcomas and may contribute to the knowledge of cytogenetic factors that may be important for the pathogenesis of feline fibrosarcomas.
Attempt to develop taste bud models in three-dimensional culture.
Nishiyama, Miyako; Yuki, Saori; Fukano, Chiharu; Sako, Hideyuki; Miyamoto, Takenori; Tomooka, Yasuhiro
2011-09-01
Taste buds are the end organs of taste located in the gustatory papillae, which occur on the surface of the oral cavity. The goal of the present study was to establish a culture model mimicking the lingual taste bud of the mouse. To this end, three cell lines were employed: taste bud-derived cell lines (TBD cell lines), a lingual epithelial cell-derived cell line (20A cell line), and a mesenchymal cell-derived cell line (TMD cell line). TBD cells embedded in collagen gel formed three-dimensional clusters, which had an internal cavity equipped with a tight junction-like structure, a microvilluslike structure, and a laminin-positive layer surrounding the cluster. The cells with this epitheliumlike morphology expressed marker proteins of taste cells: gustducin and NCAM. TBD cells formed a monolayer on collagen gel when they were co-cultured with TMD cells. TBD, 20A, and TMD cell lines were maintained in a triple cell co-culture, in which TBD cells were pre-seeded as aggregates or in suspension on the collagen gel containing TMD cells, and 20A cells were laid over the TBD cells. TBD cells in the triple cell co-culture expressed NCAM. This result suggests that co-cultured TBD cells exhibited a characteristic of Type III taste cells. The culture model would be useful to study morphogenesis and functions of the gustatory organ.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Blattmann, Claudia, E-mail: claudia.blattmann@med.uni-heidelberg.d; Oertel, Susanne; Ehemann, Volker
2010-09-01
Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines. Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry. Results: SAHA induced anmore » inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80). Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.« less
Generation of genome-modified Drosophila cell lines using SwAP.
Franz, Alexandra; Brunner, Erich; Basler, Konrad
2017-10-02
The ease of generating genetically modified animals and cell lines has been markedly increased by the recent development of the versatile CRISPR/Cas9 tool. However, while the isolation of isogenic cell populations is usually straightforward for mammalian cell lines, the generation of clonal Drosophila cell lines has remained a longstanding challenge, hampered by the difficulty of getting Drosophila cells to grow at low densities. Here, we describe a highly efficient workflow to generate clonal Cas9-engineered Drosophila cell lines using a combination of cell pools, limiting dilution in conditioned medium and PCR with allele-specific primers, enabling the efficient selection of a clonal cell line with a suitable mutation profile. We validate the protocol by documenting the isolation, selection and verification of eight independently Cas9-edited armadillo mutant Drosophila cell lines. Our method provides a powerful and simple workflow that improves the utility of Drosophila cells for genetic studies with CRISPR/Cas9.
Santoso, D; Thornburg, R
2000-08-01
We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines.
Santoso, Djoko; Thornburg, Robert
2000-01-01
We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines. PMID:10938367
Yu, Sungryul; Kim, Taemook; Yoo, Kyung Hyun; Kang, Keunsoo
2017-05-06
Cell lines are often used as in vitro tools to mimic certain types of in vivo system; several cell lines, including MCF-7 and T47D, have been widely used in breast cancer studies without investigating the cell lines' characteristics. In this study, we compared the genome-wide binding profiles of ERα, PR, and P300, and the gene expression changes between MCF-7 and T47D cell lines that represent the luminal A subtype of breast cancer. Surprisingly, several thousand genes were differentially expressed under estrogenic condition. In addition, ERα, PR, and P300 binding to regulatory elements showed distinct genomic landscapes between MCF-7 and T47D cell lines in the same hormonal states. In particular, the T47D cell line was markedly susceptible to progesterone, whereas the MCF-7 cell line did not respond to progesterone in the presence of estrogen. Consistently, changes in the expression level of the PR-target gene, STAT5A, were only observed in the T47D cell line, not the MCF-7 cell line, when treated with progesterone. Overall, the results highlight the importance of selecting appropriate cell lines for breast cancer studies and suggest that T47D cell lines can be an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.
Kniss, Douglas A; Summerfield, Taryn L
2014-08-01
Continuous cell lines are used frequently in reproductive biology research to study problems in early pregnancy events and parturition. It has been recognized for 50 years that many mammalian cell lines contain inter- or intraspecies contaminations with other cells. However, most investigators do not routinely test their culture systems for cross-contamination. The most frequent contributor to cross-contamination of cell lines is the HeLa cell isolated from an aggressive cervical adenocarcinoma. We report on the discovery of HeLa cell contamination of the human endometrial epithelial cell line HES isolated in our laboratory. Short tandem repeat analysis of 9 unique genetic loci demonstrated molecular identity between HES and HeLa cells. In addition, we verified that WISH cells, isolated originally from human amnion epithelium, were also contaminated with HeLa cells. Inasmuch as our laboratory did not culture HeLa cells at the time of HES cell derivations, the source of contamination was the WISH cell line. These data highlight the need for continued diligence in authenticating cell lines used in reproductive biology research. © The Author(s) 2014.
2011-01-01
Background Fatty acid binding proteins (FABP) play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. Methods Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. Results General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. Conclusions Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the same cancer. The FABP patterns in the cell lines do not always reflect the real situation in the tumours. These facts have to be considered in functional studies concerning the different FABPs. PMID:21767383
Madhusudana, Shampur Narayan; Sundaramoorthy, Subha; Ullas, Padinjaremattatthil Thankappan
2010-12-01
A confirmatory rabies diagnosis can be achieved by rapid virus isolation in cell culture using brain tissue from the suspect animal. Several cell lines have been used for this purpose and the murine neuroblastoma cell line Neuro-2a has been found to be the most sensitive. The human embryonic kidney cell line HEK-293 is known to express several neuronal proteins and is believed to be of neuronal origin. We hypothesized that this cell line could be susceptible to rabies virus, which is highly neurotropic. First we tested the sensitivity of HEK-293 cells to the laboratory strain, challenge virus standard (CVS). We then tested 120 brain samples from different animals and humans suspected to have died of rabies by fluorescent antibody test (FAT). Both FAT-positive and FAT-negative brains were tested for virus isolation using Neuro-2a, BHK-21, and HEK-293 cell lines and also by mouse inoculation. There was 100% correlation between FAT, virus isolation in Neuro-2a and HEK-293 cells, and mouse inoculation. However, the rate of virus isolation in the BHK-21 cell line was only 28% when compared to the other cell lines. The sensitivity of HEK-293 to CVS strain of virus was similar to that of Neuro-2a. We conclude that the HEK-293 cell line is as sensitive as the Neuro-2a cell line for the rapid isolation of rabies virus and may serve as an alternative cell line for rabies diagnosis and future research. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Liu, Jun; Luo, Yan; Zheng, Liming; Liu, Qingqing; Yang, Zhongcai; Wang, Yongsheng; Su, Jianmin; Quan, Fusheng; Zhang, Yong
2013-10-01
This study was performed to qualify goat fetal fibroblast (GFF) cell lines for genetic modification and somatic cell nuclear transfer (SCNT) to produce human lysozyme (hLYZ) transgenic goats. Nine GFF cell lines were established from different fetuses, and the proliferative lifespan and chromosomal stability were analyzed. The results suggested that cell lines with a longer lifespan had stable chromosomes compared with those of cells lines with a shorter lifespan. According to the proliferative lifespan, we divided GFF cell lines into two groups: cell lines with a long lifespan (GFF1/2/7/8/9; group L) and cell lines with a short lifespan (GFF3/4/5/6; group S). Next, a hLYZ expression vector was introduced into these cell lines by electroporation. The efficiencies of colony formation, expansion in culture, and the quality of transgenic clonal cell lines were significant higher in group L than those in group S. The mean fusion rate and blastocyst rate in group L were higher than those in group S (80.3 ± 1.7 vs. 65.1 ± 4.2 % and 19.5 ± 0.6 vs. 15.1 ± 1.1 %, respectively, P < 0.05). After transferring cloned embryos into the oviducts of recipient goats, three live kids were born. PCR and Southern blot analyses confirmed integration of the transgene in cloned goats. In conclusion, the lifespan of GFF cell lines has a major effect on the efficiency to produce transgenic cloned goats. Therefore, the proliferative lifespan of primary cells may be used as a criterion to characterize the quality of cell lines for genetic modification and SCNT.
[Establishment of Z-HL16C cell line.].
Chen, J P; Li, J; Zhao, S L; Tian, J Y; Ye, F
2006-09-01
To establish and study the nature and the application of Z-HL16C cell line. The cell line was continuously passed, frozen stored and recovered. Its application was expanded and the cell type was identified. The cell line had an epithelial-cell-like shape, the size appeared uniform, the cell boundary was distinct. It has been continuously passed, frozen stored and recovered for ten years. Its recovery rate was about 90%. It has been proved to be sensitive to the tested viruses which were enteroviruses (Polio, Cox, Echo), influenza viruses, parainfluenzaviruses, adenoviruses, measles virus. This cell line has been identified as a cancerization cell. The cell line Z-HL16C has been stably established, it has a broad spectrum in sensitivity for culturing viruses.
Development and characterization of a cell line WAF from freshwater shark Wallago attu.
Dubey, Akhilesh; Goswami, Mukunda; Yadav, Kamalendra; Sharma, Bhagwati S
2014-02-01
A new epithelial cell line, WAF was developed from caudal fin of freshwater shark, Wallago attu. The cell line was optimally maintained at 28 °C in Leibovitz-15 (L-15) medium supplemented with 20 % fetal bovine serum. The cell line was characterized by various cytogenetic and molecular markers. The cytogenetic analysis revealed a diploid count of 86 chromosomes at different passages. The origin of the cell lines was confirmed by the amplification of 547 and 654 bp sequences of 16S rRNA and cytochrome oxidase subunit I genes of mitochondrial DNA, respectively. WAF cells were characterized for their growth characteristics at different temperature and serum concentration. Epithelial morphology of the cell line was confirmed using immunocytochemistry. Further cell plating efficiency, transfection efficiency and viability of cryopreserved WAF cells was also determined. Cytotoxicity and genotoxicity assessment of cadmium salts on WAF cells by MTT, NR and comet assay illustrated the utility of this cell line as an in vitro model for aquatic toxicological studies. The cell line will be further useful for studying oxidative stress markers against aquatic pollutants.
Characterization of a Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cell Line CVG-1.
Velásquez, Celestino; Amako, Yutaka; Harold, Alexis; Toptan, Tuna; Chang, Yuan; Shuda, Masahiro
2018-01-01
Merkel cell polyomavirus (MCV) plays a causal role in ∼80% of Merkel cell carcinomas (MCC). MCV is clonally integrated into the MCC tumor genome, which results in persistent expression of large T (LT) and small T (sT) antigen oncoproteins encoded by the early locus. In MCV-positive MCC tumors, LT is truncated by premature stop codons or deletions that lead to loss of the C-terminal origin binding (OBD) and helicase domains important for replication. The N-terminal Rb binding domain remains intact. MCV-positive cell lines derived from MCC explants have been valuable tools to study the molecular mechanism of MCV-induced Merkel cell carcinogenesis. Although all cell lines have integrated MCV and express truncated LT antigens, the molecular sizes of the LT proteins differ between cell lines. The copy number of integrated viral genome also varies across cell lines, leading to significantly different levels of viral protein expression. Nevertheless, these cell lines share phenotypic similarities in cell morphology, growth characteristics, and neuroendocrine marker expression. Several low-passage MCV-positive MCC cell lines have been established since the identification of MCV. We describe a new MCV-positive MCV cell line, CVG-1, with features distinct from previously reported cell lines. CVG-1 tumor cells grow in more discohesive clusters in loose round cell suspension, and individual cells show dramatic size heterogeneity. It is the first cell line to encode an MCV sT polymorphism resulting in a unique leucine (L) to proline (P) substitution mutation at amino acid 144. CVG-1 possesses a LT truncation pattern near identical to that of MKL-1 cells differing by the last two C-terminal amino acids and also shows an LT protein expression level similar to MKL-1. Viral T antigen knockdown reveals that, like other MCV-positive MCC cell lines, CVG-1 requires T antigen expression for cell proliferation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Williams, K.; Chubb, C.; Huberman, E.
High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteinsmore » were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.« less
Derivation and characterization of a pig embryonic stem cell-derived exocrine pancreatic cell line
USDA-ARS?s Scientific Manuscript database
The establishment and initial characterization of a pig embryonic stem cell-derived pancreatic cell line, PICM-31, and a colony-cloned derivative cell line, PICM-31A, is described. The cell lines were propagated for several months at split ratios of 1:3 or 1:5 at each passage on STO feeder cells af...
ASADA, Hajime; TOMIYASU, Hirotaka; GOTO-KOSHINO, Yuko; FUJINO, Yasuhito; OHNO, Koichi; TSUJIMOTO, Hajime
2015-01-01
Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS. PMID:25715778
Asada, Hajime; Tomiyasu, Hirotaka; Goto-Koshino, Yuko; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime
2015-06-01
Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS.
Phuchareon, Janyaporn; Ohta, Yoshihito; Woo, Jonathan M.; Eisele, David W.; Tetsu, Osamu
2009-01-01
Adenoid cystic carcinoma (ACC) is the second most common malignant neoplasm of the salivary glands. Most patients survive more than 5 years after surgery and postoperative radiation therapy. The 10 year survival rate, however, drops to 40%, due to locoregional recurrences and distant metastases. Improving long-term survival in ACC requires the development of more effective systemic therapies based on a better understanding of the biologic behavior of ACC. Much preclinical research in this field involves the use of cultured cells and, to date, several ACC cell lines have been established. Authentication of these cell lines, however, has not been reported. We performed DNA fingerprint analysis on six ACC cell lines using short tandem repeat (STR) examinations and found that all six cell lines had been contaminated with other cells. ACC2, ACC3, and ACCM were determined to be cervical cancer cells (HeLa cells), whereas the ACCS cell line was composed of T24 urinary bladder cancer cells. ACCNS and CAC2 cells were contaminated with cells derived from non-human mammalian species: the cells labeled ACCNS were mouse cells and the CAC2 cells were rat cells. These observations suggest that future studies using ACC cell lines should include cell line authentication to avoid the use of contaminated or non-human cells. PMID:19557180
Continuous human cell lines and method of making same
Stampfer, Martha R.
1989-01-01
Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo[a]pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors.
Zhu, Bing; Guo, Zhili; Jin, Muzi; Bai, Yujuan; Yang, Wenliang; Hui, Lihua
2018-05-01
To establish a dermal sheath cell line, a dermal papilla cell line and a outer root sheath cell line from Cashmere goat and clarify the similarities and differences among them. We established a dermal sheath cell line, a dermal papilla cell line and a outer root sheath cell line from the pelage skin hair follicles of Cashmere goat. The growth rate of dermal sheath cells was intermediate between that of dermal papilla cells and outer root sheath cells. Immunofluorescence experiments and reverse transcription-polymerase chain reaction analysis showed that at both the transcriptional and translational levels, the dermal sheath cells were alpha-smooth muscle actin (α-SMA) + /cytokeratin 13 + , while the dermal papilla cells were α-SMA + /cytokeratin 13 - and the outer root sheath cells were α-SMA - /cytokeratin 13 + . Patterns of cytokeratin 13 expression could distinguish the dermal sheath cells from the dermal papilla cells. These results suggest that cytokeratin 13 could serve as a novel biomarker for dermal sheath cells of Cashmere goat, and should prove useful for researchers investigating dermal stem cells or interaction of different types of cells during hair cycle.
Lapointe, Jason F; Dunphy, Gary B; Giannoulis, Paschalis; Mandato, Craig A; Nardi, James B; Gharib, Osama H; Niven, Donald F
2011-11-01
The innate non-self response systems of the deciduous tree pest, the forest tent caterpillar, Malacosoma disstria has been documented by us in terms of in vitro and in vivo reactions towards the Gram-positive nonpathogenic bacterium, Bacillus subtilis and Gram-negative pathogenic microbe, Xenorhabdus nematophila and their respective surface antigens, lipopoteichoic acids (LTA) and lipopolysaccharides (LPS). These studies, often conducted in whole and diluted hemolymph, preclude examination of plasma-free cellular (hemocyte) responses. Plasma-free hemocytes as primary cultures are difficult to obtain. The floating cell line Md66 and attached cell line Md108 from M. disstria hemocytes were examined as a model for plasma-free M. disstria hemocyte non-self responses. Herein, it was established that although both lines differed from each other and from the primary hemocyte cultures of M. disstria in growth parameters, cell composition and sizes both cell lines displayed granular cell-like (GL) cells and plasmatocyte-like (PL) cells according to morphological criteria and to some extent antigenic similarities based on labeling with anti-Chrysodeixis includens hemocyte monoclonal antibodies. Hemocyte-specific neuroglian-like protein was detected on cells of both cell lines and in the primary hemocyte cultures albeit with staining patterns differing according to culture and cell types, confluency levels and cell-cell adhesion. Both cell lines bound B. subtilis and X. nematophila, the reaction extent varying with the cell line and its cell types. LPS damaged both cell types in the two cell lines whereas LTA enhanced the adhesion of Md66 GL cells to flask surfaces followed by PL cell adhesion. PL cells of both lines, like the primary cultures, phagocytosed FITC-labeled B. subtilis; only Md108 GL cells phagocytosed B. subtilis. In either case phagocytosis was always less in frequency and intensity than the primary cultures. Proteins released from the cell lines differed in pattern and magnitude but contained bacterial binding proteins that enhanced differential bacterial adhesion to both cell types in both cell lines: the GL cells both cultures, and those of granular cells in primary cultures, were more involved than the primary plasmatocytes and PL cells. Only Md66 cells possessed lysozyme and both cell types of both lines contained phenoloxidase. Neither enzyme type was released during early phase reaction with the bacteria. LPS inhibited phenoloxidase activity. The similarities and differences between the lines and primary cultures make Md66 and Md108 useful for the systematic examination of plasma-free cellular non-self reactions. Copyright © 2011 Elsevier Inc. All rights reserved.
2010-01-01
Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity. PMID:20406486
Molecular characterization of breast cancer cell lines through multiple omic approaches.
Smith, Shari E; Mellor, Paul; Ward, Alison K; Kendall, Stephanie; McDonald, Megan; Vizeacoumar, Frederick S; Vizeacoumar, Franco J; Napper, Scott; Anderson, Deborah H
2017-06-05
Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources. In addition, new information about cellular pathways that are activated within each cell line was generated. We determined key protein expression data using immunoblot analyses. In addition, two analyses on serum-starved cells were carried out to identify cellular proteins and pathways that are activated in these cells. These analyses were performed using a commercial PathScan array and a novel and more extensive phosphopeptide-based kinome analysis that queries 1290 phosphorylation events in major signaling pathways. Data about this panel of breast cancer cell lines was also accessed from several online sources, compiled and summarized for the following areas: molecular classification, mRNA expression, mutational status of key proteins and other possible cancer-associated mutations, and the tumorigenic and metastatic capacity in mouse xenograft models of breast cancer. The cell lines that were characterized included 10 estrogen receptor (ER)-positive, 12 human epidermal growth factor receptor 2 (HER2)-amplified and 18 triple negative breast cancer cell lines, in addition to 4 non-tumorigenic breast cell lines. Within each subtype, there was significant genetic heterogeneity that could impact both the selection of model cell lines and the interpretation of the results obtained. To capture the net activation of key signaling pathways as a result of these mutational combinations, profiled pathway activation status was examined. This provided further clarity for which cell lines were particularly deregulated in common or unique ways. These two new kinase or "Kin-OMIC" analyses add another dimension of important data about these frequently used breast cancer cell lines. This will assist researchers in selecting the most appropriate cell lines to use for breast cancer studies and provide context for the interpretation of the emerging results.
Development and characterization of two cell lines PDF and PDH from Puntius denisonii (Day 1865).
Lakra, Wazir S; Goswami, M; Yadav, Kamalendra; Gopalakrishnan, A; Patiyal, R S; Singh, M
2011-02-01
The Puntius denisonii colloquially and more popularly referred to as Miss Kerala is a subtropical fish belonging to the genus Puntius (Barb) and family Cyprinidae. Two cell lines PDF and PDH were developed from the caudal fin and heart of P. denisonii, respectively. The cell lines were optimally maintained at 26°C in Leibovitz-15 medium supplemented with 10% fetal bovine serum. A diploid count of 50 chromosomes at passage 50 was observed in both the cell lines. The high growth potential of the cell lines was reflected from the cell doubling time of 28 and 30 h of PDF and PDH cell lines, respectively. The viability of the PDF and PDH cell lines was 70% and 76%, respectively, after 4 mo of storage in liquid nitrogen (-196°C). The origin of the cell lines was confirmed by the amplification of 653 bp fragments of cytochrome oxidase subunit I of mitochondrial DNA genes.
1982-02-01
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