Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma

PubMed Central

Marote, Georgina; Abramo, Francesca; McKay, Jenny; Thomson, Calum; Beltran, Mariana; Millar, Michael; Priestnall, Simon; Dobson, Jane; Costantino-Casas, Fernando; Petrou, Terry; McGonnell, Imelda M.; Davies, Anthony J.; Weetman, Malcolm; Garden, Oliver A.; Masters, John R.; Thrasivoulou, Christopher; Ahmed, Aamir

2016-01-01

Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease. PMID:27559731

[Establishment of the retrovirus-mediated murine model with MLL-AF9 leukemia].

PubMed

Xu, Si-Miao; Yang, Yang; Zhou, Mi; Zhao, Xue-Jiao; Qin, Yu; Zhang, Pei-Ling; Yuan, Rui-Feng; Zhou, Jian-Feng; Fang, Yong

2013-10-01

This study was purposed to establish a retrovirus-mediated murine model with MLL-AF9 leukemia, so as to provide a basis for further investigation of the pathogenesis and therapeutic strategy of MLL associated leukemia. Murine (CD45.2) primary hematopoietic precursor positively selected for expression of the progenitor marker c-Kit by means of MACS were transduced with a retrovirus carrying MLL-AF9 fusion gene. After cultured in vitro, the transduced cells were injected intravenously through the tail vein into the lethally irradiated mice (CD45.1). PCR, flow cytometry and morphological observation were employed to evaluate the murine leukemia model system. The results showed that MLL-AF9 fusion gene was expressed in the infected cells, and the cells had a dramatically enhanced potential to generate myeloid colonies with primitive and immature morphology. Flow cytometric analysis revealed that the immortalized cells highly expressed myeloid lineage surface markers Gr-1 and Mac-1. Moreover, the expression levels of Hoxa9 and Meis1 mRNA were significantly higher in the MLL-AF9 cells than that in control. The mice transplanted with MLL-AF9 cells displayed typical signs of leukemia within 6-12 weeks. Extensive infiltration leukemic cells was observed in the Wright-Giemsa stained peripheral blood smear and bone marrow, and also in the histology of liver and spleen. Flow cytometric analysis of the bone marrow and spleen cells demonstrated that the CD45.2 populations expressed highly myeloid markers Gr-1 and Mac-1. The leukemic mice died within 12 weeks. It is concluded that the retrovirus-mediated murine model with MLL-AF9 leukemia is successfully established, which can be applied in the subsequent researches.

The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.

PubMed

Whisenant, Thomas C; Peralta, Eigen R; Aarreberg, Lauren D; Gao, Nina J; Head, Steven R; Ordoukhanian, Phillip; Williamson, Jamie R; Salomon, Daniel R

2015-01-01

Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as "central" interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, "peripheral" interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation.

The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells

PubMed Central

Aarreberg, Lauren D.; Gao, Nina J.; Head, Steven R.; Ordoukhanian, Phillip; Williamson, Jamie R.; Salomon, Daniel R.

2015-01-01

Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as “central” interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, “peripheral” interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation. PMID:26641092

Nanotechnology Aerospace Applications (Applications aerospatiales de la nanotechnologie) (CD-ROM)

DTIC Science & Technology

ABSTRACT: The Educational Notes contain the abstracts and the lecture material of ten presentations, which provide a general introduction into... commercialisation . The lectures were held in October and November 2006 in four cities, namely Seattle, USA, Montreal, CAN, Ljubljana, SVN, and Bordeaux, FRA. The

Atrial Electromechanical Properties in Coeliac Disease.

PubMed

Efe, Tolga Han; Ertem, Ahmet Goktug; Coskun, Yusuf; Bilgin, Murat; Algul, Engin; Beton, Osman; Asarcikli, Lale Dinc; Erat, Mehmet; Ayturk, Mehmet; Yuksel, Ilhami; Yeter, Ekrem

2016-02-01

Coeliac disease (CD) is an autoimmune and inflammatory disorder of the small intestine. There is reasonable evidence linking inflammation to the initiation and continuation of atrial fibrillation (AF) in inflammatory conditions. Atrial electro-mechanic delay (EMD) was suggested as an early marker of AF in previous studies. The objectives of this study were to evaluate atrial electromechanical properties measured by tissue Doppler imaging and simultaneous electrocardiography (ECG) tracing in patients with CD. Thirty-nine patients with coeliac disease (CD), and 26 healthy volunteers, matched for age and sex, were enrolled in the study. Atrial electromechanical properties were measured by using transthoracic echocardiography and surface ECG. Interatrial electro-mechanic delay (EMD), left intraatrial EMD, right intratrial EMD were calculated. There was no difference between CD patients and healthy volunteers in terms of basal characteristics. Patients with CD had significantly prolonged left and right intraatrial EMDs, and interatrial EMD compared to healthy controls (p= 0.03, p= 0.02, p<0.0001, respectively). Interatrial EMD was positively correlated with age, disease duration, anti-gliadin IgG, anti-endomysium and disease status. In multiple linear regression, interatrial EMD was independently associated with disease duration, anti-endomysium and disease status after adjusting for age and sex. In the present study, atrial EMDs were found significantly higher in patients with CD compared with healthy individuals. Measurement of atrial EMD parameters might be used to predict the risk of development of AF in patients with CD. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Does fluorescence diagnosis have a role in follow up of response to therapy in mycosis fungoides?

PubMed

Bosseila, Manal; Mahgoub, Doaa; El-Sayed, Abeer; Salama, Dina; Abd El-Moneim, Marwa; Al-Helf, Fatma

2014-12-01

Monitoring of tumor burden during mycosis fungoides (MF) treatment, is crucial to adjust therapy accordingly. This is usually achieved through combined by clinical assessment with histopathological and immunohistochemical evaluation. To assess the validity of fluorescence diagnosis (FD) in the measurement of response to therapy in early MF, using in comparison flow cytometric technique of skin biopsies for CD4+/CD7- malignant T-cell count before and after therapy. Twenty-two patients of histologically proven early MF (stages Ia, Ib, IIa) were subjected to fluorescence diagnosis of their most affected skin lesion before and after 12 weeks of phototherapy with or without combination therapy. In comparison flow cytometric assessment of skin biopsies for CD4+/CD7- malignant T-cell count was evaluated before and after therapy from skin biopsy of the same lesion. All tested MF lesions showed varying degrees of fluorescence by FD at week zero, with a mean accumulation factor (AF), which is the fluorescence ratio between the tumor tissue and normal skin, of 2.2. After 12 weeks of therapy, the mean AF showed significant reduction to 1.94 (p=0.009). The percent of CD4+/CD7- cells dropped significantly after treatment (p=0.029). No correlation between CD4+/CD7- cell counts and the mean AF could be deduced. In cases of mycosis fungoides, fluorescence diagnosis can represent an effective tool for evaluating the response to therapy. Changes in accumulation factor values can be used for follow-up of therapy in the same patient, but it should not be used as an absolute value. Copyright © 2014 Elsevier B.V. All rights reserved.

Role of Two Cell Wall Amidases in Septal Junction and Nanopore Formation in the Multicellular Cyanobacterium Anabaena sp. PCC 7120

PubMed Central

Bornikoel, Jan; Carrión, Alejandro; Fan, Qing; Flores, Enrique; Forchhammer, Karl; Mariscal, Vicente; Mullineaux, Conrad W.; Perez, Rebeca; Silber, Nadine; Wolk, C. Peter; Maldener, Iris

2017-01-01

Filamentous cyanobacteria have developed a strategy to perform incompatible processes in one filament by differentiating specialized cell types, N2-fixing heterocysts and CO2-fixing, photosynthetic, vegetative cells. These bacteria can be considered true multicellular organisms with cells exchanging metabolites and signaling molecules via septal junctions, involving the SepJ and FraCD proteins. Previously, it was shown that the cell wall lytic N-acetylmuramyl-L-alanine amidase, AmiC2, is essential for cell–cell communication in Nostoc punctiforme. This enzyme perforates the septal peptidoglycan creating an array of nanopores, which may be the framework for septal junction complexes. In Anabaena sp. PCC 7120, two homologs of AmiC2, encoded by amiC1 and amiC2, were identified and investigated in two different studies. Here, we compare the function of both AmiC proteins by characterizing different Anabaena amiC mutants, which was not possible in N. punctiforme, because there the amiC1 gene could not be inactivated. This study shows the different impact of each protein on nanopore array formation, the process of cell–cell communication, septal protein localization, and heterocyst differentiation. Inactivation of either amidase resulted in significant reduction in nanopore count and in the rate of fluorescent tracer exchange between neighboring cells measured by FRAP analysis. In an amiC1 amiC2 double mutant, filament morphology was affected and heterocyst differentiation was abolished. Furthermore, the inactivation of amiC1 influenced SepJ localization and prevented the filament-fragmentation phenotype that is characteristic of sepJ or fraC fraD mutants. Our findings suggest that both amidases are to some extent redundant in their function, and describe a functional relationship of AmiC1 and septal proteins SepJ and FraCD. PMID:28929086

Role of Two Cell Wall Amidases in Septal Junction and Nanopore Formation in the Multicellular Cyanobacterium Anabaena sp. PCC 7120.

PubMed

Bornikoel, Jan; Carrión, Alejandro; Fan, Qing; Flores, Enrique; Forchhammer, Karl; Mariscal, Vicente; Mullineaux, Conrad W; Perez, Rebeca; Silber, Nadine; Wolk, C Peter; Maldener, Iris

2017-01-01

Filamentous cyanobacteria have developed a strategy to perform incompatible processes in one filament by differentiating specialized cell types, N 2 -fixing heterocysts and CO 2 -fixing, photosynthetic, vegetative cells. These bacteria can be considered true multicellular organisms with cells exchanging metabolites and signaling molecules via septal junctions, involving the SepJ and FraCD proteins. Previously, it was shown that the cell wall lytic N -acetylmuramyl-L-alanine amidase, AmiC2, is essential for cell-cell communication in Nostoc punctiforme . This enzyme perforates the septal peptidoglycan creating an array of nanopores, which may be the framework for septal junction complexes. In Anabaena sp. PCC 7120, two homologs of AmiC2, encoded by amiC1 and amiC2 , were identified and investigated in two different studies. Here, we compare the function of both AmiC proteins by characterizing different Anabaena amiC mutants, which was not possible in N. punctiforme , because there the amiC1 gene could not be inactivated. This study shows the different impact of each protein on nanopore array formation, the process of cell-cell communication, septal protein localization, and heterocyst differentiation. Inactivation of either amidase resulted in significant reduction in nanopore count and in the rate of fluorescent tracer exchange between neighboring cells measured by FRAP analysis. In an amiC1 amiC2 double mutant, filament morphology was affected and heterocyst differentiation was abolished. Furthermore, the inactivation of amiC1 influenced SepJ localization and prevented the filament-fragmentation phenotype that is characteristic of sepJ or fraC fraD mutants. Our findings suggest that both amidases are to some extent redundant in their function, and describe a functional relationship of AmiC1 and septal proteins SepJ and FraCD.

A candidate anti-HIV reservoir compound, auranofin, exerts a selective ‘anti-memory' effect by exploiting the baseline oxidative status of lymphocytes

PubMed Central

Chirullo, B; Sgarbanti, R; Limongi, D; Shytaj, I L; Alvarez, D; Das, B; Boe, A; DaFonseca, S; Chomont, N; Liotta, L; III Petricoin, E; Norelli, S; Pelosi, E; Garaci, E; Savarino, A; Palamara, A T

2013-01-01

Central memory (TCM) and transitional memory (TTM) CD4+ T cells are known to be the major cellular reservoirs for HIV, as these cells can harbor a transcriptionally silent form of viral DNA that is not targeted by either the immune system or current antiretroviral drug regimens. In the present study, we explored the molecular bases of the anti-HIV reservoir effects of auranofin (AF), a pro-oxidant gold-based drug and a candidate compound for a cure of AIDS. We here show that TCM and TTM lymphocytes have lower baseline antioxidant defenses as compared with their naive counterpart. These differences are mirrored by the effects exerted by AF on T-lymphocytes: AF was able to exert a pro-differentiating and pro-apoptotic effect, which was more pronounced in the memory subsets. AF induced an early activation of the p38 mitogen-activated protein kinase (p38 MAPK) followed by mitochondrial depolarization and a final burst in intracellular peroxides. The pro-differentiating effect was characterized by a downregulation of the CD27 marker expression. Interestingly, AF-induced apoptosis was inhibited by pyruvate, a well-known peroxide scavenger, but pyruvate did not inhibit the pro-differentiating effect of AF, indicating that the pro-apoptotic and pro-differentiating effects involve different pathways. In conclusion, our results demonstrate that AF selectively targets the TCM/TTM lymphocyte subsets, which encompass the HIV reservoir, by affecting redox-sensitive cell death pathways. PMID:24309931

Gene expression of stem cells at different stages of ontological human development.

PubMed

Allegra, Adolfo; Altomare, Roberta; Curcio, Patrizia; Santoro, Alessandra; Lo Monte, Attilio I; Mazzola, Sergio; Marino, Angelo

2013-10-01

To compare multipotent mesenchymal stem cells (MSCs) obtained from chorionic villi (CV), amniotic fluid (AF) and placenta, with regard to their phenotype and gene expression, in order to understand if MSCs derived from different extra-embryonic tissues, at different stages of human ontological development, present distinct stemness characteristics. MSCs obtained from 30 samples of CV, 30 of AF and 10 placentas (obtained from elective caesarean sections) were compared. MSCs at second confluence cultures were characterized by immunophenotypic analysis with flow cytometry using FACS CANTO II. The expression of the genes Oct-4 (Octamer-binding transcription factor 4, also known as POU5F1), Sox-2 (SRY box-containing factor 2), Nanog, Rex-1 (Zfp-42) and Pax-6 (Paired Box Protein-6), was analyzed. Real-time quantitative PCR was performed by ABI Prism 7700, after RNA isolation and retro-transcription in cDNA. Statistical analysis was performed using non-parametric test Kruskal-Wallis (XLSTAT 2011) and confirmed by REST software, to estimate fold changes between samples. Each gene was defined differentially expressed if p-value was <0.05. Cells from all samples were negative for haematopoietic antigens CD45, CD34, CD117 and CD33 and positive for the typical MSCs antigens CD13, CD73 and CD90. Nevertheless, MSCs from AF and placentas showed different fluorescence intensity, reflecting the heterogeneity of these tissues. The gene expression of OCT-4, SOX-2, NANOG was not significantly different among the three groups. In AF, REX-1 and PAX-6 showed a higher expression in comparison to CV. MSCs of different extra-embryonic tissues showed no differences in immunophenotype when collected from second confluence cultures. The expression of OCT-4, NANOG and SOX-2 was not significantly different, demonstrating that all fetal sources are suitable for obtaining MSCs. These results open new possibilities for the clinical use of MSCs derived from easily accessible sources, in order to develop new protocols for clinical and experimental research. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The role of human chorionic gonadotropin in regulation of naïve and memory T cells activity in vitro.

PubMed

Zamorina, S A; Litvinova, L S; Yurova, K A; Khaziakhmatova, O G; Timganova, V P; Bochkova, M S; Khramtsov, P V; Rayev, M B

2018-01-01

The role of human chorionic gonadotropin (hCG) in the regulation of molecular genetics factors determining the functional activity of human naïve and memory T cells in vitro was studied. It was found that hCG (10 and 100IU/ml) inhibited CD28 and CD25 expression on the naïve T cells (CD45RA+) and CD25 expression on the memory T cells (CD45R0+). hCG didn't affect the CD71 proliferation marker expression in total. Nevertheless, hCG reduced the percentage of proliferating memory T cells with simultaneous suppression of CD71 expression on proliferating CD45R0+cells. In parallel, expression of U2af1l4, Gfi1, and hnRNPLL genes, which are Ptprc gene alternative splicing regulators was evaluated. It was established that hCG stimulated the expression of U2af1l4 and hnRNPLL genes, responsible for the assembly of CD45R0 in memory T cells, but reduced the expression of Gfi1 in these cells. In general, hCG promotes the differentiation of memory T cells by increasing of CD45R0 expression, but inhibits proliferation and CD25 expression which reflects their functional activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Amniotic-Fluid Stem Cells: Growth Dynamics and Differentiation Potential after a CD-117-Based Selection Procedure

PubMed Central

Arnhold, S.; Glüer, S.; Hartmann, K.; Raabe, O.; Addicks, K.; Wenisch, S.; Hoopmann, M.

2011-01-01

Amniotic fluid (AF) has become an interesting source of fetal stem cells. However, AF contains heterogeneous and multiple, partially differentiated cell types. After isolation from the amniotic fluid, cells were characterized regarding their morphology and growth dynamics. They were sorted by magnetic associated cell sorting using the surface marker CD 117. In order to show stem cell characteristics such as pluripotency and to evaluate a possible therapeutic application of these cells, AF fluid-derived stem cells were differentiated along the adipogenic, osteogenic, and chondrogenic as well as the neuronal lineage under hypoxic conditions. Our findings reveal that magnetic associated cell sorting (MACS) does not markedly influence growth characteristics as demonstrated by the generation doubling time. There was, however, an effect regarding an altered adipogenic, osteogenic, and chondrogenic differentiation capacity in the selected cell fraction. In contrast, in the unselected cell population neuronal differentiation is enhanced. PMID:21437196

AF Ni-Cd cell qualification program

NASA Technical Reports Server (NTRS)

Hall, Steve; Brown, Harry; Collins, G.; Hwang, Warren

1994-01-01

The present status of the USAF NiCd cell qualification program, which is underway at the Naval Surface Warfare Center-Crane Division, is summarized. The following topics are discussed: overview; background; purpose; stress tests; results for super Ni-Cd; results for SAFT cells; GPS stress test; GPS simulated orbit; and results for gates cells. The discussion is presented in viewgraph format.

Deacylation of Purified Lipopolysaccharides by Cellular and Extracellular Components of a Sterile Rabbit Peritoneal Inflammatory Exudate

PubMed Central

Weinrauch, Yvette; Katz, Seth S.; Munford, Robert S.; Elsbach, Peter; Weiss, Jerrold

1999-01-01

The extent to which the mammalian host is capable of enzymatic degradation and detoxification of bacterial lipopolysaccharides (LPS) is still unknown. Partial deacylation of LPS by the enzyme acyloxyacyl hydrolase (AOAH) provides such a mechanism, but its participation in the disposal of LPS under physiological conditions has not been established. In this study, deacylation of isolated radiolabeled LPS by both cellular and extracellular components of a sterile inflammatory peritoneal exudate elicited in rabbits was examined ex vivo. AOAH-like activity, tested under artificial conditions (pH 5.4, 0.1% Triton X-100), was evident in all components of the exudate (mononuclear cells [MNC] > polymorphonuclear leukocytes [PMN] > inflammatory [ascitic] fluid [AF]). Under more physiological conditions, in a defined medium containing purified LPS-binding protein, the LPS-deacylating activity of MNC greatly exceeded that of PMN. In AF, MNC (but not PMN) also produced rapid and extensive CD14-dependent LPS deacylation. Under these conditions, almost all MNC-associated LPS underwent deacylation within 1 h, a rate greatly exceeding that previously found in any cell type. The remaining extracellular LPS was more slowly subject to CD14-independent deacylation in AF. Quantitative analysis showed a comparable release of laurate and myristate but no release of 3-hydroxymyristate, consistent with an AOAH-like activity. These findings suggest a major role for CD14+ MNC and a secondary role for AF in the deacylation of cell-free LPS at extravascular inflammatory sites. PMID:10377115

Autologous CD34+ cell therapy improves exercise capacity, angina frequency and reduces mortality in no-option refractory angina: a patient-level pooled analysis of randomized double-blinded trials.

PubMed

Henry, Timothy D; Losordo, Douglas W; Traverse, Jay H; Schatz, Richard A; Jolicoeur, E Marc; Schaer, Gary L; Clare, Robert; Chiswell, Karen; White, Christopher J; Fortuin, F David; Kereiakes, Dean J; Zeiher, Andreas M; Sherman, Warren; Hunt, Andrea S; Povsic, Thomas J

2018-01-05

Autologous CD34+ (auto-CD34+) cells represent an attractive option for the treatment of refractory angina. Three double-blinded randomized trials (n = 304) compared intramyocardial (IM) auto-CD34+ cells with IM placebo injections to affect total exercise time (TET), angina frequency (AF), and major adverse cardiac events (MACE). Patient-level data were pooled from the Phase I, Phase II ACT-34, ACT-34 extension, and Phase III RENEW trials to determine the efficacy and safety of auto-CD34+ cells. Treatment effects for TET were analysed using an analysis of covariance mixed-effects model and for AF using Poisson regression in a log linear model with repeated measures. The Kaplan-Meier rate estimates for MACE were compared using the log-rank test. Autologous CD34+ cell therapy improved TET by 46.6 s [3 months, 95% confidence interval (CI) 13.0 s-80.3 s; P = 0.007], 49.5 s (6 months, 95% CI 9.3-89.7; P = 0.016), and 44.7 s (12 months, 95% CI - 2.7 s-92.1 s; P = 0.065). The relative frequency of angina was 0.78 (95% CI 0.63-0.98; P = 0.032), 0.66 (0.48-0.91; P = 0.012), and 0.58 (0.38-0.88; P = 0.011) at 3-, 6- and 12-months in auto-CD34+ compared with placebo patients. Results remained concordant when analysed by treatment received and when confined to the Phase III dose of 1 × 105 cells/kg. Autologous CD34 + cell therapy significantly decreased mortality (12.1% vs. 2.5%; P = 0.0025) and numerically reduced MACE (38.9% vs. 30.0; P = 0.14) at 24 months. Treatment with auto-CD34+ cells resulted in clinically meaningful durable improvements in TET and AF at 3-, 6- and 12-months, as well as a reduction in 24-month mortality in this patient-level meta-analysis. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

Code of Federal Regulations, 2011 CFR

2011-10-01

.... 06460. FRA identification Nos. FRA-ATK-TL-3895-1, FRA-ATK-TL-4491-2, FRA-ATK-TL-4491-3, and FRA-ATK-TL...-300-C (steady burn), and FRA-MEC-MCD-300-F (flasher). 3. Manufacturer: American Electronics, Inc., 1..., Milford, Conn. 06460. FRA identification Nos. FRA-ATSF-TL-875-150, FRA-ATSF-TL-875-60, FRA-ATSF-TL-875...

49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

Code of Federal Regulations, 2013 CFR

2013-10-01

.... 06460. FRA identification Nos. FRA-ATK-TL-3895-1, FRA-ATK-TL-4491-2, FRA-ATK-TL-4491-3, and FRA-ATK-TL...-300-C (steady burn), and FRA-MEC-MCD-300-F (flasher). 3. Manufacturer: American Electronics, Inc., 1..., Milford, Conn. 06460. FRA identification Nos. FRA-ATSF-TL-875-150, FRA-ATSF-TL-875-60, FRA-ATSF-TL-875...

49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

Code of Federal Regulations, 2010 CFR

2010-10-01

.... 06460. FRA identification Nos. FRA-ATK-TL-3895-1, FRA-ATK-TL-4491-2, FRA-ATK-TL-4491-3, and FRA-ATK-TL...-300-C (steady burn), and FRA-MEC-MCD-300-F (flasher). 3. Manufacturer: American Electronics, Inc., 1..., Milford, Conn. 06460. FRA identification Nos. FRA-ATSF-TL-875-150, FRA-ATSF-TL-875-60, FRA-ATSF-TL-875...

49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

Code of Federal Regulations, 2012 CFR

2012-10-01

.... 06460. FRA identification Nos. FRA-ATK-TL-3895-1, FRA-ATK-TL-4491-2, FRA-ATK-TL-4491-3, and FRA-ATK-TL...-300-C (steady burn), and FRA-MEC-MCD-300-F (flasher). 3. Manufacturer: American Electronics, Inc., 1..., Milford, Conn. 06460. FRA identification Nos. FRA-ATSF-TL-875-150, FRA-ATSF-TL-875-60, FRA-ATSF-TL-875...

49 CFR Appendix B to Part 221 - Approved Rear End Marking Devices

Code of Federal Regulations, 2014 CFR

2014-10-01

.... 06460. FRA identification Nos. FRA-ATK-TL-3895-1, FRA-ATK-TL-4491-2, FRA-ATK-TL-4491-3, and FRA-ATK-TL...-300-C (steady burn), and FRA-MEC-MCD-300-F (flasher). 3. Manufacturer: American Electronics, Inc., 1..., Milford, Conn. 06460. FRA identification Nos. FRA-ATSF-TL-875-150, FRA-ATSF-TL-875-60, FRA-ATSF-TL-875...

Aflatoxin levels, plasma vitamins A and E concentrations, and their association with HIV and hepatitis B virus infections in Ghanaians: a cross-sectional study

PubMed Central

2011-01-01

Background Micronutrient deficiencies occur commonly in people infected with the human immunodeficiency virus. Since aflatoxin exposure also results in reduced levels of several micronutrients, HIV and aflatoxin may work synergistically to increase micronutrient deficiencies. However, there has been no report on the association between aflatoxin exposure and micronutrient deficiencies in HIV-infected people. We measured aflatoxin B1 albumin (AF-ALB) adduct levels and vitamins A and E concentrations in the plasma of HIV-positive and HIV-negative Ghanaians and examined the association of vitamins A and E with HIV status, aflatoxin levels and hepatitis B virus (HBV) infection. Methods A cross-sectional study was conducted in which participants completed a demographic survey and gave a 20 mL blood sample for analysis of AF-ALB levels, vitamins A and E concentrations, CD4 counts, HIV viral load and HBV infection. Results HIV-infected participants had significantly higher AF-ALB levels (median for HIV-positive and HIV-negative participants was 0.93 and 0.80 pmol/mg albumin, respectively; p <0.01) and significantly lower levels of vitamin A (-16.94 μg/dL; p <0.0001) and vitamin E (-0.22 mg/dL; p <0.001). For the total study group, higher AF-ALB was associated with significantly lower vitamin A (-4.83 μg/dL for every 0.1 pmol/mg increase in AF-ALB). HBV-infected people had significantly lower vitamin A (-5.66 μg/dL; p = 0.01). Vitamins A and E levels were inversely associated with HIV viral load (p = 0.02 for each), and low vitamin E was associated with lower CD4 counts (p = 0.004). Conclusions Our finding of the significant decrease in vitamin A associated with AF-ALB suggests that aflatoxin exposure significantly compromises the micronutrient status of people who are already facing overwhelming health problems, including HIV infection. PMID:22078415

Impact of Cryopreservation on Caprine Fetal Adnexa Derived Stem Cells and Its Evaluation for Growth Kinetics, Phenotypic Characterization, and Wound Healing Potential in Xenogenic Rat Model.

PubMed

Somal, Anjali; Bhat, Irfan A; B, Indu; Singh, Anuj P; Panda, Bibhudatta S K; Desingu, Perumal A; Pandey, Sriti; Bharti, Mukesh K; Pal, Amar; Saikumar, Guttula; Chandra, Vikash; Sharma, Guttula Taru

2017-08-01

This study was conducted to know the impact of cryopreservation on caprine fetal adnexa derived mesenchymal stem cells (MSCs) on the basic stem cell characteristics. Gravid caprine uteri (2-3 months) were collected from local abattoir to derive (amniotic fluid [cAF], amniotic sac [cAS], Wharton's jelly [cWJ], and cord blood [cCB]) MSCs and expanded in vitro. Cells were cryopreserved at 3rd passage (P3) using 10% DMSO. Post-thaw viability and cellular properties were assessed. Cells were expanded to determine growth kinetics, tri-lineage differentiation, localization, and molecular expression of MSCs and pluripotency markers; thereafter, these cells were transplanted in the full-thickness (2 × 2cm 2 ) rat skin wound to determine their wound healing potential. The post-thaw (pt) growth kinetics study suggested that cWJ MSCs expanded more rapidly with faster population doubling time (PDT) than that of other fetal adnexa MSCs. The relative mRNA expression of surface antigens (CD73, CD90, and CD 105) and pluripotency markers (Oct4, KLF, and cMyc) was higher in cWJ MSCs in comparison to cAS, cAF, and cCB MSCs post-thaw. The percent wound contraction on 7th day was more than 50% for all the MSC-treated groups (pre and post-thaw), against 39.55% in the control group. On day 28th, 99% and more wound contraction was observed in cAF, cAF-pt, cAS-pt, cWJ, cWJ-pt, and cCB, MSCs with better scores for epithelization, neovascularization, and collagen characteristics at a non-significant level. It is concluded that these MSCs could be successfully cryopreserved without altering their stemness and wound healing properties. J. Cell. Physiol. 232: 2186-2200, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Platelet reactivity and mean platelet volume as risk markers of thrombogenesis in atrial fibrillation.

PubMed

Makowski, Marcin; Smorag, Ireneusz; Makowska, Joanna; Bissinger, Andrzej; Grycewicz, Tomasz; Paśnik, Jarek; Kidawa, Michal; Lubiński, Andrzej; Zielińska, Marzenna; Baj, Zbigniew

2017-05-15

Atrial fibrillation (AF) is associated with increased risk of thromboembolic complications. One of the markers of the increased risk of hypercoagulable state is platelet hyperreactivity. The aim of the study was to assess impact of arrhythmia on platelet reactivity. The study included 36 (mean age 48,3; range 21-60) male patients with lone atrial fibrillation, with exclusion of concomitant diseases known to trigger hypercoagulable state. The AF patients underwent cardioversion to restore sinus rhythm and were subsequently under observation for 1month. Echocardiography, ECG and blood collection was performed before cardioversion (T0) and 4weeks after successful cardioversion (T1). During the study period patients have been contacted and examined every week and 24h ECG monitoring was performed. Platelet reactivity was assessed based on changes of CD62 and CD42b expression on platelet surface after stimulation with thrombin. Also changes in MPV were assessed. In all patients sinus rhythm was maintained at the end of the study period, however in 14 patients recurrences of AF were observed, confirmed by 24h ECG monitoring (atrial fibrillation recurrence group - AFR) and 22 patients maintained sinus rhythm throughout the whole study period (SR group). Mean fluorescence intensity (MFI) of CD62 on thrombin stimulated platelets decreased significantly 4weeks after electrical cardioversion as compared to T0 (48.04±22.42 vs 41.47±16.03; p<0.01). Also MFI of CD42b on thrombin stimulated platelets decreased significantly 4weeks after electrical cardioversion as compared to T0 (22.16±10.82 vs 12.06±5.99; p<0.0001). Platelets reactivity estimated by CD 62 expression in SR group decreased significantly after 4weeks observation (58.01±15.26 vs 46.57±13.44; p<0.001) opposite to AFR group 35.66±21.87 vs 34.54±16.4; p-ns). Moreover there were significant differences between basal reactivity during AF between SR and AFR groups (58.01±15.26 vs 35.66±21.87; p-0.01). MFI of CD42b on thrombin stimulated platelets decreased significantly both in AFR and SR groups (22.05±11.36 vs 13.8±6.03; p<0.001 and 21.87±14.18 vs 10.04±5.09; p<0005). MPV decreased significantly 4weeks after electrical cardioversion as compared to T0 (8.81±0.19 vs 8.42±0.14; p<0.0001). The changes of platelet reactivity to thrombin observed after restoration of sinus rhythm in patients prove that arrhythmia intrinsically leads to increased reactivity of platelets. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Cluster of Genes That Encode Positive and Negative Elements Influencing Filament Length in a Heterocyst-Forming Cyanobacterium

PubMed Central

Merino-Puerto, Victoria; Herrero, Antonia

2013-01-01

The filamentous, heterocyst-forming cyanobacteria perform oxygenic photosynthesis in vegetative cells and nitrogen fixation in heterocysts, and their filaments can be hundreds of cells long. In the model heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120, the genes in the fraC-fraD-fraE operon are required for filament integrity mainly under conditions of nitrogen deprivation. The fraC operon transcript partially overlaps gene all2395, which lies in the opposite DNA strand and ends 1 bp beyond fraE. Gene all2395 produces transcripts of 1.35 kb (major transcript) and 2.2 kb (minor transcript) that overlap fraE and whose expression is dependent on the N-control transcription factor NtcA. Insertion of a gene cassette containing transcriptional terminators between fraE and all2395 prevented production of the antisense RNAs and resulted in an increased length of the cyanobacterial filaments. Deletion of all2395 resulted in a larger increase of filament length and in impaired growth, mainly under N2-fixing conditions and specifically on solid medium. We denote all2395 the fraF gene, which encodes a protein restricting filament length. A FraF-green fluorescent protein (GFP) fusion protein accumulated significantly in heterocysts. Similar to some heterocyst differentiation-related proteins such as HglK, HetL, and PatL, FraF is a pentapeptide repeat protein. We conclude that the fraC-fraD-fraE←fraF gene cluster (where the arrow indicates a change in orientation), in which cis antisense RNAs are produced, regulates morphology by encoding proteins that influence positively (FraC, FraD, FraE) or negatively (FraF) the length of the filament mainly under conditions of nitrogen deprivation. This gene cluster is often conserved in heterocyst-forming cyanobacteria. PMID:23813733

Sorption of sulphamethoxazole by the biochars derived from rice straw and alligator flag.

PubMed

Li, Tingqiang; Han, Xuan; Liang, Chengfeng; Shohag, M J I; Yang, Xiaoe

2015-01-01

The sorption ability of sulphamethoxazole (SMX) by biochar derived from rice straw (RS) and alligator flag (AF) at 600°C was studied to assess the ability of biochar as adsorbent to remove SMX from aqueous solution. The results indicated that sorption of SMX by biochars was well described using the Langmuir equation (R2>0.94), and the maximum sorption parameter (Q) of RS (3650 mg kg(-1)) was much higher than that of AF (1963 mg kg(-1)). Temperature had no effect on SMX sorption by biochars, while thermodynamics analysis indicated that the sorption of SMX on both biochars was a spontaneous physical process. The d 250 RS (diameter of RS sieved through 250 µm) and d 150 AF (diameter of AF sieved through 150 µm) showed excellent sorption ability for SMX. The sorption amount of RS was larger than that of AF when pH<7, whereas, the sorption amount of AF surpassed RS when pH≥7. The presence of Cu2+ and/or Cd2+ ion at low concentrations (20 mg L(-1)) significantly (P<0.05) increased the sorption of SMX on both RS and AF. Our study confirms that biochar derived from the wetland plants could be used as effective adsorbents to remove SMX from aqueous solution.

Microenvironment Determines Lineage Fate in a Human Model of MLL-AF9 Leukemia

PubMed Central

Wei, Junping; Wunderlich, Mark; Fox, Catherine; Alvarez, Sara; Cigudosa, Juan C.; Wilhelm, Jamie S.; Zheng, Yi; Cancelas, Jose A.; Gu, Yi; Jansen, Michael; DiMartino, Jorge F.; Mulloy, James C.

2008-01-01

Summary Faithful modeling of mixed lineage leukemia in murine cells has been difficult to achieve. We show that expression of MLL-AF9 in human CD34+ cells induces acute myeloid, lymphoid or mixed lineage leukemia in immunodeficient mice. Some leukemia stem cells (LSC) were multipotent and could be lineage directed by altering either the growth factors or the recipient strain of mouse, highlighting the importance of microenviromental cues. Other LSC were strictly lineage committed, demonstrating the heterogeneity of the stem cell compartment in MLL disease. Targeting the Rac signaling pathway by pharmacologic or genetic means resulted in rapid and specific apoptosis of MLL-AF9 cells, suggesting that the Rac signaling pathway may be a valid therapeutic target in MLL-rearranged AML. PMID:18538732

Fra-1 promotes growth and survival in RAS-transformed thyroid cells by controlling cyclin A transcription

PubMed Central

Casalino, Laura; Bakiri, Latifa; Talotta, Francesco; Weitzman, Jonathan B; Fusco, Alfredo; Yaniv, Moshe; Verde, Pasquale

2007-01-01

Fra-1 is frequently overexpressed in epithelial cancers and implicated in invasiveness. We previously showed that Fra-1 plays crucial roles in RAS transformation in rat thyroid cells and mouse fibroblasts. Here, we report a novel role for Fra-1 as a regulator of mitotic progression in RAS-transformed thyroid cells. Fra-1 expression and phosphorylation are regulated during the cell cycle, peaking at G2/M. Knockdown of Fra-1 caused a proliferative block and apoptosis. Although most Fra-1-knockdown cells accumulated in G2, a fraction of cells entering M-phase underwent abortive cell division and exhibited hallmarks of genomic instability (micronuclei, lagging chromosomes and anaphase bridges). Furthermore, we established a link between Fra-1 and the cell-cycle machinery by identifying cyclin A as a novel transcriptional target of Fra-1. During the cell cycle, Fra-1 was recruited to the cyclin A gene (ccna2) promoter, binding to previously unidentified AP-1 sites and the CRE. Fra-1 also induced the expression of JunB, which in turn interacts with the cyclin A promoter. Hence, Fra-1 induction is important in thyroid tumorigenesis, critically regulating cyclin expression and cell-cycle progression. PMID:17347653

Physical interaction between the strawberry allergen Fra a 1 and an associated partner FaAP: Interaction of Fra a 1 proteins and FaAP.

PubMed

Franz-Oberdorf, Katrin; Langer, Andreas; Strasser, Ralf; Isono, Erika; Ranftl, Quirin L; Wunschel, Christian; Schwab, Wilfried

2017-10-01

The strawberry fruit allergens Fra a 1.01E, Fra a 1.02 and Fra a 1.03 belong to the group of pathogenesis-related 10 (PR-10) proteins and are homologs of the major birch pollen Bet v 1 and apple allergen Mal d 1. Bet v 1 related proteins are the most extensively studied allergens but their physiological function in planta remains elusive. Since Mal d 1-Associated Protein has been previously identified as interaction partner of Mal d 1 we studied the binding of the orthologous Fra a 1-Associated Protein (FaAP) to Fra a 1.01E/1.02/1.03. As the C-terminal sequence of FaAP showed strong auto-activation activity in yeast 2-hybrid analysis a novel time resolved DNA-switching system was successfully applied. Fra a 1.01E, Fra a 1.02, and Fra a 1.03 bind to FaAP with K D of 4.5 ± 1.1, 15 ± 3, and 11 ± 2 nM, respectively. Fra a 1.01E forms a dimer, whereas Fra a 1.02 and Fra a 1.03 bind as monomer. The results imply that PR-10 proteins might be integrated into a protein-interaction network and FaAP binding appears to be essential for the physiological function of the Fra a 1 proteins. © 2017 Wiley Periodicals, Inc.

Free ferulic acid uptake in lactating cows.

PubMed

Soberon, M A; Cherney, J H; Liu, R H; Ross, D A; Cherney, D J R

2012-11-01

Ferulic acid (FRA), a phenolic compound with antioxidant and anticancer activities, naturally occurs in plants as a lignin precursor. Many veins of research have been devoted to releasing FRA from the lignin complex to improve digestibility of ruminant feeds. Thus, the objective of this research was to investigate the transfer of a given dosage of the free form of FRA into the milk of dairy cattle. Six mid- to late-lactation Holstein cows at the Cornell Research Farm (Harford, NY) were given 14-d adaptation to diet and stall position. Ad libitum access to a total mixed ration based on haylage and maize silage (31.1% neutral detergent fiber containing 5.52 mg of FRA/g) was provided during the study. A crossover design was implemented so that each cow alternated weekly between FRA-dosed and control. On d 1, jugular cannulas and urine catheters were placed in all cows. On d 2, FRA-dosed cows received a single dosage of 150 g of pure FRA powder at 0830 h via their fistula (n=4) or a balling gun for nonfistulated cows (n=2). Plasma, urine, feces, feed, orts, milk, and rumen fluid were sampled intensively for the next 36 h and analyzed for FRA concentration. On d 8, the cows crossed over and the experiment was repeated. When compared with the control, FRA administration did not have an effect on dry matter intake, milk yield, milk fat yield, milk protein yield, somatic cell count, or neutral detergent fiber content of orts and feces. The concentration of FRA in the feces did not change as a result of FRA dosage. As expected, FRA concentration increased dramatically upon FRA dosage and decreased over time until returning to basal levels in rumen fluid (4 h after dosage), plasma (5.5 h after dosage), urine (10 h after dosage), and milk (14 h after dosage). Baseline values for FRA in urine and rumen fluid were variable among cows and had an effect on FRA concentration in FRA-dosed cows. From this study, it is observed that orally ingested FRA can be transported into the milk and that the physiological transfer of FRA occurs from rumen to milk within 6.5 h or the first milking after dosage. Ferulic acid may affect the functionality of milk due to its antioxidant, anticancer, and antibacterial activities. Future research will be required to elucidate whether FRA in milk is bioavailable and bioactive, and to evaluate the complete sensory and microbiological effects of increased FRA and FRA degradation products in milk. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Induction of a glucocorticoid-sensitive F1-anti-parental mechanism that affects engraftment during graft-versus-host disease.

PubMed

You-Ten, K E; Seemayer, T A; Wisse, B; Bertley, F M; Lapp, W S

1995-07-01

Studies have shown that graft-vs-host disease (GVHD) in animal models induces persistent elevated levels of circulating adrenal glucocorticoids. In this report, we investigated the effects of endogenous glucocorticoids on the outcome of GVHD by adrenalectomizing (ADX) unirradiated (C57BL/6 x A)F1 (B6AF1) mice before GVHD induction. GVHD was induced by injection of 20 x 10(6) A strain parental lymphoid cells into B6AF1 mice. Our results demonstrated that non-ADX recipient mice experienced features characteristic of GVHD on day 13, which became progressively more severe by days 18 to 21. The GVHD features included severe immunosuppression, reversal in the host splenic CD4+/CD8+ ratio, histopathologic lesions in different tissues, and high parental cell chimerism in the spleens and lymph nodes. In contrast, ADX F1 recipient mice experienced GVHD features on day 13 similar to their non-ADX counterparts; however, ADX animals recovered rapidly from GVHD by days 18 to 21. Flow cytometry showed that, although a relatively high frequency of parental cells was detected in the spleens and lymph nodes of ADX mice on day 13, nearly all of the parental cells in the peripheral lymphoid organs disappeared on days 18 to 21, the time of recovery from GVHD. The marked reduction of parental cells and recovery from GVHD were prevented by treating ADX F1 mice with either exogenous glucocorticoid, anti-asialoGM1, or anti-CD8, but not anti-NK1.1 Ab. These results suggest that a dramatic recovery from GVHD was induced by a cell-mediated, steroid-sensitive F1-anti-parental mechanism. The F1-anti-parental phenomenon described herein is different from classical hybrid resistance.

Test Message Generator and Controller for AFSATCOM Testing.

DTIC Science & Technology

1983-03-01

RW o Sk;I Af IiAA C 1 I SYNDET -JZDf CXT2/ gzl 3M52 140A 2 P7 54 1LPro/ I, RIOa Itw I 4"A 4 RZi o I~~- Co-P a F ’~T14 1W Cf14K A460 hi ,2 L PFa/ tip II...W CZt / -o 0U(zuouC. go P U A00. OC -c )toM f w z)0 C 0 Z0w 0 C)~~~- -- 4 -0- - --- 4 4 En 04I-.4z- N N N-- 0.44- N -44 L A A AA A A A A A A A A AA A A...C3 70 02 ....... 0290=77 AF 23 77 C9 21 AC 04 CD 23 02 I1 00 00 CD E7 .. #..!...# ...... 02AO=02 FE FF CA 95 02 FE OD CA CO 02 47 OE 04 7B 17

Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.

PubMed

Mulligan, Jennifer K; Pasquini, Whitney N; Carroll, William W; Williamson, Tucker; Reaves, Nicholas; Patel, Kunal J; Mappus, Elliott; Schlosser, Rodney J; Atkinson, Carl

2017-01-01

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS). Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined. Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A. VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Fe2+ chelator proferrorosamine A: a gene cluster of Erwinia rhapontici P45 involved in its synthesis and its impact on growth of Erwinia amylovora CFBP1430.

PubMed

Born, Yannick; Remus-Emsermann, Mitja N P; Bieri, Marco; Kamber, Tim; Piel, Jörn; Pelludat, Cosima

2016-02-01

Proferrorosamine A (proFRA) is an iron (Fe2+) chelator produced by the opportunistic plant pathogen Erwinia rhapontici P45. To identify genes involved in proFRA synthesis, transposon mutagenesis was performed. The identified 9.3 kb gene cluster, comprising seven genes, designated rosA-rosG, encodes proteins that are involved in proFRA synthesis. Based on gene homologies, a biosynthetic pathway model for proFRA is proposed. To obtain a better understanding of the effect of proFRA on non-proFRA producing bacteria, E. rhapontici P45 was co-cultured with Erwinia amylovora CFBP1430, a fire-blight-causing plant pathogen. E. rhapontici P45, but not corresponding proFRA-negative mutants, led to a pink coloration of E. amylovora CFBP1430 colonies on King's B agar, indicating accumulation of the proFRA-iron complex ferrorosamine, and growth inhibition in vitro. By saturating proFRA-containing extracts with Fe2+, the inhibitory effect was neutralized, suggesting that the iron-chelating capability of proFRA is responsible for the growth inhibition of E. amylovora CFBP1430.

Expression of Fra-1 in human hepatocellular carcinoma and its prognostic significance.

PubMed

Gao, Xiao-Qiang; Ge, Yong-Sheng; Shu, Qing-Hua; Ma, Hua-Xing

2017-06-01

This study aimed to explore the clinical significance and prognostic value of Fra-1 in hepatocellular carcinoma patients after curative resection. Fra-1 expression was investigated using a combination of techniques: immunohistochemistry for 66 samples of hepatocellular carcinoma and quantitative real-time polymerase chain reaction and western blotting assays for 19 matched hepatocellular carcinoma specimens. Fra-1 was present in 38 of 66 (57.6%) tumor tissues, with intense staining in the nuclei. There was also positive staining in 14 of 66 (21.2%) adjacent peritumoral tissues, with weak staining in the cytoplasm. Quantitative real-time polymerase chain reaction and western blotting assays confirmed higher expression of Fra-1 messenger RNA and Fra-1 protein in tumor tissues than adjacent non-tumor tissues for 19 hepatocellular carcinoma samples (p < 0.001). Positive expression of Fra-1 was significantly related to vascular invasion and serum alpha-fetoprotein. Kaplan-Meier survival analysis found that overexpressed Fra-1 was correlated with poor overall survival and disease-free survival. Multivariate analysis identified Fra-1 as an independent prognostic factor. Fra-1 may be involved in the progress of hepatocellular carcinoma and could be a promising molecular candidate in the diagnosis and treatment of hepatocellular carcinoma.

Oxidant-Induced Cell Death and Nrf2-Dependent Antioxidative Response Are Controlled by Fra-1/AP-1

PubMed Central

Vaz, Michelle; Machireddy, Narsa; Irving, Ashley; Potteti, Haranatha R.; Chevalier, Karinne; Kalvakolanu, Dhananjaya

2012-01-01

AP-1 (Jun/Fos) transcription factors play key roles in various biological processes, including cell death. Here we report a novel role for Fra-1 in oxidant-induced cell death controlled by modulating antioxidant gene expression. Fra-1-deficient (Fra-1Δ/Δ) mouse embryonic fibroblasts (MEFs) and primary lung fibroblasts (PLFs) were remarkably resistant to H2O2- and diquat-induced cell death, compared to their wild-type (Fra-1+/+) counterparts. Fra-1 deficiency ablated oxidant-induced mitochondrion-dependent apoptosis. Fra-1Δ/Δ cells had elevated basal levels of antioxidant enzymes and intracellular glutathione (GSH), which were further stimulated by oxidants. Loss of Fra-1 led to an increased half-life of transcription factor Nrf2 and increased recruitment of this protein to the promoters of antioxidant genes and increased their expression. Depletion of intracellular GSH or RNA interference (RNAi)-mediated knockdown of Nqo1, Hmox1, and Nrf2 restored oxidant-induced cell death in Fra-1Δ/Δ cells. Thus, Fra-1 appears to increase susceptibility to oxidants and promotes cell death by attenuating Nrf2-driven antioxidant responses. PMID:22393254

Role of Fos-related antigen 1 in the progression and prognosis of ductal breast carcinoma

PubMed Central

Logullo, Angela Flavia; Stiepcich, Mônica Maria Ágata; de Toledo Osório, Cintia Aparecida Bueno; Nonogaki, Sueli; Pasini, Fátima Solange; Rocha, Rafael Malagoli; Soares, Fernando Augusto; Brentani, Maria M

2011-01-01

Aims Fos-related antigen 1 (Fra-1) is a member of the activator protein 1 (AP-1) transcription factor family. Our objective was to evaluate the role of Fra-1 expression in breast carcinoma progression and prognosis. Methods and results Fra-1 expression was investigated by immunohistochemistry in two tissue microarrays containing, respectively, 85 ductal carcinoma in situ (DCIS) and 771 invasive ductal carcinoma (IDC) samples. Staining was observed in the nucleus and cytoplasm of the carcinomas, but only nuclear staining was considered to be positive. Fibroblasts associated with IDC were also Fra-1-positive. The frequency of Fra-1 positivity in IDC (22.8%) was lower than that in DCIS (42.2%). No association was found between Fra-1 and clinico-pathological variables in DCIS. In IDC, Fra-1 expression correlated with aggressive phenotype markers, including: high grade, oestrogen receptor negativity and human epidermal growth factor receptor 2 (HER-2) positivity (P = 0.001, 0.015 and 0.004, respectively), and marginally with the presence of metastasis (P = 0.07). Fra-1 was more frequently positive in basal-like (34%) and in HER-2-positive (38.5%) subtypes than in luminal subtypes. Fra-1 presence did not correlate with survival. Conclusions A high frequency of Fra-1 in DCIS tumours may be associated with early events in breast carcinogenesis. Although Fra-1 expression correlated with features of a more aggressive phenotype in IDC, no relationship with overall survival was found. PMID:21371080

Requirement of Fra proteins for communication channels between cells in the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120.

PubMed

Omairi-Nasser, Amin; Mariscal, Vicente; Austin, Jotham R; Haselkorn, Robert

2015-08-11

The filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 differentiates specialized cells, heterocysts, that fix atmospheric nitrogen and transfer the fixed nitrogen to adjacent vegetative cells. Reciprocally, vegetative cells transfer fixed carbon to heterocysts. Several routes have been described for metabolite exchange within the filament, one of which involves communicating channels that penetrate the septum between adjacent cells. Several fra gene mutants were isolated 25 y ago on the basis of their phenotypes: inability to fix nitrogen and fragmentation of filaments upon transfer from N+ to N- media. Cryopreservation combined with electron tomography were used to investigate the role of three fra gene products in channel formation. FraC and FraG are clearly involved in channel formation, whereas FraD has a minor part. Additionally, FraG was located close to the cytoplasmic membrane and in the heterocyst neck, using immunogold labeling with antibody raised to the N-terminal domain of the FraG protein.

Terminal epidermal differentiation is regulated by the interaction of Fra-2/AP-1 with Ezh2 and ERK1/2

PubMed Central

Wurm, Stefanie; Zhang, Jisheng; Guinea-Viniegra, Juan; García, Fernando; Muñoz, Javier; Bakiri, Latifa; Ezhkova, Elena

2015-01-01

Altered epidermal differentiation characterizes numerous skin diseases affecting >25% of the human population. Here we identified Fra-2/AP-1 as a key regulator of terminal epidermal differentiation. Epithelial-restricted, ectopic expression of Fra-2 induced expression of epidermal differentiation genes located within the epidermal differentiation complex (EDC). Moreover, in a papilloma-prone background, a reduced tumor burden was observed due to precocious keratinocyte differentiation by Fra-2 expression. Importantly, loss of Fra-2 in suprabasal keratinocytes is sufficient to cause skin barrier defects due to reduced expression of differentiation genes. Mechanistically, Fra-2 binds and transcriptionally regulates EDC gene promoters, which are co-occupied by the transcriptional repressor Ezh2. Fra-2 remains transcriptionally inactive in nondifferentiated keratinocytes, where it was found monomethylated and dimethylated on Lys104 and interacted with Ezh2. Upon keratinocyte differentiation, Fra-2 is C-terminally phosphorylated on Ser320 and Thr322 by ERK1/2, leading to transcriptional activation. Thus, the induction of epidermal differentiation by Fra-2 is controlled by a dual mechanism involving Ezh2-dependent methylation and activation by ERK1/2-dependent phosphorylation. PMID:25547114

Fra a 1.02 Is the Most Potent Isoform of the Bet v 1-like Allergen in Strawberry Fruit.

PubMed

Franz-Oberdorf, Katrin; Eberlein, Bernadette; Edelmann, Kathrin; Hücherig, Stephanie; Besbes, Fatma; Darsow, Ulf; Ring, Johannes; Schwab, Wilfried

2016-05-11

The strawberry fruit proteins Fra a 1.01E-1.08 are homologues of the major birch pollen allergen Bet v 1. Three of the proteins are known to have essential biological functions in pigment formation during fruit ripening and seem to be responsible for allergic reactions to strawberry fruit. We evaluated the cross-reactive allergenic potential of these putative strawberry allergens in patients allergic to birch pollen. Activation of basophils of eight atopic patients was studied using different concentrations of Fra a 1 isoforms. Bet v 1a was used as control and as atopic patient selection criterion. Although Fra a 1.01E-1.08 have amino acid sequence identities of 74.5-97.5% with Fra a 1.02, the basophil activation mediated by the eight Fra a 1 proteins differed substantially. Fra a 1.03 and Fra a 1.02 showed the highest activation of basophils, 73 and 66% of total basophils, respectively. On the basis of the high relative expression of the gene Fra a 1.02 in ripe strawberry fruits of allergenic varieties, Fra a 1.02 was identified as the main strawberry allergen of the Bet v 1 superfamily. Knowledge of the allergenic potential of Fra a 1.02/1.03 will help to improve food safety and can serve as a valuable marker for the development of red-fruited hypoallergenic strawberry cultivars.

77 FR 43646 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... Railway (CP) has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance extension... Number FRA-2012-0029. The Confidential Close Call Reporting System (C3RS) pilot project for the CP Portage, WI, terminal was initially approved by FRA on March 3, 2008. In Docket Number FRA-2007-0008, CP...

Atrial Electromechanical Properties in Inflammatory Bowel Disease.

PubMed

Efe, Tolga Han; Cimen, Tolga; Ertem, Ahmet Goktug; Coskun, Yusuf; Bilgin, Murat; Sahan, Haluk Furkan; Pamukcu, Hilal Erken; Yayla, Cagri; Sunman, Hamza; Yuksel, Ilhami; Yeter, Ekrem

2016-09-01

There is much evidence linking inflammation to the initiation and continuation of atrial fibrillation (AF). Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic systemic inflammatory disorders. Atrial electromechanical delay (EMD) has been known as an early marker of AF. The objectives of this study were to evaluate the atrial electromechanical properties in patients with IBD. Fifty-two patients with IBD and 26 healthy controls were recruited in the study. Twenty-five of patients with IBD were on active period, and the remaining 27 were on remission period. Atrial electromechanical properties were measured by using transthoracic echocardiography and tissue Doppler imaging and simultaneous surface ECG recording. Interatrial EMD, left intraatrial EMD, and right intraatrial EMD were calculated. Patients on activation with IBD had significantly prolonged left and right intraatrial EMDs and interatrial EMD compared to patients on remission (P = 0.048, P = 0.036, P < 0.001, respectively) and healthy controls (P < 0.001, for all comparisons). Left and right intraatrial EMDs and interatrial EMD were also found to be higher when patients on remission with IBD compared with healthy controls. No statistical difference was observed between UC and CD in terms of inter- and intraatrial EMDs. Atrial electromechanical conduction is prolonged in IBD, and exposure to chronic inflammation may lead to structural and electrophysiological changes in the atrial tissue that causes slow conduction. Measurement of atrial EMD parameters might be used to predict the risk for the development of AF in patients with IBD. © 2016, Wiley Periodicals, Inc.

Targeted Approaches to Overcoming Endocrine Resistance in Breast Cancer

DTIC Science & Technology

2012-08-01

kinase B CD049340 BIRC5 Effector cell peptidase receptor 1 NM_001012271 BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog AF053305 CDC20 Cell...P ≤ 0.0001). Among these were BUB1 (bud- ding uninhibited by benzimidazoles 1 homolog), BIRC5/ Survivin, CDCA8 (cell division cycle-associated

Department of the Navy Supporting Data for FY 1992/1993 Budget Estimates Submitted to Congress February 1991. Operating Appropriations Navy and Marine Corps

DTIC Science & Technology

1991-02-01

CL a . 0. a.I CL 97C. -4 . =- mW~ = m- r. :v V) r-4cvcvcv o w 0 cd 0 0 m Voo 0, C4 0 E .* 0 czt cv 0"’ cv -o 0 ed bCa ~ O cv wc w cv bo m- c 0. m. cv...C)C - -44 Un % $4, W.. C) )C 4 CL 0 1-4 CD co co C>0 r- 00 ++ W af .~). 4-)4 ~4 ~ nEnS4X I- Q) ED Lo~ - 0 a) r- 41 0) u c 0 -P ua 0 -4 0 ’a r ( - - a...va 6, 48 .- ,0.0 00 000 0 0 O - 00 00 0 0 .0 0 0 00 10 oa U vi I a ’ o 1 1 40 a W-, o0 -a- o 4 .O c 8u oA 44 l*2. 4 * a c u u " : Cl n. a. 00 1 Af Im

Effects of Newcastle Disease Virus Strains AF2240 and V4-UPM on Cytolysis and Apoptosis of Leukemia Cell Lines

PubMed Central

Alabsi, Aied M.; Bakar, Siti Aishah Abu; Ali, Rola; Omar, Abdul Rahman; Bejo, Mohd Hair; Ideris, Aini; Ali, Abdul Manaf

2011-01-01

Newcastle disease virus (NDV) is used as an antineoplastic agent in clinical tumor therapy. It has prompted much interest as an anticancer agent because it can replicate up to 10,000 times better in human cancer cells than in most normal cells. This study was carried out to determine the oncolytic potential of NDV strain AF2240 and V4-UPM on WEHI-3B leukemia cell line. Results from MTT cytotoxicity assay showed that the CD50 values for both strains were 2 and 8 HAU for AF2240 and V4-UPM, respectively. In addition, bromodeoxyuridine (BrdU) and trypan blue dye exclusion assays showed inhibition in cell proliferation after different periods. Increase in the cellular level of caspase-3 and detection of DNA laddering using agarose gel electrophoresis on treated cells with NDV confirmed that the mode of cell death was apoptosis. In addition, flow-cytometry analysis of cellular DNA content showed that the virus caused an increase in the sub-G1 region (apoptosis peaks). In conclusion, NDV strains AF2240 and V4-UPM caused cytolytic effects against WEHI-3B leukemic cell line. PMID:22272097

Monothiol glutaredoxins and A-type proteins: partners in Fe-S cluster trafficking.

PubMed

Mapolelo, Daphne T; Zhang, Bo; Randeniya, Sajini; Albetel, Angela-Nadia; Li, Haoran; Couturier, Jérémy; Outten, Caryn E; Rouhier, Nicolas; Johnson, Michael K

2013-03-07

Monothiol glutaredoxins (Grxs) are proposed to function in Fe-S cluster storage and delivery, based on their ability to exist as apo monomeric forms and dimeric forms containing a subunit-bridging [Fe(2)S(2)](2+) cluster, and to accept [Fe(2)S(2)](2+) clusters from primary scaffold proteins. In addition yeast cytosolic monothiol Grxs interact with Fra2 (Fe repressor of activation-2), to form a heterodimeric complex with a bound [Fe(2)S(2)](2+) cluster that plays a key role in iron sensing and regulation of iron homeostasis. In this work, we report on in vitro UV-visible CD studies of cluster transfer between homodimeric monothiol Grxs and members of the ubiquitous A-type class of Fe-S cluster carrier proteins ((Nif)IscA and SufA). The results reveal rapid, unidirectional, intact and quantitative cluster transfer from the [Fe(2)S(2)](2+) cluster-bound forms of A. thaliana GrxS14, S. cerevisiae Grx3, and A. vinelandii Grx-nif homodimers to A. vinelandii(Nif)IscA and from A. thaliana GrxS14 to A. thaliana SufA1. Coupled with in vivo evidence for interaction between monothiol Grxs and A-type Fe-S cluster carrier proteins, the results indicate that these two classes of proteins work together in cellular Fe-S cluster trafficking. However, cluster transfer is reversed in the presence of Fra2, since the [Fe(2)S(2)](2+) cluster-bound heterodimeric Grx3-Fra2 complex can be formed by intact [Fe(2)S(2)](2+) cluster transfer from (Nif)IscA. The significance of these results for Fe-S cluster biogenesis or repair and the cellular regulation of the Fe-S cluster status are discussed.

49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters C Appendix C to Part 241 Transportation Other Regulations Relating... STATES LOCATIONAL REQUIREMENT FOR DISPATCHING OF UNITED STATES RAIL OPERATIONS Pt. 241, App. C Appendix C...

49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters C Appendix C to Part 241 Transportation Other Regulations Relating... STATES LOCATIONAL REQUIREMENT FOR DISPATCHING OF UNITED STATES RAIL OPERATIONS Pt. 241, App. C Appendix C...

49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters C Appendix C to Part 241 Transportation Other Regulations Relating... STATES LOCATIONAL REQUIREMENT FOR DISPATCHING OF UNITED STATES RAIL OPERATIONS Pt. 241, App. C Appendix C...

The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells

PubMed Central

Grötsch, Bettina; Brachs, Sebastian; Lang, Christiane; Luther, Julia; Derer, Anja; Schlötzer-Schrehardt, Ursula; Bozec, Aline; Fillatreau, Simon; Berberich, Ingolf; Hobeika, Elias; Reth, Michael; Wagner, Erwin F.; Schett, Georg

2014-01-01

The cornerstone of humoral immunity is the differentiation of B cells into antibody-secreting plasma cells. This process is tightly controlled by a regulatory gene network centered on the transcriptional repressor B lymphocyte–induced maturation protein 1 (Blimp1). Proliferation of activated B cells is required to foster Blimp1 expression but needs to be terminated to avoid overshooting immune reactions. Activator protein 1 (AP-1) transcription factors become quickly up-regulated upon B cell activation. We demonstrate that Fra1, a Fos member of AP-1, enhances activation-induced cell death upon induction in activated B cells. Moreover, mice with B cell–specific deletion of Fra1 show enhanced plasma cell differentiation and exacerbated antibody responses. In contrast, transgenic overexpression of Fra1 blocks plasma cell differentiation and immunoglobulin production, which cannot be rescued by Bcl2. On the molecular level, Fra1 represses Blimp1 expression and interferes with binding of the activating AP-1 member c-Fos to the Blimp1 promoter. Conversely, overexpression of c-Fos in Fra1 transgenic B cells releases Blimp1 repression. As Fra1 lacks transcriptional transactivation domains, we propose that Fra1 inhibits Blimp1 expression and negatively controls plasma cell differentiation through binding to the Blimp1 promoter. In summary, we demonstrate that Fra1 negatively controls plasma cell differentiation by repressing Blimp1 expression. PMID:25288397

On the History and Origin of LKFM

NASA Astrophysics Data System (ADS)

Korotev, Randy L.

1998-01-01

Fra Mauro is the name of a geologic formation surrounding the Imbrium Basin of the Moon as well as the name of the region of the Apollo 14 lunar landing site. The formation was named for a 16th century Italian geographer and cartographer. In its original invocation in 1971 by the Apollo Soil Survey (ASS), Fra Mauro basalt was not a crystalline basalt, but the designation of a "compositional group" of impact glasses found in the Apollo 14 soil that were basaltic in composition. The ASS noted the similarity between the Fra Mauro basalt glass composition and sample 14310, an unbrecciated, crystalline Apollo 14 rock that would now be designated an impact melt rock. In 1972 the term Fra Mauro basalt was first applied to a rock, sample 14310, although in related papers, Fra Mauro basaltic glass was equated with KREEP. In 1973 the ASS noted that a wide range of K concentrations occurred among glasses of Fra Mauro basaltic composition in the Apollo 15 regolith. The terms high-K, moderate-K and low-K Fra Mauro first occurred in that context, but always as an adjective. Lock Fra Mauro glasses were those with 0.12 +/- 0.07% K2O, compared with 0.47 +/- 0.17% and 1.1 +/- 0.4% for moderate and high-K Fra Mauro glasses and 0.6% for Apollo 15 KREEP basalt. An important evolutionary step in the concept of low Fra Mauro basalt occurred in 1973 when the composition was first used as a component in a mass-balance (mixing) model for Apollo 16 soils [8,9] and later average highlands crust, despite that the term had not yet been applied to an actual rock sample. The first use of the acronym LKFM occurred in a 1973 paper describing glass compositions in Apollo 16 soil.

High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol

PubMed Central

Cario, Gunnar; Rhein, Peter; Mitlöhner, Rita; Zimmermann, Martin; Bandapalli, Obul R.; Romey, Renja; Moericke, Anja; Ludwig, Wolf-Dieter; Ratei, Richard; Muckenthaler, Martina U.; Kulozik, Andreas E.; Schrappe, Martin; Stanulla, Martin; Karawajew, Leonid

2014-01-01

Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75th percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72±3% versus 86±1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60±8% versus 78±4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22±3% versus 11±1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31±8% versus 11±3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1, MLL/AF4 and BCR/ABL1 rearrangements in B-cell-precursor acute lymphoblastic leukemia (P=0.002 and P=0.025, respectively). Consideration of CD45 expression may serve as an additional stratification tool in BFM-based protocols. (ClinicalTrials.gov identifier: NCT00430118) PMID:23911702

High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.

PubMed

Cario, Gunnar; Rhein, Peter; Mitlöhner, Rita; Zimmermann, Martin; Bandapalli, Obul R; Romey, Renja; Moericke, Anja; Ludwig, Wolf-Dieter; Ratei, Richard; Muckenthaler, Martina U; Kulozik, Andreas E; Schrappe, Martin; Stanulla, Martin; Karawajew, Leonid

2014-01-01

Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75(th) percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72 ± 3% versus 86 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60 ± 8% versus 78 ± 4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22 ± 3% versus 11 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31 ± 8% versus 11 ± 3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1, MLL/AF4 and BCR/ABL1 rearrangements in B-cell-precursor acute lymphoblastic leukemia (P=0.002 and P=0.025, respectively). Consideration of CD45 expression may serve as an additional stratification tool in BFM-based protocols. (ClinicalTrials.gov identifier: NCT00430118).

49 CFR 225.39 - FRA policy on covered data.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., DEPARTMENT OF TRANSPORTATION RAILROAD ACCIDENTS/INCIDENTS: REPORTS CLASSIFICATION, AND INVESTIGATIONS § 225.39 FRA policy on covered data. FRA will not include covered data (as defined in § 225.5) in its...

49 CFR 225.39 - FRA policy on covered data.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., DEPARTMENT OF TRANSPORTATION RAILROAD ACCIDENTS/INCIDENTS: REPORTS CLASSIFICATION, AND INVESTIGATIONS § 225.39 FRA policy on covered data. FRA will not include covered data (as defined in § 225.5) in its...

Focal retrograde amnesia and the episodic-semantic distinction.

PubMed

Wheeler, M A; McMillan, C T

2001-03-01

This article reports a review of focal retrograde amnesia (FRA), or the phenomenon of organically based severe memory loss restricted to retrograde, or pretraumatic, memory. Cases of FRA are classified according to the type of memory loss: episodic, semantic, or both. A few different clusters of the disorder were identified. Lesions to either the anterior temporal lobes or the posterior/visual cortex can result in an FRA that devastates retrograde episodic memory, while having smaller effects on semantic memory. A number of left-hemisphere patients have FRA confined to semantic memory. There are several additional examples of FRA following minor cerebral trauma that disrupts either episodic memory alone or both episodic and semantic memory that are not accompanied by evidence of structural brain lesions. We discuss these different profiles of FRA and their implications for the understanding of memory retrieval.

A Phosphatidylinositol 3-kinase-regulated Akt-independent signaling promotes cigarette smoke-induced FRA-1 expression.

PubMed

Zhang, Qin; Adiseshaiah, Pavan; Kalvakolanu, Dhananjaya V; Reddy, Sekhar P

2006-04-14

The FRA-1 proto-oncogene is overexpressed in a variety of human tumors and is known to up-regulate the expression of genes involved in tumor progression and invasion. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway is also known to regulate these cellular processes. More importantly, respiratory toxicants and carcinogens activate both the PI3K-Akt pathway and FRA-1 expression in human bronchial epithelial (HBE) cells. In this study we investigated a potential link between the PI3K-Akt pathway and the cigarette smoke (CS)-stimulated epidermal growth factor receptor-mediated FRA-1 induction in non-oncogenic HBE cells. Treatment of cells with LY294002, an inhibitor of the PI3K-Akt pathway, completely blocked CS-induced FRA-1 expression. Surprisingly pharmacological inhibition of Akt had no significant effect on CS-induced FRA-1 expression. Likewise the inhibition of protein kinase C zeta, which is a known downstream effector of PI3K, did not alter FRA-1 expression. We found that the PI3K through p21-activated kinase 1 regulates FRA-1 proto-oncogene induction by CS and the subsequent activation of the Elk1 and cAMP-response element-binding protein transcription factors that are bound to the promoter in HBE cells.

[The study on the changes of serum IL- 6, TNF-α and peripheral blood T lymphocyte subsets in the pregnant women during perinatal period].

PubMed

Li, Juan

2011-03-01

To study the change law of serum IL-6, TNF-α and peripheral blood T lymphocyte subsets in the pregnant women during perinatal period. 100 pregnant women in our hospital from November 2009 to October 2010 were selected as research object, and the serum IL-6, TNF-α and peripheral blood T lymphocyte subsets be-fore and at labor onset occurring, after delivery at the first and third day were analyzed and compared. According the study, the serum IL-6 and TNF-aat labor onset occurring were higher than those before labor onset and af-ter delivery at the first and third day , the CD3(+), CD4 (+), CD8(+) and CD4/CD8 decreased first and then increased, all P < 0. 05, there were significant differences. The changes of serum IL-6, TNF-α and peripheral blood T lymphocyte subsets in the pregnant women during perinatal period has a regular pattern, and it is worthy of.

Influence of stimulants on electrodermal studies in Fragile X syndrome.

PubMed

Hagerman, Randi J; Miller, Lucy J; McGrath-Clarke, Jude; Riley, Karen; Goldson, Edward; Harris, Susan W; Simon, Jody; Church, Kelly; Bonnell, Julie; Ognibene, Todd C; McIntosh, Daniel N

2002-05-01

Attention Deficit Hyperactivity Disorder (ADHD) is seen in the majority of children with Fragile X Syndrome (FraX). Previous work has documented an enhanced sweat response to stimuli in children with FraX compared to controls utilizing electrodermal response (EDR) measures. The present study assesses the EDRs both on and off stimulants in 19 children with ADHD and FraX compared to 17 age- and IQ-matched control patients with ADHD and developmental delays. Although the baseline EDRs were comparable between FraX patients and controls, the patients with FraX had a significant decrease in EDR amplitude and number of peaks when treated with stimulants compared to controls. This suggests that patients with FraX are more responsive to the enhancement of inhibitory systems that occur with stimulant use for ADHD. The use of a quantifiable measure, such as EDR, is recommended in future studies of treatment efficacy. Copyright 2002 Wiley-Liss, Inc.

[Cytokine-mediated regulation of expression of Gfi1 and U2afll4 genes activated by T-cells with different differentiation status in vitro].

PubMed

Yurova, K A; Sokhonevich, N A; Khaziakhmatova, O G; Litvinova, L S

2016-01-01

The dose-dependent effects of cytokines (IL-2, IL-7, and IL-15), which have a common g-chain, on mRNA expression of U2afll4 and GFi1 genes involved in regulation of alternative splicing of the Ptprc gene, have been investigated in vitro using T-lymphocyte cultures with different degrees of differentiation. IL-2, IL-7, and IL-15 caused a similar unidirectional inhibitory effect of various severity on restimulated CD45RO+ T-cells exposed to an antigen-independent activation; they caused a dose-dependent decrease of the U2af1l4 gene expression, and an increase of Gfi1 gene expression. This may suggest formation of active forms of the CD45 receptor, and also limitation of the formation of low-molecular short splice variants of the CD45RO receptor. Under conditions of antigen-independent stimulation of naive CD45RA+-cells rIL-7 and IL-15 exhibited opposite effects on U2af1l4 and Gfi1 gene expression. The increase of IL-7 concentrations in the incubation medium of naive cells was accompanied by a decrease in expression of both genes. IL-15 IL-7 exhibited opposite effects. Cytokines possessing a common g-chain (IL-2, IL-7, and IL-15) prevented antigen-independent differentiation of naive T-cells, by preventing the formation of polyclonal "surrogate" cells. In general, the study of the molecular mechanisms of genetic control determining homeostatic processes of T-cells in response to exposure to antigenic or non-antigenic treatments may be important for construction of a general model of self-maintenance and differentiation of immune cells.

Comparison of FRA regulations to international high-speed rail standards.

DOT National Transportation Integrated Search

2013-05-01

This report compares international standards with selected parts of Federal Railroad Administration (FRA) Code of Federal Regulation Title 49 CFR Transportation. The parts were preselected by FRA and are meant to reflect those areas of the regulation...

Long-Term Hematopoietic Engraftment of Congenic Amniotic Fluid Stem Cells After in Utero Intraperitoneal Transplantation to Immune Competent Mice

PubMed Central

Shangaris, Panicos; Loukogeorgakis, Stavros P.; Blundell, Michael P.; Petra, Eleni; Shaw, Steven W.; Ramachandra, Durrgah L.; Maghsoudlou, Panagiotis; Urbani, Luca; Thrasher, Adrian J.

2018-01-01

Clinical success of in utero transplantation (IUT) using allogeneic hematopoietic stem cells (HSCs) has been limited to fetuses that lack an immune response to allogeneic cells due to severe immunological defects, and where transplanted genetically normal cells have a proliferative or survival advantage. Amniotic fluid (AF) is an autologous source of stem cells with hematopoietic potential that could be used to treat congenital blood disorders. We compared the ability of congenic and allogeneic mouse AF stem cells (AFSC) to engraft the hematopoietic system of time-mated C57BL/6J mice (E13.5). At 4 and 16 weeks of age, multilineage donor engraftment was higher in congenic versus allogeneic animals. In vitro mixed lymphocyte reaction confirmed an immune response in the allogeneic group with higher CD4 and CD8 cell counts and increased proliferation of stimulated lymphocytes. IUT with congenic cells resulted in 100% of donor animals having chimerism of around 8% and successful hematopoietic long-term engraftment in immune-competent mice when compared with IUT with allogeneic cells. AFSCs may be useful for autologous cell/gene therapy approaches in fetuses diagnosed with congenital hematopoietic disorders. PMID:29482456

Associations between repetitive questioning, resistance to change, temper outbursts and anxiety in Prader-Willi and Fragile-X syndromes.

PubMed

Woodcock, K; Oliver, C; Humphreys, G

2009-03-01

The behavioural phenotypes of Prader-Willi (PWS) and Fragile-X (FraX) syndromes both comprise repetitive behaviours with differences between the profiles. In this study we investigated the context and antecedents to the repetitive behaviours and the association with other behavioural phenotypic characteristics in order to generate testable hypotheses regarding the cause of the behaviours. The parents or carers of 46 children with PWS (mean age 14.1 years; 20 girls), and 33 boys with FraX (mean age 13.11 years) were interviewed about their children's repetitive behaviour in a semi-structured format. Children showed negative emotional behaviour (PWS: 87.0%; FraX: 79.4%) and repetitive questions (PWS: 78.3%; FraX: 73.5%) following changes in routine or expectations. Significantly more temper outbursts were reported to follow changes in children with PWS (89.1%) compared with boys with FraX (41.2%) (chi(2) = 20.93; P < 0.001). Anxiety that was frequently associated with repetitive and self-injurious behaviours in boys with FraX, followed changes in significantly more boys with FraX (76.5%) compared with children with PWS (6.5%) (chi(2) = 43.19, P < 0.001). On the basis of these reports and existing literature, we hypothesise that decreases in predictability are aversive to children with PWS and FraX. We also hypothesise that these children have a propensity to show a syndrome-related pattern of behaviour (temper outbursts in PWS and displays of anxiety in FraX) when an event in the environment has this aversive property. We hypothesise that questions may be reinforcing to children in their own right by increasing the predictability of the environment. We outline how a specific cognitive deficit in the endophenotypes associated with both PWS and FraX could be investigated as a potential explanation for the hypothesised aversive properties of decreased predictability.

Services Specialist Career Ladder AFSC 611X0.

DTIC Science & Technology

1986-06-01

REQUEST) 52 INSPECT PERSONNEL FOR COMPLIANCE WITH MILITARY STANDARDS 52 INTERPRET POLICIES OR DIRECTIVES FOR SUBORDINATES 52 MAKE ENTRIES ON AF FORMS 1297...67 DETERMINE SUPPLIES REQUIREMENTS 61 INTERPRET POLICIES OR DIRECTIVES FOR SUBORDINATES 61 SUPERVISE MILITARY PERSONNEL IN AFSCs OTHER THAN 611XO 61...m I w c a- ’- a -- I co 0tz ( I co aI o C)-0 a c Ia)aP"o%. B3 C> LO LO qr cnCD C") C"j LA) (1) t.0C) 0 co CD Lo~ -I c)U- LA CY r) zr U’)L r~- r 𔃺 LO

5 CFR 6001.104 - Prohibited financial interests.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 6001.104 Administrative Personnel DEPARTMENT OF TRANSPORTATION SUPPLEMENTAL STANDARDS OF ETHICAL... company subject to FRA regulation. (2) No FRA employee appointed after December 1991 shall hold reemployment rights with a railroad company subject to FRA regulation after his or her first year of employment...

76 FR 2441 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-13

... mandated by Federal regulations. In summary, FRA reasons that comments received will advance three... assigned OMB control number in any correspondence submitted. FRA will summarize comments received in... activities are necessary for FRA to properly execute its functions, including whether the activities will...

Mind the gap: the distributional effects of raising the early eligibility age and full retirement age.

PubMed

Olsen, Anya

2012-01-01

Policymakers have proposed increases to the early eligibility age (EEA) and/or full retirement age (FRA) to address increasing life expectancy and Social Security solvency issues. This analysis uses the Social Security Administration's Modeling Income in the Near Term, version 6 (MINT6) model to compare three retirement-age increases suggested by the Social Security Advisory Board: increase the gap between the EEA and FRA by raising only the FRA, increase both the EEA and FRA to maintain a 4-year gap between them, and increase both the EEA and FRA to maintain a 5-year gap between them. Although all three options would improve system solvency by similar proportions, their effect on individual beneficiaries in the future would vary. Benefit reductions are greater under the proposals with more months between the EEA and FRA, while the option that maintains a 4-year gap results in benefit increases for some beneficiaries compared with current law.

Sequence specific peptidomimetic molecules inhibitors of a protein-protein interaction at the helix 1 level of c-Myc.

PubMed

Nieddu, Erika; Melchiori, A; Pescarolo, M P; Bagnasco, L; Biasotti, B; Licheri, B; Malacarne, D; Tortolina, L; Castagnino, N; Pasa, S; Cimoli, G; Avignolo, C; Ponassi, R; Balbi, C; Patrone, E; D'arrigo, C; Barboro, P; Vasile, F; Orecchia, P; Carnemolla, B; Damonte, G; Millo, E; Palomba, D; Fassina, G; Mazzei, M; Parodi, S

2005-04-01

Our work is focused in the broad area of strategies and efforts to inhibit protein-protein interactions. The possible strategies in this field are definitely much more varied than in the case of ATP-pocket inhibitors. In our previous work (10), we reported that a retro-inverso (RI) form of Helix1 (H1) of c-Myc, linked to an RI-internalization sequence arising from the third alpha-helix of Antennapedia (Int) was endowed with an antiproliferative and proapoptotic activity toward the cancer cell lines MCF-7 and HCT-116. The activity apparently was dependent upon the presence of the Myc motif. In this work, by ala-scan mapping of the H1 portion of our molecules with D-aa, we found two amino acids necessary for antiproliferative activity: D-Lys in 4 and D-Arg in 5 (numbers refer to L-forms). In the natural hetero-dimer, these two side chains project to the outside of the four alpha-helix bundle. Moreover, we were able to obtain three peptides more active than the original lead. They strongly reduced cell proliferation and survival (RI-Int-VV-H1-E2A,S6A,F8A; RI-Int-VV-H1-S6A,F8A,R11A; RI-Int-VV-H1-S6A,F8A,Q13A): after 8 days at 10 muM total cell number was approximately 1% of the number of cells initially seeded. In these more potent molecules, the ablated side chains project to the inside in the corresponding natural four alpha-helix bundle. In the present work, we also investigated the behavior of our molecules at the biochemical level. Using both a circular dichroism (CD) and a fluorescence anisotropy approach, we noted that side chains projecting at the interior of the four alpha-helix bundle are needed for inducing the partial unfolding of Myc-H2, without an opening of the leucine zipper. Side chains projecting at the outside are not required for this biochemical effect. However, antiproliferative activity had the opposite requirements: side chains projecting at the outside of the bundle were essential, and, on the contrary, ablation of one side chain at a time projecting at the inside increased rather than decreased biological activity. We conclude that our active molecules probably interfere at the level of a protein-protein interaction between Myc-Max and a third protein of the transcription complex. Finally, CD and nuclear magnetic resonance (NMR) data, plus dynamic simulations, suggest a prevalent random coil conformation of the H1 portion of our molecules, at least in diluted solutions. The introduction of a kink (substitution with proline in positions 5 or 7) led to an important reduction of biological activity. We have also synthesized a longer peptido-mimetic molecule (RI-Int-H1-S6A,F8A-loop-H2) with the intent of obtaining a wider zone of interaction and a stronger interference at the level of the higher-order structure (enhanceosome). RI-Int-H1-S6A,F8A-loop-H2 was less active rather than more active in respect to RI-Int-VV-H1-S6A,F8A, apparently because it has a clear bent to form a beta-sheet (CD and NMR data).

49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

Code of Federal Regulations, 2010 CFR

2010-10-01

... new regulations, persistent safety concerns, emerging technology, and compliance issues. Also, FRA... history of compliance, FRA inspectors consider “such other factors as the immediate circumstances make... eliminating the safety hazard; the entity's culpability; the entity's compliance history; the entity's ability...

76 FR 38455 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-30

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Numbers FRA-2003-14565 and FRA-2006-24216] Petition for Waiver of Compliance In accordance with part 211 of Title 49 of the Code... Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad safety...

Culicoides Biting Midges (Diptera: Ceratopogonidae) of Kenya

DTIC Science & Technology

1990-03-01

Culicoides. Two of these viruses cause human disease, including Shuni virus (Nigeria, South Af- rica) and Oropouche virus (Trinidad, Brazil, Co...in the field and for virus iso- lation and transmission studies. Taxonomic History and Group Systematics Khamala & Kettle (1971) gave an account of...the Animal Virus Research Institute, Pirbright. Richard Lane of the British Museum (Natural History), London, assisted with the !nm cd type

Proceedings of the Workshop on Multivariable Control Systems Held at Wright-Patterson AFB, OH, on 3 December 1982.

DTIC Science & Technology

1983-09-01

promising method of af- craft multivariable flight controller design. Like any ne.! design technique, there is still more to learn about the r.~ cd...M4atix - Feedback Gain Ma trix - Fandom ’htrix Z - Number of Outputs L1 - Roll Moment • : ’ - 7oll Moment with Inertia TrML 523 a.. Symbols m - Number of

76 FR 50320 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

... the FRA Administrator, FRA issued revisions to the regulations governing freight power brakes and... regulatory requirements related to power brakes on freight cars as well as the recently added requirements... (ICR) that FRA will submit for clearance by OMB as required under the PRA: Title: Inspection Brake...

78 FR 34151 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2013-0050] Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0050. Applicant: Wisconsin...

78 FR 54952 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad safety regulations contained at 49 CFR Part 232, Brake System Safety Standards for Freight and Other Non- Passenger Trains and Equipment; End-of-Train Devices. FRA assigned the petition Docket Number FRA-2013-0080. In its...

78 FR 47823 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

... Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad safety regulations contained at 49 CFR Part 232, Brake System Safety Standards for Freight and Other Non-Passenger Trains and Equipment; End-of-Train Devices. FRA assigned the petition Docket Number FRA-2013-0069...

The Strawberry Pathogenesis-related 10 (PR-10) Fra a Proteins Control Flavonoid Biosynthesis by Binding to Metabolic Intermediates*

PubMed Central

Casañal, Ana; Zander, Ulrich; Muñoz, Cristina; Dupeux, Florine; Luque, Irene; Botella, Miguel Angel; Schwab, Wilfried; Valpuesta, Victoriano; Marquez, José A.

2013-01-01

Pathogenesis-related 10 (PR-10) proteins are involved in many aspects of plant biology but their molecular function is still unclear. They are related by sequence and structural homology to mammalian lipid transport and plant abscisic acid receptor proteins and are predicted to have cavities for ligand binding. Recently, three new members of the PR-10 family, the Fra a proteins, have been identified in strawberry, where they are required for the activity of the flavonoid biosynthesis pathway, which is essential for the development of color and flavor in fruits. Here, we show that Fra a proteins bind natural flavonoids with different selectivity and affinities in the low μm range. The structural analysis of Fra a 1 E and a Fra a 3-catechin complex indicates that loops L3, L5, and L7 surrounding the ligand-binding cavity show significant flexibility in the apo forms but close over the ligand in the Fra a 3-catechin complex. Our findings provide mechanistic insight on the function of Fra a proteins and suggest that PR-10 proteins, which are widespread in plants, may play a role in the control of secondary metabolic pathways by binding to metabolic intermediates. PMID:24133217

Arrhythmia causes lipid accumulation and reduced glucose uptake.

PubMed

Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2015-01-01

Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

Reproducible automated breast density measure with no ionizing radiation using fat-water decomposition MRI.

PubMed

Ding, Jie; Stopeck, Alison T; Gao, Yi; Marron, Marilyn T; Wertheim, Betsy C; Altbach, Maria I; Galons, Jean-Philippe; Roe, Denise J; Wang, Fang; Maskarinec, Gertraud; Thomson, Cynthia A; Thompson, Patricia A; Huang, Chuan

2018-04-06

Increased breast density is a significant independent risk factor for breast cancer, and recent studies show that this risk is modifiable. Hence, breast density measures sensitive to small changes are desired. Utilizing fat-water decomposition MRI, we propose an automated, reproducible breast density measurement, which is nonionizing and directly comparable to mammographic density (MD). Retrospective study. The study included two sample sets of breast cancer patients enrolled in a clinical trial, for concordance analysis with MD (40 patients) and reproducibility analysis (10 patients). The majority of MRI scans (59 scans) were performed with a 1.5T GE Signa scanner using radial IDEAL-GRASE sequence, while the remaining (seven scans) were performed with a 3T Siemens Skyra using 3D Cartesian 6-echo GRE sequence with a similar fat-water separation technique. After automated breast segmentation, breast density was calculated using FraGW, a new measure developed to reliably reflect the amount of fibroglandular tissue and total water content in the entire breast. Based on its concordance with MD, FraGW was calibrated to MR-based breast density (MRD) to be comparable to MD. A previous breast density measurement, Fra80-the ratio of breast voxels with <80% fat fraction-was also calculated for comparison with FraGW. Pearson correlation was performed between MD (reference standard) and FraGW (and Fra80). Test-retest reproducibility of MRD was evaluated using the difference between test-retest measures (Δ 1-2 ) and intraclass correlation coefficient (ICC). Both FraGW and Fra80 were strongly correlated with MD (Pearson ρ: 0.96 vs. 0.90, both P < 0.0001). MRD converted from FraGW showed higher test-retest reproducibility (Δ 1-2 variation: 1.1% ± 1.2%; ICC: 0.99) compared to MD itself (literature intrareader ICC ≤0.96) and Fra80. The proposed MRD is directly comparable with MD and highly reproducible, which enables the early detection of small breast density changes and treatment response. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

49 CFR 219.206 - FRA access to breath test results.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false FRA access to breath test results. 219.206 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing § 219.206 FRA access to breath test results. Documentation of breath test results must be made available...

49 CFR 219.206 - FRA access to breath test results.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false FRA access to breath test results. 219.206 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing § 219.206 FRA access to breath test results. Documentation of breath test results must be made available...

49 CFR 219.206 - FRA access to breath test results.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false FRA access to breath test results. 219.206 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing § 219.206 FRA access to breath test results. Documentation of breath test results must be made available...

49 CFR 219.206 - FRA access to breath test results.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false FRA access to breath test results. 219.206 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing § 219.206 FRA access to breath test results. Documentation of breath test results must be made available...

49 CFR 219.206 - FRA access to breath test results.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false FRA access to breath test results. 219.206 Section... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Post-Accident Toxicological Testing § 219.206 FRA access to breath test results. Documentation of breath test results must be made available...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

49 CFR 219.602 - FRA Administrator's determination of random drug testing rate.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Random Alcohol and Drug Testing Programs § 219.602 FRA Administrator's determination of random drug... percentage rate for random drug testing must be 50 percent of covered employees. (b) The FRA Administrator's decision to increase or decrease the minimum annual percentage rate for random drug testing is based on the...

78 FR 14876 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... Central Texas Railway (TC) has petitioned the Federal Railroad Administration (FRA) for a waiver of...). FRA assigned the petition Docket Number FRA-2013-0012. In its petition, TC seeks relief from 49 U.S.C... on-duty period for 6 consecutive days. Specifically, TC seeks a waiver to allow a train employee to...

49 CFR 228.407 - Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Analysis of work schedules; submissions; FRA... Employees Engaged in Commuter or Intercity Rail Passenger Transportation § 228.407 Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue mitigation plans. (a) Analysis of...

Aberrant Neural Function during Emotion Attribution in Female Subjects with Fragile X Syndrome

ERIC Educational Resources Information Center

Hagan, Cindy C.; Hoeft, Fumiko; Mackey, Allyson; Mobbs, Dean; Reiss, Allan L.

2008-01-01

The neurobiological systems which underlie emotion attribution among female patients with Fragile X (FraX) syndrome are examined. Results show that the emotion circuit which regulates responses to facial stimuli is potentially disrupted among female subjects with FraX syndrome. Anterior cingulate cortex activity in female subjects with FraX…

49 CFR 225.21 - Forms.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Injury and Illness Summary. Form FRA F 6180.55 must be filed each month, even though no reportable... miles, yard switching train miles, and other train miles run during the month. (c) Form FRA 6180.55a—Railroad Injury and Illness (Continuation Sheet). Form FRA 6180.55a shall be used to report all reportable...

Chapter 2: The forestry reclamation approach

Treesearch

Jim Burger; Don Graves; Patrick Angel; Vic Davis; Carl Zipper

2017-01-01

The Forestry Reclamation Approach (FRA) is a method for reclaiming coal-mined land to forest under the federal Surface Mining Control and Reclamation Act of 1977 (SMCRA). The FRA is based on knowledge gained from both scientific research and experience (Fig. 2-1). The FRA can achieve cost-effective regulatory compliance for mine operators while creating productive...

Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

PubMed Central

Akin, Orkun; Zipursky, S Lawrence

2016-01-01

Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it. Thus, despite the graded ligand distribution along the guidance path, Net-Fra is not used for chemoattraction. Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidance in vivo, thereby eroding the distinction between them. DOI: http://dx.doi.org/10.7554/eLife.20762.001 PMID:27743477

Importin-β Directly Regulates the Motor Activity and Turnover of a Kinesin-4.

PubMed

Ganguly, Anindya; DeMott, Logan; Zhu, Chuanmei; McClosky, Daniel D; Anderson, Charles T; Dixit, Ram

2018-03-12

Spatiotemporal regulation of kinesins is essential for microtubule-dependent intracellular transport. In plants, cell wall deposition depends on the FRA1 kinesin, whose abundance and motility are tightly controlled to match cellular growth rate. Here, we show that an importin-β, IMB4, regulates FRA1 activity in a developmental manner. IMB4 physically interacts with a PY motif in the FRA1 motor domain and inhibits its motility by preventing microtubule binding, while also protecting FRA1 against proteasome-mediated degradation, thus providing a mechanism to couple the motility and stability of FRA1. This regulatory mechanism is likely to be broadly applicable, based on the conservation of the PY motif in the motor domains of plant and animal kinesins and the direct interaction of multiple plant kinesins with IMB4. Together, our data establish IMB4 as a multi-functional regulator of FRA1 and reveal a mechanism for how plants control the magnitude of cargo transport needed for cell wall assembly. Copyright © 2018 Elsevier Inc. All rights reserved.

AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia.

PubMed

Zhou, Fengbiao; Liu, Yi; Rohde, Christian; Pauli, Cornelius; Gerloff, Dennis; Köhn, Marcel; Misiak, Danny; Bäumer, Nicole; Cui, Chunhong; Göllner, Stefanie; Oellerich, Thomas; Serve, Hubert; Garcia-Cuellar, Maria-Paz; Slany, Robert; Maciejewski, Jaroslaw P; Przychodzen, Bartlomiej; Seliger, Barbara; Klein, Hans-Ulrich; Bartenhagen, Christoph; Berdel, Wolfgang E; Dugas, Martin; Taketo, Makoto Mark; Farouq, Daneyal; Schwartz, Schraga; Regev, Aviv; Hébert, Josée; Sauvageau, Guy; Pabst, Caroline; Hüttelmaier, Stefan; Müller-Tidow, Carsten

2017-07-01

Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential. Genomic deletion of either C/D box snoRNA SNORD14D or SNORD35A suppressed clonogenic potential of leukaemia cells in vitro and delayed leukaemogenesis in vivo. We further showed that AML1-ETO9a, MYC and MLL-AF9 all enhanced snoRNA formation. Expression levels of C/D box snoRNAs in AML patients correlated closely with in vivo frequency of leukaemic stem cells. Collectively, these findings indicate that induction of C/D box snoRNA/RNP function constitutes an important pathway in leukaemogenesis.

Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1

PubMed Central

Eferl, Robert; Hasselblatt, Peter; Rath, Martina; Popper, Helmut; Zenz, Rainer; Komnenovic, Vukoslav; Idarraga, Maria-Helena; Kenner, Lukas; Wagner, Erwin F.

2008-01-01

Studies using genetically modified mice have revealed fundamental functions of the transcription factor Fos/AP-1 in bone biology, inflammation, and cancer. However, the biological role of the Fos-related protein Fra-2 is not well defined in vivo. Here we report an unexpected profibrogenic function of Fra-2 in transgenic mice, in which ectopic expression of Fra-2 in various organs resulted in generalized fibrosis with predominant manifestation in the lung. The pulmonary phenotype was characterized by vascular remodeling and obliteration of pulmonary arteries, which coincided with expression of osteopontin, an AP-1 target gene involved in vascular remodeling and fibrogenesis. These alterations were followed by inflammation; release of profibrogenic factors, such as IL-4, insulin-like growth factor 1, and CXCL5; progressive fibrosis; and premature mortality. Genetic experiments and bone marrow reconstitutions suggested that fibrosis developed independently of B and T cells and was not mediated by autoimmunity despite the marked inflammation observed in transgenic lungs. Importantly, strong expression of Fra-2 was also observed in human samples of idiopathic and autoimmune-mediated pulmonary fibrosis. These findings indicate that Fra-2 expression is sufficient to cause pulmonary fibrosis in mice, possibly by linking vascular remodeling and fibrogenesis, and suggest that Fra-2 has to be considered a contributing pathogenic factor of pulmonary fibrosis in humans. PMID:18641127

49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to Part 215—FRA Freight Car Standards Defect Code The following defect code has been established for use...

75 FR 59322 - Notice of Availability of Answers to Frequently Asked Questions Regarding Buy America & FRA's...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... Asked Questions can be found on FRA's Web site at http://www.fra.dot.gov/Pages/11.shtml . DATES: Written... electronic site at http://www.regulations.gov . Commenters should follow the instructions below for mailed and hand-delivered comments. (1) Web Site: http://www.regulations.gov . Follow the instructions for...

76 FR 27170 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-10

... Discontinuance or Modification of a Railroad Signal System [Docket Number FRA-2010-0163] In accordance with part... of a signal system. FRA assigned the petition Docket Number FRA-2010-0163. Applicants: Mr. Joseph S. Ivanyo, Chief Engineer, Communications and Signals, CSX Transportation, Inc., 500 Water Street--SC J-350...

76 FR 11992 - Systems for Telephonic Notification of Unsafe Conditions at Highway-Rail and Pathway Grade Crossings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... 3, 2011, one will be scheduled, and FRA will publish a supplemental notice in the Federal Register..., ``Emergency Notification of Grade Crossing Problems,'' of Public Law 103-440, FRA published a report to... for States and Railroads, published August 2007, which can be found at-- http://www.fra.dot.gov...

AFLCMC Cd and Cr Replacement/Elimination Strategy

DTIC Science & Technology

2014-11-18

Dominant Air Power: Design For Tomorrow…Deliver Today Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the...REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Product...Airworthiness Process for Deploying New or Substitute Materials, Processes, and Product Forms 2 Abatement Costs • In Nov 2012, SECAF directed the AF find

Infrared and EPR Spectroscopic Studies of 2-C 2H 2F and 1-C 2H 2F Radicals Isolated in Solid Argon

NASA Astrophysics Data System (ADS)

Goldschleger, I. U.; Akimov, A. V.; Misochko, E. Ya.; Wight, C. A.

2001-02-01

2-fluorovinyl radicals were generated in solid argon by solid-state chemical reactions of mobile F atoms with acetylene and its deuterated analogues. Highly resolved EPR spectra of the stabilized radicals CHF•CH, CDF•CD, CHF•CD, and CDF•CH were obtained for the first time. The observed spectra were assigned to cis-2-fluorovinyl radical based on excellent agreement between the measured (aF = 6.50, aβH = 3.86, aαH = 0.25 mT) hyperfine constants and those calculated using density functional (B3LYP) theory. Analogous experiments carried out using infrared spectroscopy yielded a complete assignment of the vibrational frequencies. An unusual reversible photochemical conversion is observed in which cis-2-fluorovinyl radicals can be partially converted to 1-fluorovinyl radicals by pulsed laser photolysis at 532 nm. Photolysis at 355 nm converts 1-fluorovinyl back to cis-2-fluorovinyl. High-resolution EPR and infrared spectra of 1-fluorovinyl were obtained for the first time. The measured hyperfine constants (aF = 13.71, aH1 = 4.21, aH2 = 1.16 mT) are in good agreement with calculated values.

Synthesis of novel quinoline-based 4,5-dihydro-1H-pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents.

PubMed

Ramírez-Prada, Jonathan; Robledo, Sara M; Vélez, Iván D; Crespo, María Del Pilar; Quiroga, Jairo; Abonia, Rodrigo; Montoya, Alba; Svetaz, Laura; Zacchino, Susana; Insuasty, Braulio

2017-05-05

A new series of N-substituted 2-pyrazolines 9a-f, 10a-f, 11a-f, 12a-f and 13a-f were obtained from the cyclocondensation reaction of [(7-chloroquinolin-4-yl)amino]chalcones 8a-f with hydrazine hydrate and its derivatives. Fourteen of the synthesized compounds including the starting chalcones were selected by US National Cancer Institute (NCI) for testing their anticancer activity against 60 different human cancer cell lines, with the most important GI 50 values ranging from 0.28 to 11.7 μM (0.13-6.05 μg/mL) and LC 50 values ranging from 2.6 to > 100 μM (1.2 to > 51.7 μg/mL), for chalcones 8a,d and pyrazolines 10c,d. All compounds were assessed for antibacterial activity against wild type and multidrug resistant gram negative and gram positive bacteria, with MIC values ranging from 31.25 to 500 μg/mL. Additionally, the novel compounds were tested for antifungal and antiparasitic properties. Although these compounds showed mild activity against Candida albicans, chalcones 8a and 8e showed high activity against Cryptococcus neoformans with MIC 50  = 7.8 μg/mL. For anti-Plasmodium falciparum activity the 2-pyrazoline 11b was the most active with EC 50  = 5.54 μg/mL. Regarding the activity against Trypanosoma cruzi, compound 10a was highly active with EC 50  = 0.70 μg/mL. Chalcone 8a had good activity against Leishmania panamensis amastigotes with EC 50  = 0.79 μg/mL. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of full S1 gene sequencing of classical and variant infectious bronchitis viruses extracted from allantoic fluid and FTA cards.

PubMed

Manswr, Basim; Ball, Christopher; Forrester, Anne; Chantrey, Julian; Ganapathy, Kannan

2018-08-01

Sequence variability in the S1 gene determines the genotype of infectious bronchitis virus (IBV) strains. A single RT-PCR assay was developed to amplify and sequence the full S1 gene for six classical and variant IBVs (M41, D274, 793B, IS/885/00, IS/1494/06 and Q1) enriched in allantoic fluid (AF) or the same AF inoculated onto Flinders Technology Association (FTA) cards. Representative strains from each genotype were grown in specific-pathogen-free eggs and RNA was extracted from AF. Full S1 gene amplification was achieved using primer A and primer 22.51. Products were sequenced using primers A, 1050+, 1380+ and SX3+ to obtain short sequences covering the full gene. Following serial dilutions of AF, detection limits of the partial assay were higher than those of the full S1 gene. Partial S1 sequences exhibited higher-than-average nucleotide similarity percentages (79%; 352 bp) compared to full S1 sequences (77%; 1756 bp), suggesting that full S1 analysis allows greater strain differentiation. For IBV detection from AF-inoculated FTA cards, four serotypes were incubated for up to 21 days at three temperatures, 4°C, room temperature (approximately 24°C) and 40°C. RNA was extracted and tested with partial and full S1 protocols. Through partial sequencing, all IBVs were successfully detected at all sampling points and storage temperatures. In contrast, using full S1 sequencing it was not possible to amplify the gene beyond 14 days or when stored at 40°C. Data presented show that for full S1 sequencing, a substantial amount of RNA is needed. Field samples collected onto FTA cards are unlikely to yield such quantity or quality. AF: allantoic fluid; CD50: ciliostatic dose 50; FTA: Flinders Technology Association; IB: infectious bronchitis; IBV: infectious bronchitis virus.

The F8H Glycosyltransferase is a Functional Paralog of FRA8 Involved in Glucuronoxylan Biosynthesis in Arabidopsis

EPA Science Inventory

The FRAGILE FIBER8 gene was previously shown to be required for the biosynthesis of the reducing end tetrasaccharide sequence of glucuronoxylan (GX) in Arabidopsis thaliana. Here, we demonstrate that F8H, a close homolog of FRA8, is a functional ortholog of FRA8 involved in GX bi...

75 FR 75448 - Revised Proposal for Revisions to the Schedules of Civil Penalties for a Violation of a Federal...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-03

... the Schedules of Civil Penalties for a Violation of a Federal Railroad Safety Law or Federal Railroad... September 21, 2010. The proposal, if adopted, would amend, line by line, FRA's schedules of civil penalties... . SUPPLEMENTARY INFORMATION: FRA's proposal to amend, line by line, FRA's schedules of civil penalties as well as...

Mice with a fra-1 knock-in into the c-fos locus show impaired spatial but regular contextual learning and normal LTP.

PubMed

Gass, Peter; Fleischmann, Alexander; Hvalby, Oivind; Jensen, Vidar; Zacher, Christiane; Strekalova, Tatyana; Kvello, Ane; Wagner, Erwin F; Sprengel, Rolf

2004-11-04

The immediate early gene c-fos is part of the AP-1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c-Fos in the brain show impairments in spatial reference and contextual learning, and also exhibit a reduced long-term potentiation of synaptic transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to determine whether other members of the c-fos gene family can substitute for the functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and contextual learning in a Pavlovian fear conditioning task were similar to wild-type littermates, indicating that Fra-1 expression restored the impairments caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning deficits in a reference memory task of the Morris watermaze were also present in c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are involved in LTP, contextual learning, and spatial reference memory formation.

Genome-wide detection of natural selection in African Americans pre- and post-admixture

PubMed Central

Jin, Wenfei; Xu, Shuhua; Wang, Haifeng; Yu, Yongguo; Shen, Yiping; Wu, Bailin; Jin, Li

2012-01-01

It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre- and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre- and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs. PMID:22128132

Telomere Fragment Induced Amnion Cell Senescence: A Contributor to Parturition?

PubMed Central

Polettini, Jossimara; Behnia, Faranak; Taylor, Brandie D.; Saade, George R.; Taylor, Robert N.; Menon, Ramkumar

2015-01-01

Oxidative stress (OS)-induced senescence of the amniochorion has been associated with parturition at term. We investigated whether telomere fragments shed into the amniotic fluid (AF) correlated with labor status and tested if exogenous telomere fragments (T-oligos) could induce human and murine amnion cell senescence. In a cross-sectional clinical study, AF telomere fragment concentrations quantitated by a validated real-time PCR assay were higher in women in labor at term compared to those not in labor. In vitro treatment of primary human amnion epithelial cells with 40 μM T-oligos ([TTAGGG]2) that mimic telomere fragments, activated p38MAPK, produced senescence-associated (SA) β-gal staining and increased interleukin (IL)-6 and IL-8 production compared to cells treated with complementary DNA sequences (Cont-oligos, [AATCCC]2). T-oligos injected into the uteri of pregnant CD1 mice on day 14 of gestation, led to increased p38MAPK, SA-β-gal (SA β-gal) staining in murine amniotic sacs and higher AF IL-8 levels on day 18, compared to saline treated controls. In summary, term labor AF samples had higher telomere fragments than term not in labor AF. In vitro and in situ telomere fragments increased human and murine amnion p38MAPK, senescence and inflammatory cytokines. We propose that telomere fragments released from senescent fetal cells are indicative of fetal cell aging. Based on our data, these telomere fragments cause oxidative stress associated damages to the term amniotic sac and force them to release other DAMPS, which, in turn, provide a sterile immune response that may be one of the many inflammatory signals required to initiate parturition at term. PMID:26397719

β-Cyclodextrin-dextran polymers for the solubilization of poorly soluble drugs.

PubMed

di Cagno, Massimiliano; Terndrup Nielsen, Thorbjørn; Lambertsen Larsen, Kim; Kuntsche, Judith; Bauer-Brandl, Annette

2014-07-01

The aim of this study was to assess the potential of novel β-cyclodextrin (βCD)-dextran polymers for drug delivery. The size distribution of βCD-dextrans (for eventual parenteral administration), the influence of the dextran backbones on the stability of the βCD/drug complex, the solubilization efficiency of poorly soluble drugs and drug release properties were investigated. Size analysis of different βCD-dextrans was measured by size exclusion chromatography (SEC) and asymmetrical flow field-flow fractionation (AF4). Stability of drug/βCD-dextrans was assessed by isothermal titration calorimetry (ITC) and molar enthalpies of complexation and equilibrium constants compared to some commercially available βCD derivatives. For evaluation of the solubilization efficiency, phase-solubility diagrams were made employing hydrocortisone (HC) as a model of poorly soluble drugs, whereas reverse dialysis was used to detect potential drug supersaturation (increased molecularly dissolved drug concentration) as well as controlled release effects. Results indicate that all investigated βCD-polymers are of appropriate sizes for parenteral administration. Thermodynamic results demonstrate that the presence of the dextran backbone structure does not affect the stability of the βCD/drug complex, compared to native βCD and commercially available derivatives. Solubility studies evidence higher solubilizing abilities of these new polymers in comparison to commercially available βCDs, but no supersaturation states were induced. Moreover, drug release studies evidenced that diffusion of HC was influenced by the solubilization induced by the βCD-derivatives. Copyright © 2014 Elsevier B.V. All rights reserved.

Paving the way to a full chip gate level double patterning application

NASA Astrophysics Data System (ADS)

Haffner, Henning; Meiring, Jason; Baum, Zachary; Halle, Scott

2007-10-01

Double patterning lithography processes can offer significant yield enhancement for challenging circuit designs. Many decomposition (i.e. the process of dividing the layout design into first and second exposures) techniques are possible, but the focus of this paper is on the use of a secondary "cut" mask to trim away extraneous features left from the first exposure. This approach has the advantage that each exposure only needs to support a subset of critical features (e.g. dense lines with the first exposure, isolated spaces with the second one). The extraneous features ("printing assist features" or PrAFs) are designed to support the process window of critical features much like the role of the subresolution assist features (SRAFs) in conventional processes. However, the printing nature of PrAFs leads to many more design options, and hence a greater process and decomposition parameter exploration space, than are available for SRAFs. A decomposition scheme using PRAFs was developed for a gate level process. A critical driver of the work was to deliver improved across-chip linewidth variation (ACLV) performance versus an optimized single exposure process while providing support for a larger range of critical features. A variety of PRAF techniques were investigated by simulation, with a PrAF scheme similar to standard SRAF rules being chosen as the optimal solution [1]. This paper discusses aspects of the code development for an automated PrAF generation and placement scheme and the subsequent decomposition of a layout into two mask levels. While PrAF placement and decomposition is straightforward for layouts with pitch and orientation restrictions, it becomes rather complex for unrestricted layout styles. Because this higher complexity yields more irregularly shaped PrAFs, mask making becomes another critical driver of the optimum placement and clean-up strategies. Examples are given of how those challenges are met or can be successfully circumvented. During subsequent decomposition of the PrAF-enhanced layout into two independent mask levels, various geometric decomposition parameters have to be considered. As an example, the removal of PrAFs has to be guaranteed by a minimum required overlap of the cut mask opening past any PrAF edge. It is discussed that process assumptions such as CD tolerances and overlay as well as inter-level relationship ground rules need to be considered to successfully optimize the final decomposition scheme. Furthermore, simulation and experimental results regarding not only ACLV but also across-device linewidth variation (ADLV) are analyzed.

Chapter 9: Planting hardwood tree seedlings on reclaimed mine land in the Appalachian region

Treesearch

V. Davis; J. Franklin; C. Zipper; P. Angel

2017-01-01

The Forestry Reclamation Approach (FRA) is a method of reclaiming surface coal mines to forested postmining land use (Chapter 2, this volume). "Use proper tree planting techniques" is Step 5 of the FRA; when used with the other FRA steps, proper tree planting can help to ensure successful reforestation. Proper care and planting of tree seedlings is essential...

Apollo 14 - Nature and origin of rock types in soil from the Fra Mauro formation.

NASA Technical Reports Server (NTRS)

Aitken, F. K.; Anderson, D. H.; Bass, M. N.; Brown, R. W.; Butler, P., Jr.; Heiken, G.; Jakes, P.; Reid, A. M.; Ridley, W. I.; Takeda, H.

1971-01-01

Compositions of glasses in the Apollo 14 soil correspond to four types of Fra Mauro basalts, to mare basalts and soils, and, in minor amounts, to gabbroic anorthosite and potash granite. The Fra Mauro basalts can be related by simple low pressure crystal-liquid fractionation that implies a parent composition like that of Apollo 14 sample 14310.

49 CFR 229.207 - New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive...

Code of Federal Regulations, 2010 CFR

2010-10-01

... requirements of § 229.205 for the type of locomotive design or provides at least an equivalent level of safety... least an equivalent level of safety. Types of data and analysis to be considered are described in § 229.211(c)(1). (d) Petitions for FRA approval of non-substantive changes to the existing FRA-approved...

Anthropometric and craniofacial patterns in mentally retarded males with emphasis on the fragile X syndrome.

PubMed

Butler, M G; Pratesi, R; Watson, M S; Breg, W R; Singh, D N

1993-09-01

Anthropometric and craniofacial profile patterns indicating the percent difference from the overall mean were developed on 34 physical parameters with 31 white, mentally retarded males (23 adults and 8 children) with the fra(X) syndrome matched for age with 31 white, mentally retarded males without a known cause of their retardation. The fra(X) syndrome males consistently showed larger dimensions for all anthropometric variables, with significant differences for height, sitting height, arm span, hand length, middle finger length, hand breadth, foot length, foot breadth, and testicular volume. A craniofacial pattern did emerge between the two groups of mentally retarded males, but with overlap of several variables. Significant differences were noted for head circumference, head breadth, lower face height, bizygomatic diameter, inner canthal distance, ear length and ear width, with the fra(X) syndrome males having larger head dimensions (head circumference, head breadth, head length, face height and lower face height), but smaller measurements for minimal frontal diameter, bizygomatic diameter, bigonial diameter, and inner canthal distance. Several significant correlations were found with the variables for both mentally retarded males with and without the fra(X) syndrome. In a combined anthropometric and craniofacial profile of 19 variables comparing 26 white fra(X) syndrome males (13 with high expression (> 30%) and 13 with low expression (< 30%), but matched for age), a relatively flat profile was observed with no significant differences for any of the variables. Generally, fra(X) syndrome males with increased fragile X chromosome expression have larger amplifications of the CGG trinucleotide repeat of the FMR-1 gene. No physical differences were detectable in our study between fra(X) males with high expression and apparently larger amplifications of the CGG trinucleotide repeats compared with those patients with low expression. Our research illustrates the use of anthropometry in identifying differences between mentally retarded males with or without the fra(X) syndrome and offers a comprehensive approach for screening males for the fra(X) syndrome and selecting those individuals for cytogenetic and/or molecular genetic testing.

Anthropometric and craniofacial patterns in mentally retarded males with emphasis on the fragile X syndrome

PubMed Central

Butler, Merlin G.; Pratesi, Riccardo; Watson, Michael S.; Breg, W. Roy; Singh, Dharmdeo N.

2017-01-01

Anthropometric and craniofacial profile patterns indicating the percent difference from the overall mean were developed on 34 physical parameters with 31 white, mentally retarded males (23 adults and 8 children) with the fra(X) syndrome matched for age with 31 white, mentally retarded males without a known cause of their retardation. The fra(X) syndrome males consistently showed larger dimensions for all anthropometric variables, with significant differences for height, sitting height, arm span, hand length, middle finger length, hand breadth, foot length, foot breadth, and testicular volume. A craniofacial pattern did emerge between the two groups of mentally retarded males, but with overlap of several variables. Significant differences were noted for head circumference, head breadth, lower face height, bizygomatic diameter, inner canthal distance, ear length and ear width, with the fra(X) syndrome males having larger head dimensions (head circumference, head breadth, head length, face height and lower face height), but smaller measurements for minimal frontal diameter, bizygomatic diameter, bigonial diameter, and inner canthal distance. Several significant correlations were found with the variables for both mentally retarded males with and without the fra(X) syndrome. In a combined anthropometric and craniofacial profile of 19 variables comparing 26 white fra(X) syndrome males (13 with high expression (>30%) and 13 with low expression (< 30%), but matched for age), a relatively flat profile was observed with no significant differences for any of the variables. Generally, fra(X) syndrome males with increased fragile X chromosome expression have larger amplifications of the CGG trinucleotide repeat of the FMR-1 gene. No physical differences were detectable in our study between fra(X) males with high expression and apparently larger amplifications of the CGG trinucleotide repeats compared with those patients with low expression. Our research illustrates the use of anthropometry in identifying differences between mentally retarded males with or without the fra(X) syndrome and offers a comprehensive approach for screening males for the fra(X) syndrome and selecting those individuals for cytogenetic and/or molecular genetic testing. PMID:8275570

[German version of the math anxiety questionnaire (FRA) for 6- to 9-year-old children].

PubMed

Krinzinger, Helga; Kaufmann, Liane; Dowker, Ann; Thomas, Gemma; Graf, Martina; Nuerk, Hans-Christoph; Willmes, Klaus

2007-09-01

Is the FRA a reliable and valid instrument? Are there any gender differences concerning math anxiety? Are there any developmental changes in this regard in the course of the early grades? Together with the dyscalculia test TEDI-MATH, the FRA was presented to a total of 450 children from the first to the third grade of primary school (at least 40 girls and 40 boys per semester). The total scale has an internal consistency (Cronbach's alpha) between 0.83 and 0.91. Correlations between arithmetic skills and the FRA scales were mostly significant. The significantly higher negative scores for girls were taken into account by providing standard scores corrected for gender. No systematic developmental changes could be observed. The FRA is the first German math anxiety questionnaire for primary school children. High reliability, standard scores corrected for gender, and economic handling make it an instrument well suited for use in clinical settings (e.g., dyscalculia diagnostics and intervention).

Solution structure of the strawberry allergen Fra a 1

PubMed Central

Seutter von Loetzen, Christian; Schweimer, Kristian; Schwab, Wilfried; Rösch, Paul; Hartl-Spiegelhauer, Olivia

2012-01-01

The PR10 family protein Fra a 1E from strawberry (Fragaria x ananassa) is down-regulated in white strawberry mutants, and transient RNAi (RNA interference)-mediated silencing experiments confirmed that Fra a 1 is involved in fruit pigment synthesis. In the present study, we determined the solution structure of Fra a 1E. The protein fold is identical with that of other members of the PR10 protein family and consists of a seven-stranded antiparallel β-sheet, two short V-shaped α-helices and a long C-terminal α-helix that encompass a hydrophobic pocket. Whereas Fra a 1E contains the glycine-rich loop that is highly conserved throughout the protein family, the volume of the hydrophobic pocket and the size of its entrance are much larger than expected. The three-dimensional structure may shed some light on its physiological function and may help to further understand the role of PR10 proteins in plants. PMID:22913709

FRaC: a feature-modeling approach for semi-supervised and unsupervised anomaly detection.

PubMed

Noto, Keith; Brodley, Carla; Slonim, Donna

2012-01-01

Anomaly detection involves identifying rare data instances (anomalies) that come from a different class or distribution than the majority (which are simply called "normal" instances). Given a training set of only normal data, the semi-supervised anomaly detection task is to identify anomalies in the future. Good solutions to this task have applications in fraud and intrusion detection. The unsupervised anomaly detection task is different: Given unlabeled, mostly-normal data, identify the anomalies among them. Many real-world machine learning tasks, including many fraud and intrusion detection tasks, are unsupervised because it is impractical (or impossible) to verify all of the training data. We recently presented FRaC, a new approach for semi-supervised anomaly detection. FRaC is based on using normal instances to build an ensemble of feature models, and then identifying instances that disagree with those models as anomalous. In this paper, we investigate the behavior of FRaC experimentally and explain why FRaC is so successful. We also show that FRaC is a superior approach for the unsupervised as well as the semi-supervised anomaly detection task, compared to well-known state-of-the-art anomaly detection methods, LOF and one-class support vector machines, and to an existing feature-modeling approach.

FRaC: a feature-modeling approach for semi-supervised and unsupervised anomaly detection

PubMed Central

Brodley, Carla; Slonim, Donna

2011-01-01

Anomaly detection involves identifying rare data instances (anomalies) that come from a different class or distribution than the majority (which are simply called “normal” instances). Given a training set of only normal data, the semi-supervised anomaly detection task is to identify anomalies in the future. Good solutions to this task have applications in fraud and intrusion detection. The unsupervised anomaly detection task is different: Given unlabeled, mostly-normal data, identify the anomalies among them. Many real-world machine learning tasks, including many fraud and intrusion detection tasks, are unsupervised because it is impractical (or impossible) to verify all of the training data. We recently presented FRaC, a new approach for semi-supervised anomaly detection. FRaC is based on using normal instances to build an ensemble of feature models, and then identifying instances that disagree with those models as anomalous. In this paper, we investigate the behavior of FRaC experimentally and explain why FRaC is so successful. We also show that FRaC is a superior approach for the unsupervised as well as the semi-supervised anomaly detection task, compared to well-known state-of-the-art anomaly detection methods, LOF and one-class support vector machines, and to an existing feature-modeling approach. PMID:22639542

Metallothionein turnover in mammalian cell lines: implications in drug resistance

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

Monia, B.P.; Butt, T.R.; Ecker, D.J.

1986-05-01

Metallothioneins (MT) are low molecular weight, cysteine-rich proteins believed to participate in metal detoxification. A wide variety of cells in culture have been shown to accumulate MT in response to metal administration. These metal-induced increases in MT levels result from an increased rate of MT gene transcription, MT mRNA accumulation, and MT synthesis. Turnover of Cd-, Zn- and Au-induced MT was studied in a Chinese Hamster Ovary (CHO) cell line which was resistant to Cd and the Au-containing drug Auranofin (AF). Cd, Zn and Au were potent inducers of MT mRNA and accumulated approximately equal amounts of mRNA under themore » conditions employed in this study. Pulse-chase studies utilizing (/sup 35/S)cysteine revealed that the half-life of Au-, Zn- and Cd-induced MT was 0.75, 10 and 24 hrs. respectively. The reported differences in the tertiary structure of Au-MT from that of Cd-MT lead us to propose that the differences in half-lives observed reflect differences in subceptibility to intracellular proteolysis, which in turn, may effect the ability of MT to confer resistance to various metals.« less

Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis.

PubMed

Maurer, Britta; Busch, Nicole; Jüngel, Astrid; Pileckyte, Margarita; Gay, Renate E; Michel, Beat A; Schett, Georg; Gay, Steffen; Distler, Jörg; Distler, Oliver

2009-12-08

Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected. Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.

USAF Bioenvironmental Noise Data Handbook. Volume 130. A-7 Aircraft in the AF32A-19 and the AF32A-24 Noise Suppressors, Near and Far-Field Noise.

DTIC Science & Technology

1980-07-01

C2 w C3 0 . . . . 0 0 0 0 1 CO Cl UJI ty . . I. . . . . . . . . . I. . . . . U, Z 91 Is . . . 0 0 0 0 r U z ce tD z us z m z woe z 0 00 CL ti) 0 Z 6...I( x O~ tD .)Z ,ll . . .P .. . . .. . .o 0 z : :• (Y -, 11-4 I •••••• It; rl L-l ulC z co i’Li u 11 1 gr - - - -- -.... .... ....... ..U3U% A, z oc ao...II 𔃻 3 - - 3 - 33 - -a z 0 jAj " 7 nu ~ fu j( ~ : .. \\./ : * a a a32 m 4’ . 4t... U 0 10,0 r,,_ I,. co CD 1,4 Z c a 0 -- -- 64 "*" o :) € go e ° o

REMBASS Commandability. Trade Off Analysis (TOA)/Trade Off Determination (TOD)

DTIC Science & Technology

1977-12-15

3 " 1 0 r-4 V) C-H ) 4-4 4-) 9 4 4- q)$- G C C) P U4J~4 0 4)rz Q1 ’ :;l CZt 4- -4 > E Cd P4r 4 .+ 0. 0 co a) u~f V) UA0 G + ZU) <D +J U) ’-I 4 4-4...i I- . .I I .... . ..... . . .... ... .. . . .. . .... ; = = r ; - *~rj ~*r r P55 - U i- :t4 1 SA" I I-I * I,. " aF " -- UP*5 6...to LC)LO n O L L LnLf LOCL0 3 .L) C’- LuJE4 V)I )L nLIV)tX:X af -VC / "*.-n = CO ccccccca oC . O C,-oCor-.oC CCaOC) tCM W 4WMwC o nU) MWO 4- 4. 4-) 0.-U

[Expression and correlation of Fra-1 and HMGA1 in laryngeal squamous cell carcinoma].

PubMed

Zhang, Y L; Song, X F; Duan, Y J; Zhao, R L

2017-12-07

Objective: To investigate the expressions of Fra -1 and HMGA 1 in laryngeal squamous cell carcinoma and their correlation . Methods: Immunohistochemistry and reverse transcription-polymer chain reaction (RT-PCR) were used to detect the expressions of HMGA 1 and Fra -1 in laryngeal squamous carcinoma tissues in 47 cases and para - carcinoma tissues in 21 cases ( the First Hospital of Shijiazhuang ). The relationship between the gene expressions in carcinoma tissues and clinopathological parameters such as pathological grade, clinical stage, lymph metastasis, age and anatomic site and the relevance of the two gene expressions were analyzed . SPSS 13.0 software was used to analyze the data . Results: The positive expression rates of Fra-1 and HMGA1 proteins in laryngeal squamous cancer tissue were 48.9% and 53.2%, which were respectively higher than the rates of 19.0% for Fra-1 (χ(2)=5.416, P <0.05) and of 23.8% for HMGA1 (χ(2)=5.083, P <0.05) in adjacent tissues. The expression of Fra -1 gene was correlation with pathological grade, clinical stage and lymph metastasis (t values were -1.079, -1.066 and -1.067, all P<0.05), but not with age and anatomic site (t values were -1.068 and -1.054, both P>0.05). The expression of HMGA 1 gene was correlation with pathological grade, clinical stage, lymph metastasis and age (t values were -1.112, -1.065, -1.009 and -1.066, all P<0.05), but not with anatomic site (t=-1.036, P>0.05). The expressions of Fra -1 and HMGA 1 gene were positively correlation (r=0.672, P<0.05). Conclusions: In laryngeal squamous cancer, Fra -1 and HMGA 1 are excessive expression, with a positive correlation between the expressions of both genes .

Fos and FRA protein expression in rat nucleus paragigantocellularis lateralis during different space flight conditions.

PubMed

d'Ascanio, Paola; Centini, Claudia; Pompeiano, Maria; Pompeiano, Ottavio; Balaban, Evan

2002-10-15

The nucleus paragigantocellularis lateralis (LPGi) exerts a prominent excitatory influence over locus coeruleus (LC) neurons, which respond to gravity signals. We investigated whether adult albino rats exposed to different gravitational fields during the NASA Neurolab Mission (STS-90) showed changes in Fos and Fos-related antigen (FRA) protein expression in the LPGi and related cardiovascular, vasomotor, and respiratory areas. Fos and FRA proteins are induced rapidly by external stimuli and return to basal levels within hours (Fos) or days (FRA) after stimulation. Exposure to a light pulse (LP) 1 h prior to sacrifice led to increased Fos expression in subjects maintained for 2 weeks in constant gravity (either at approximately 0 or 1 G). Within 24 h of a gravitational change (launch or landing), the Fos response to LP was abolished. A significant Fos response was also induced by gravitational stimuli during landing, but not during launch. FRA responses to LP showed a mirror image pattern, with significant responses 24 h after launch and landing, but no responses after 2 weeks at approximately 0 or 1 G. There were no direct FRA responses to gravity changes. The juxtafacial and retrofacial parts of the LPGi, which integrate somatosensory/acoustic and autonomic signals, respectively, also showed gravity-related increases in LP-induced FRA expression 24 h after launch and landing. The neighboring nucleus ambiguus (Amb) showed completely different patterns of Fos and FRA expression, demonstrating the anatomical specificity of these results. Immediate early gene expression in the LPGi and related cardiovascular vasomotor and ventral respiratory areas may be directly regulated by excitatory afferents from vestibular gravity receptors. These structures could play an important role in shaping cardiovascular and respiratory function during adaptation to altered gravitational environments encountered during space flight and after return to earth. Copyright 2002 Elsevier Science Inc.

Comparative studies of pharmacokinetics and anticoagulatory effect in rats after oral administration of Frankincense and its processed products.

PubMed

Pan, Ying-Ni; Liang, Xiao-Xu; Niu, Li-Ying; Wang, Yan-Nian; Tong, Xin; Hua, Hui-Ming; Zheng, Jiang; Meng, Dong-Ya; Liu, Xiao-Qiu

2015-08-22

Frankincense (FRA), Ruxiang, is the resin of Boswellia carterii Birdw and Boswellia bhaw-dajiana Birdw which has been used for centuries as formulas to improve the circulation and to relieve pain against carbuncles. Stir-fried Frankincense (SFF) and vinegar processed Frankincense (VPF) are two major processed Frankincense, and the processing procedures reportedly enhance the curative efficacy or reduce the side effects of FRA. This paper describes the comparisons in plasma pharmacokinetic behaviors of 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA) in FRA and its processed products, and their effects on coagulation factors and blood clotting tetrachoric, using an acute cold blood-stasis animal model after oral administration of FRA, SFF, and VPF. For pharmacokinetic study, Sprague-Dawley (SD) rats were randomly divided into three groups, including group FRA, group SFF and group VPF. And the plasma samples were analyzed by HPLC. For study of anticoagulatory effect, SD rats were randomly divided into six groups, including control, acute cold blood-stasis model, Fu-fang-dan-shen tablet- (0.75g/kg), FRA-, SFF-, and VPF-treated (2.7g/kg) groups, respectively. The serum contents of thrombin-antithrombin complex (TAT), D-dimer (D-D), and prostacyclin (PGI2) of each group were measured by ELISA. The values of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were also assessed by hematology analyzer. Significantly increased levels of Cmax, AUC, T1/2, and MRT were found in rats treated with the processed products. In addition, decreased levels of D-D and TAT and increased contents of PGI2 were observed in rats given FRA and its processed products, compared with that of the model group. Moreover, VPF improved anticoagulation more than SFF in the animals. The observed improvement of anticoagulation by processed FRA may result from the increased absorption and bioavailability of triterpenoids. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Copy number and haplotype variation at the VRN-A1 and central FR-A2 loci are associated with frost tolerance in hexaploid wheat.

PubMed

Zhu, Jie; Pearce, Stephen; Burke, Adrienne; See, Deven Robert; Skinner, Daniel Z; Dubcovsky, Jorge; Garland-Campbell, Kimberly

2014-05-01

The interaction between VRN - A1 and FR - A2 largely affect the frost tolerance of hexaploid wheat. Frost tolerance is critical for wheat survival during cold winters. Natural variation for this trait is mainly associated with allelic differences at the VERNALIZATION 1 (VRN1) and FROST RESISTANCE 2 (FR2) loci. VRN1 regulates the transition between vegetative and reproductive stages and FR2, a locus including several tandemly duplicated C-REPEAT BINDING FACTOR (CBF) transcription factors, regulates the expression of Cold-regulated genes. We identified sequence and copy number variation at these two loci among winter and spring wheat varieties and characterized their association with frost tolerance. We identified two FR-A2 haplotypes-'FR-A2-S' and 'FR-A2-T'-distinguished by two insertion/deletions and ten single nucleotide polymorphisms within the CBF-A12 and CBF-A15 genes. Increased copy number of CBF-A14 was frequently associated with the FR-A2-T haplotype and with higher CBF14 transcript levels in response to cold. Factorial ANOVAs revealed significant interactions between VRN1 and FR-A2 for frost tolerance in both winter and spring panels suggesting a crosstalk between vernalization and cold acclimation pathways. The model including these two loci and their interaction explained 32.0 and 20.7 % of the variation in frost tolerance in the winter and spring panels, respectively. The interaction was validated in a winter wheat F 4:5 population segregating for both genes. Increased VRN-A1 copy number was associated with improved frost tolerance among varieties carrying the FR-A2-T allele but not among those carrying the FR-A2-S allele. These results suggest that selection of varieties carrying the FR-A2-T allele and three copies of the recessive vrn-A1 allele would be a good strategy to improve frost tolerance in wheat.

Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further improve human scaffold-based xenograft models.

PubMed

Carretta, Marco; de Boer, Bauke; Jaques, Jenny; Antonelli, Antonella; Horton, Sarah J; Yuan, Huipin; de Bruijn, Joost D; Groen, Richard W J; Vellenga, Edo; Schuringa, Jan Jacob

2017-07-01

Recently, NOD-SCID IL2Rγ -/- (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or Matrigel to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and thrombopoietin (TPO). In vitro, these IL-3- and TPO-producing MSCs were superior in expanding human cord blood (CB) CD34 + hematopoietic stem/progenitor cells. MLL-AF9-transduced CB CD34 + cells could be transformed efficiently along myeloid or lymphoid lineages on IL-3- and TPO-producing MSCs. In vivo, these genetically engineered MSCs maintained their ability to differentiate into bone, adipocytes, and other stromal components. Upon transplantation of MLL-AF9-transduced CB CD34 + cells, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) developed in engineered scaffolds, in which a significantly higher percentage of myeloid clones was observed in the mouse compartments compared with previous models. Engraftment of primary AML, B-cell ALL, and biphenotypic acute leukemia (BAL) patient samples was also evaluated, and all patient samples could engraft efficiently; the myeloid compartment of the BAL samples was better preserved in the human cytokine scaffold model. In conclusion, we show that we can genetically engineer the ectopic human BM microenvironment in a humanized scaffold xenograft model. This approach will be useful for functional study of the importance of niche factors in normal and malignant human hematopoiesis. Copyright © 2017 ISEH - International Society for Experimental Hematology. All rights reserved.

Collision tumor of primary laryngeal mucosal melanoma and invasive squamous cell carcinoma with IL-17A and CD70 gene over-expression.

PubMed

Sirikanjanapong, Sasis; Lanson, Biana; Amin, Milan; Martiniuk, Frank; Kamino, Hideko; Wang, Beverly Y

2010-12-01

The most common primary malignancy of the larynx is the squamous cell carcinoma (SCC). The primary malignant melanoma is quite rare in this location. Less than 60 cases of laryngeal melanomas have been reported to date. To our knowledge, collision primary malignant melanoma and invasive squamous cell carcinoma in the vocal cords has not been reported. We report a 53-year-old male patient who was diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorγT, CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction (Rt-PCR) in this case. Both IL-17A and CD70 genes were detected in this case of collision tumor. The results may define useful biomarkers for early diagnosis of mucosal melanoma and open an immunotherapeutic field for clinical management with the potential benefit from the immunomodulators that enhance both genes.

Geologic implications of the Apollo 14 Fra Mauro breccias and comparison with ejecta from the Ries Crater, Germany

USGS Publications Warehouse

Chao, E.C.T.

1973-01-01

On the basis of petrographic and laboratory and active seismic data for the Fra Mauro breccias, and by comparison with the nature and distribution of the ejecta from the Ries crater, Germany, some tentative conclusions regarding the geologic significance of the Fra Mauro Formation on the moon can be drawn. The Fra Mauro Formation, as a whole, consists of unwcldcd, porous ejecta, slightly less porous than the regolith. It contains hand-specimen and larger size clasts of strongly annealed complex breccias, partly to slightly annealed breccias, basalts, and perhaps spherule-rich breccias. These clasts are embedded in a matrix of porous aggregate dominated by mineral and breccia fragments and probably largely free of undevitrified glass. All strongly annealed hand-specimen-size breccias are clasts in the Fra Mauro Formation. To account for the porous, unwelded state of the Fra Mauro Formation, the ejecta must have been deposited at a temperature below that required for welding and annealing. Large boulders probably compacted by the Cone crater event occur near the rim of the crater. They probably consist of a similar suite of fragments, but are probably less porous than the formation. The geochronologic clocks of fragments in the Fra Mauro Formation, with textures ranging from unannealed to strongly annealed, were not reset or strongly modified by the Imbrian event. Strongly annealed breccia clasts and basalt clasts are pre-Imbrian, and probably existed as ejecta mixed with basalt flows in the Imbrium Basin prior to the Imbrian event. The Imbrian event probably occurred between 3.90 or 3.88 and 3.65 b.y. ago.

Frazzled/DCC facilitates cardiac cell outgrowth and attachment during Drosophila dorsal vessel formation.

PubMed

Macabenta, Frank D; Jensen, Amber G; Cheng, Yi-Shan; Kramer, Joseph J; Kramer, Sunita G

2013-08-15

Drosophila embryonic dorsal vessel (DV) morphogenesis is a highly stereotyped process that involves the migration and morphogenesis of 52 pairs of cardioblasts (CBs) in order to form a linear tube. This process requires spatiotemporally-regulated localization of signaling and adhesive proteins in order to coordinate the formation of a central lumen while maintaining simultaneous adhesion between CBs. Previous studies have shown that the Slit/Roundabout and Netrin/Unc5 repulsive signaling pathways facilitate site-specific loss of adhesion between contralateral CBs in order to form a luminal space. However, the concomitant mechanism by which attraction initiates CB outgrowth and discrete localization of adhesive proteins remains poorly understood. Here we provide genetic evidence that Netrin signals through DCC (Deleted in Colorectal Carcinoma)/UNC-40/Frazzled (Fra) to mediate CB outgrowth and attachment and that this function occurs prior to and independently of Netrin/UNC-5 signaling. fra mRNA is expressed in the CBs prior to and during DV morphogenesis. Loss-of-fra-function results in significant defects in cell shape and alignment between contralateral CB rows. In addition, CB outgrowth and attachment is impaired in both fra loss- and gain-of-function mutants. Deletion of both Netrin genes (NetA and NetB) results in CB attachment phenotypes similar to fra mutants. Similar defects are also seen when both fra and unc5 are deleted. Finally we show that Fra accumulates at dorsal and ventral leading edges of paired CBs, and this localization is dependent upon Netrin. We propose that while repulsive guidance mechanisms contribute to lumen formation by preventing luminal domains from coming together, site-specific Netrin/Frazzled signaling mediates CB attachment. Copyright © 2013 Elsevier Inc. All rights reserved.

Volatiles on the surface of Apollo 15 green glass and trace-element distributions among Apollo 15 soils

NASA Technical Reports Server (NTRS)

Chou, C.-L.; Boynton, W. V.; Sundberg, L. L.; Wasson, J. T.

1975-01-01

Zn, Ge, Cd, In, and Au have been detected in surficial deposits on Apollo 15 green-glass spherules, and it is suggested that these deposits are condensates from the magmatic gas phase which was responsible for the pneumatic expulsion of the green glass from the lunar interior. Thermodynamic data indicate that chlorides and fluorides were the dominant forms of the volatile metals. The Ar-40x content of a nongreen-glass soil fraction is greater than that found in green-glass. Mare and low-K Fra Mauro basalts seem to be the most prominent components of Apollo 15 soil. The correlation of Zn with Ar-40x and with Pb-204 is studied, and the distribution of quartz-normative and olivine-normative basalts is considered.

[Experimental study of bacteriostatic activity of Chinese herbal medicines on primary cariogenic bacteria in vitro].

PubMed

Wang, S; Fan, M; Bian, Z

2001-09-01

To screen some Chinese herbal medicines for their inhibitory activity on cariogenic bacteria, and investigate their active ingredients, and measure their minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC). Active components were isolated from every tested Chinese herbal medicine by means of aqueous extraction and ethanolic extraction. Berberine was purified from Coptis chinensis Fra. Disk agar diffusion method was employed in screening herbs with inhibiting effect on cariogenic bacteria. MIC and MBC were determined by broth dilution method. Against Streptococcus mutans Ingbritt, MBCs of Magnolia officinalis ethanolic extract, Berberine, Coptis chinensis Fra aqueous extract and Coptis chinensis Fra ethanolic extract were 0.488, 0.625, 7.800 and 1.950 g/L respectively. Against Streptococcus sobrinus 6715, MBCs of Magnolia extract, Coptis chinensis Fra ethanolic extract, Rhus chinensis Mill ethanolic extract and Phellodendron chinen ethanolic extract were 0.488, 0.625, 1.950, 3.900, 3.900 and 3.900 g/L respectively. Against Actinomyces viscosus ATCC 19246, MBCs of Berberine, Coptis chinensis Fra aqueous extract, Coptis chinensis Fra ethanolic extract, Rheum palmatum L aqueous extract and Rheum palmatum L ethanolic extract were 1.250, 3.900, 3.900, 15.600 and 31.250 g/L respectively. Magnolia officinalis, Coptis chinensis Fran, Rheum palmatum L aqueous extracts exhibit strong inhibition on cariogenic bacteria. Magnolia officinalis ethanolic extract has the strongest bactericidal effects on Streptococcus mutans and Streptococcus sobrinus.

Effect of serotonin on the expression of antigens and DNA levels in Yersinia pestis cells with different plasmid content

NASA Astrophysics Data System (ADS)

Klueva, Svetlana N.; Korsukov, Vladimir N.; Schukovskaya, Tatyana N.; Kravtsov, Alexander L.

2004-08-01

Using flow cytometry (FCM) the influence of exogenous serotonin on culture growth, DNA content and fluorescence intensity of cells binding FITC-labelled plague polyclonal immunoglobulins was studied in Yersinia pestis EV (pFra+, pCad+, pPst+), Yersinia pestis KM218 (pFra-, pCad-, pPst-), Yersinia pestis KM 216 (pFra-, pCad-, pPst+). The results have been obtained by FCM showed serotonin accelerated Yersinia pestis EV (pFra+, pCad+, pPst+), Yersinia pestis KM218 (pFra-, pCad-, pPst-) culture growth during cultivation in Hottinger broth pH 7.2 at 28°C at concentration of 10-5 M. The presence of 10-5 M serotonin in nutrient broth could modulate DNA content in 37°C growing population of plague microbe independently of their plasmid content. Serotonin have been an impact on the distribution pattern of the cells according to their phenotypical characteristics, which was reflected in the levels of population heterogeneity in the intensity of specific immunofluorescence determined by FMC.

77 FR 9297 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

..., Durango & Silverton Narrow Gauge Railroad (DSNG) has petitioned the Federal Railroad Administration (FRA... petition Docket Number FRA-2012-0002. DSNG is a tourist railroad that operates between Durango and...

Microcomputer Based Ship-Board Gun Control System.

DTIC Science & Technology

1981-03-01

to0 CD 04 5. 6D3. bi t0 U3 3 3. A - a U3 vi4 . * ~ ~ ~ 1 z.. n . 0 4 OR *4 AnS 94 C.) 0 3 * 04 td ) . cu 4. P* 0r * 3 6* 04 to 0 f 3. 4 6-4 "a I c *0...0I td ..M U o -Oq I Z ) OM Pm , N ou POO 0 -4 I h 4 * W33 SVil lot I 4- ad2 13 41 *f 0 44 ac ci 0 IH 4n 0= U 04 o3 0, 3a V). cav% n oft af 44 0 A4A... td ) -zl- ~ 6N 0 l 4 44L CdP 9 ~CI (n l 4 t3 0. .4 vi~ n - 4 U :A -. c 14 w i cn v - V", v- C) 4A " =- " cL c. Ni 0.4 (n Z m a -I 11) Cd E4 r a. a

Human health risk from heavy metal via food crops consumption with wastewater irrigation practices in Pakistan.

PubMed

Khan, Muhammad Usman; Malik, Riffat Naseem; Muhammad, Said

2013-11-01

The current study was designed to investigate the potential human health risks associated with consumption of food crops contaminated with toxic heavy metals. Cadmium (Cd) concentration in surface soils; Cd, lead (Pb) and chromium (Cr) in the irrigation water and food crops were above permissible limits. The accumulation factor (AF) was >1 for manganese (Mn) and Pb in different food crops. The Health Risk Index (HRI) was >1 for Pb in all food crops irrigated with wastewater and tube well water. HRI >1 was also recorded for Cd in all selected vegetables; and for Mn in Spinacia oleracea irrigated with wastewater. All wastewater irrigated samples (soil and food crops) exhibited high relative contamination level as compared to samples irrigated with tube well water. Our results emphasized the need for pretreatment of wastewater and routine monitoring in order to avoid contamination of food crops from the wastewater irrigation system. Copyright © 2013 Elsevier Ltd. All rights reserved.

49 CFR 229.211 - Processing of petitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Docket Management System and posted on its Web site at http://www.regulations.gov. (3) In the event FRA..., FRA will consider proper documentation of competent engineering analysis, or practical demonstrations...

49 CFR 229.211 - Processing of petitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Docket Management System and posted on its Web site at http://www.regulations.gov. (3) In the event FRA..., FRA will consider proper documentation of competent engineering analysis, or practical demonstrations...

Air Force Global Weather Central System Architecture Study. Final System/Subsystem Summary Report. Volume 8. System Specification

DTIC Science & Technology

1976-03-01

Service , CSE, Scott AFB, IL 62225. aws, usaf ltr dtd 8 jul 1976 >- a. CD SYSTEM DEVELOPMENT CORPORATION 1/ 2500 Colorado Avenue Santa Monica...Government Agen-TfAf* 17 MAR 1976 cies only. Other requests for this document ’-^ must be referred to Air Weather Service /CSi^,, Scott Air Force...Air Force Communica- tions Service must be clear’y defined. The appropriate Air Force Conmunications Service Agency should be responsible for the

Structural Crashworthiness Standards Comparison: Grade Crossing Collision Scenarios

DOT National Transportation Integrated Search

2009-10-20

In support of the Federal Railroad Administrations (FRA) : Railroad Equipment Safety Program, American and European : grade-crossing collision scenarios were evaluated and : compared. Finite element analyses (FEA) were employed to : subject an FRA...

Unifying mechanism for different fibrotic diseases

PubMed Central

Wernig, Gerlinde; Chen, Shih-Yu; Cui, Lu; Van Neste, Camille; Tsai, Jonathan M.; Kambham, Neeraja; Vogel, Hannes; Natkunam, Yaso; Gilliland, D. Gary; Nolan, Garry; Weissman, Irving L.

2017-01-01

Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts. Expression of the related AP1 transcription factor FRA2 was restricted to pulmonary artery hypertension. Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple organs and steatohepatosis, which was dependent on sustained c-Jun expression. Single cell mass cytometry revealed that c-Jun activates multiple signaling pathways in mice, including pAkt and CD47, which were also induced in human disease. αCD47 antibody treatment and VEGF or PI3K inhibition reversed various organ c-Jun–mediated fibroses in vivo. These data suggest that c-JUN is a central molecular mediator of most fibrotic conditions. PMID:28424250

49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

Code of Federal Regulations, 2012 CFR

2012-10-01

... to pay the assessment; the impacts an assessment might exact on the entity's continued business; and... factors in communications with FRA concerning civil penalty cases. Long-term solutions to compliance...

49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

Code of Federal Regulations, 2013 CFR

2013-10-01

... to pay the assessment; the impacts an assessment might exact on the entity's continued business; and... factors in communications with FRA concerning civil penalty cases. Long-term solutions to compliance...

49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

Code of Federal Regulations, 2011 CFR

2011-10-01

... to pay the assessment; the impacts an assessment might exact on the entity's continued business; and... factors in communications with FRA concerning civil penalty cases. Long-term solutions to compliance...

Evaluation of FRA trespass prevention research study

DOT National Transportation Integrated Search

2015-06-01

The United States Department of Transportations (US DOT) John A. Volpe National Transportation Systems Center (Volpe Center), under the direction of the US DOT Federal Railroad Administration (FRA) Office of Research and Development (R&D), conduct...

Rail transportation : Federal Railroad Administration's safety programs

DOT National Transportation Integrated Search

1998-05-20

Federal Railroad Administration (FRA) enforces federal railroad safety statutes under a delegation of authority from the Secretary of Transportation. FRA's mission is to protect railroad employees and the public by ensuring the safe operation of frei...

Improving Transportation Through Railroad Research : 1988-1991.

DOT National Transportation Integrated Search

1992-07-01

The Office of Research and Development (R&D) of the Federal Railroad Administration (FRA) conducts research, development, test, and evaluation projects to directly support the FRA's safety responsibility and to enhance the railroad system as a signif...

Accident/incident bulletin : calendar year 1995

DOT National Transportation Integrated Search

1996-08-01

Railroads must file monthly accident/incident reports with the Federal Railroad Administrations (FRA) Office of Safety. Bulletin 164 is a summary of accident/incident data reported by 679 railroads for calendar year 1995. The FRA Guide for Prepari...

Rail-car impact tests with steel coil : car crush

DOT National Transportation Integrated Search

2003-04-22

Two grade-crossing impact tests were conducted in June 2002 at the Federal Railroad Administration's (FRA's) Transportation Technology Center in Pueblo, Colorado as part of the FRA's research into passenger equipment crashworthiness. In both of these...

Efficient access pricing for rail bottlenecks

DOT National Transportation Integrated Search

2000-06-01

This study, which is posted online, was undertaken at the request of the Federal Railroad Administration (FRA), specifically the Office of the Associate Administrator for Policy and Program Development. The FRA Policy Office asked for a review of som...

77 FR 30047 - Petition for Alternative Locomotive Crashworthiness Design

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-21

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0036..., the National Railroad Passenger Corporation (Amtrak) has petitioned the Federal Railroad Administration (FRA) for approval of alternative locomotive crashworthiness design for an electric locomotive...

Update from C3RS lessons learned team : four demonstration pilots.

DOT National Transportation Integrated Search

2014-07-01

The Federal Railroad Administration (FRA) believes that, in addition to process and technology innovations, human-factors-based solutions can significantly contribute to improving safety in the railroad industry. To test this assumption, FRA implemen...

Crippling test of a Budd Pioneer passenger car

DOT National Transportation Integrated Search

2012-04-16

This research program was sponsored by the Federal Railroad Administration (FRA) Office of Research and Development in support of the advancement of improved safety standards for passenger rail vehicles. FRA and the Volpe National Transportation Syst...

76 FR 50359 - Hours of Service of Railroad Employees; Substantive Regulations for Train Employees Providing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-12

...FRA is amending its hours of service recordkeeping regulations, to add substantive hours of service regulations, including maximum on-duty periods, minimum off-duty periods, and other limitations, for train employees (e.g., locomotive engineers and conductors) providing commuter and intercity rail passenger transportation. The new substantive regulations require that railroads employing such train employees analyze and mitigate the risks for fatigue in the schedules worked by these train employees, and that the railroads submit to FRA for its approval the relevant schedules and fatigue mitigation plans. This final rule also makes corresponding changes to FRA's hours of service recordkeeping regulation, to require railroads to keep hours of service records and report excess service to FRA in a manner consistent with the new substantive requirements. This regulation is authorized by the Rail Safety Improvement Act of 2008.

Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells

PubMed Central

Tam, Wai Leong; Lu, Haihui; Buikhuisen, Joyce; Soh, Boon Seng; Lim, Elgene; Reinhardt, Ferenc; Wu, Zhenhua Jeremy; Krall, Jordan A.; Bierie, Brian; Guo, Wenjun; Chen, Xi; Liu, Xiaole Shirley; Brown, Myles; Lim, Bing; Weinberg, Robert A.

2014-01-01

SUMMARY The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C α (PKCα) specifically targets CSCs, but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling, and results in the PKCα-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKCα and FRA1 expression is associated with the aggressive triple-negative breast cancers and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs. PMID:24029232

Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells.

PubMed

Tam, Wai Leong; Lu, Haihui; Buikhuisen, Joyce; Soh, Boon Seng; Lim, Elgene; Reinhardt, Ferenc; Wu, Zhenhua Jeremy; Krall, Jordan A; Bierie, Brian; Guo, Wenjun; Chen, Xi; Liu, Xiaole Shirley; Brown, Myles; Lim, Bing; Weinberg, Robert A

2013-09-09

The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C α (PKCα) specifically targets CSCs but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling and results in the PKCα-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKCα and FRA1 expression is associated with the aggressive triple-negative breast cancers, and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs. Copyright © 2013 Elsevier Inc. All rights reserved.

Early development in males with Fragile X syndrome: a review of the literature.

PubMed

Kau, Alice S M; Meyer, Walter A; Kaufmann, Walter E

2002-05-01

This article reviews the current bibliographic knowledge on early neurobehavioral development and milestones in Fragile X syndrome (FraX), with emphasis on males affected by the condition. Three broad areas of early development were examined: (1) gross and fine motor, (2) speech and language, and (3) social. The result of the current review indicates very limited information on the developmental milestones in all three areas. The scarce literature on motor development shows that in FraX there is an early developmental delay. Research on speech and language demonstrates pervasive deficits in conversational skills and severe developmental delay, with increasing discrepancy between language level and chronological age in young males with FraX. Finally, deficits in social development in FraX include abnormal gaze, approach and avoidance conflict, and high incidence of autistic spectrum disorders. Copyright 2002 Wiley-Liss, Inc.

Intercellular Diffusion of a Fluorescent Sucrose Analog via the Septal Junctions in a Filamentous Cyanobacterium

PubMed Central

Nürnberg, Dennis J.; Mariscal, Vicente; Bornikoel, Jan; Nieves-Morión, Mercedes; Krauß, Norbert; Herrero, Antonia

2015-01-01

ABSTRACT Many filamentous cyanobacteria produce specialized nitrogen-fixing cells called heterocysts, which are located at semiregular intervals along the filament with about 10 to 20 photosynthetic vegetative cells in between. Nitrogen fixation in these complex multicellular bacteria depends on metabolite exchange between the two cell types, with the heterocysts supplying combined-nitrogen compounds but dependent on the vegetative cells for photosynthetically produced carbon compounds. Here, we used a fluorescent tracer to probe intercellular metabolite exchange in the filamentous heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. We show that esculin, a fluorescent sucrose analog, is incorporated by a sucrose import system into the cytoplasm of Anabaena cells. The cytoplasmic esculin is rapidly and reversibly exchanged across vegetative-vegetative and vegetative-heterocyst cell junctions. Our measurements reveal the kinetics of esculin exchange and also show that intercellular metabolic communication is lost in a significant fraction of older heterocysts. SepJ, FraC, and FraD are proteins located at the intercellular septa and are suggested to form structures analogous to gap junctions. We show that a ΔsepJ ΔfraC ΔfraD triple mutant shows an altered septum structure with thinner septa but a denser peptidoglycan layer. Intercellular diffusion of esculin and fluorescein derivatives is impaired in this mutant, which also shows a greatly reduced frequency of nanopores in the intercellular septal cross walls. These findings suggest that FraC, FraD, and SepJ are important for the formation of junctional structures that constitute the major pathway for feeding heterocysts with sucrose. PMID:25784700

Structural and Biochemical Insights into the Multiple Functions of Yeast Grx3.

PubMed

Chi, Chang-Biao; Tang, YaJun; Zhang, Jiahai; Dai, Ya-Nan; Abdalla, Mohnad; Chen, Yuxing; Zhou, Cong-Zhao

2018-04-13

The yeast Saccharomyces cerevisiae monothiol glutaredoxin Grx3 plays a key role in cellular defense against oxidative stress and more importantly, cooperates with BolA-like iron repressor of activation protein Fra2 to regulate the localization of the iron-sensing transcription factor Aft2. The interplay among Grx3, Fra2 and Aft2 responsible for the regulation of iron homeostasis has not been clearly described. Here we solved the crystal structures of the Trx domain (Grx3 Trx ) and Grx domain (Grx3 Grx ) of Grx3 in addition to the solution structure of Fra2. Structural analyses and activity assays indicated that the Trx domain also contributes to the glutathione S-transferase activity of Grx3, via an inter-domain disulfide bond between Cys37 and Cys176. NMR titration and pull-down assays combined with surface plasmon resonance experiments revealed that Fra2 could form a noncovalent heterodimer with Grx3 via an interface between the helix-turn-helix motif of Fra2 and the C-terminal segment of Grx3 Grx , different from the previously identified covalent heterodimer mediated by Fe-S cluster. Comparative affinity assays indicated that the interaction between Fra2 and Aft2 is much stronger than that between Grx3 and Aft2, or Aft2 toward its target DNA. These structural and biochemical analyses enabled us to propose a model how Grx3 executes multiple functions to coordinate the regulation of Aft2-controlled iron metabolism. Copyright © 2018 Elsevier Ltd. All rights reserved.

75 FR 3959 - Railroad Safety Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-25

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket No. FRA-2000-7257; Notice No. 58] Railroad Safety Advisory Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Railroad Safety Advisory Committee...

Railroad safety program Federal Railroad Administration OIG audit report

DOT National Transportation Integrated Search

1996-12-19

FRA's inspection and enforcement of Federal railroad safety standards were not effective and did not ensure railroads complied with safety standards. The Office of the Inspector General (OIG) found FRA inspectors did not cover areas necessary to ensu...

78 FR 78275 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2014

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... to data from FRA's Management Information System, the rail industry's random drug testing positive... December 26, 2013. FOR FURTHER INFORMATION CONTACT: Jerry Powers, FRA Drug and Alcohol Program Manager, W38...

FRA methods and approaches in environmental analysis and critical NEPA procedures

DOT National Transportation Integrated Search

2017-01-27

The Federal Railroad Administration hosted the third FRA Rail Program Delivery Meetinga 2.5-day conference for grantees, railroad representatives, federal oversight contractors, and staff, focused on rail project implementation. Below is a list of...

Stimulating safety culture change in four field demonstration pilots

DOT National Transportation Integrated Search

2010-01-01

Approximately 10 years ago, FRA began investigating organizational culture. Subsequent reorganization of the Volpe Center and HF Program to include Org. Culture & Safety Performance program. This is a summary of FRA field evaluations on the impact of...

Update from C3RS lessons learned team : safety culture and trend analysis.

DOT National Transportation Integrated Search

2014-07-01

The Federal Railroad Administration (FRA) believes that, in addition to process and technology innovations, human-factors-based solutions can significantly contribute to improving safety in the railroad industry. To test this assumption, FRA implemen...

77 FR 28421 - Railroad Safety Advisory Committee; Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-14

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket No. FRA-2000-7257: Notice No. 70] Railroad Safety Advisory Committee; Charter Renewal AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Charter Renewal of the Railroad Safety Advisory...

75 FR 27053 - Railroad Safety Advisory Committee; Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket No. FRA-2000-7257; Notice No. 61] Railroad Safety Advisory Committee; Charter Renewal AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Charter Renewal of the Railroad Safety Advisory...

49 CFR 262.15 - Environmental assessment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... FRA to approve a project for physical construction. FRA's “Procedures for Considering Environmental... and historic preservation review requirements. (b) States have two options for proceeding with environmental/historic preservation reviews. A State may file an application under subsection § 262.11 seeking...

Safety assurance and compliance program (SACP) : accomplishments for CY 2001

DOT National Transportation Integrated Search

2002-08-01

This recent research report by the Federal Railroad Administration (FRA), posted online, provides ease of access to information on the Safety Assurance and Compliance Program. The FRA promotes and helps ensure the safety of the nation's railroad indu...

2012 right-of-way fatality & trespass prevention workshop

DOT National Transportation Integrated Search

2013-04-30

Based on the success of the 2008 Trespasser Workshop, FRA and FTA sponsored this follow-on workshop. The keynote speech by FRA Administrator, Mr. Joseph C. Szabo, was followed by 23 technical presentations in the areas of Pedestrian Safety, Hazard Ma...

77 FR 10799 - Revised Guidance for Requesting One-Time Movement (OTM) Approvals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Revised Guidance for Requesting One-Time Movement (OTM) Approvals AGENCY: Federal Railroad Administration (FRA), Department of... as one-time movement approvals (OTMA). Recently, FRA revised its OTMA procedures to streamline the...

77 FR 3326 - Northeast Corridor Safety Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

.... 3] Northeast Corridor Safety Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of Northeast Corridor Safety Committee Meeting. SUMMARY: FRA announced the first meeting of the Northeast Corridor Safety Committee, a Federal...

76 FR 32391 - Northeast Corridor Safety Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

.... 1] Northeast Corridor Safety Committee; Notice of Meeting AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Announcement of the Northeast Corridor Safety Committee Meeting. SUMMARY: FRA announces the first meeting of the Northeast Corridor Safety Committee, a...

Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance.

PubMed

Organisti, Cristina; Hein, Irina; Grunwald Kadow, Ilona C; Suzuki, Takashi

2015-01-01

During central nervous system development, several guidance cues and receptors, as well as cell adhesion molecules, are required for guiding axons across the midline and along the anterior-posterior axis. In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors. Despite their importance, lack of Net or fra affects only some commissures, suggesting that additional molecules can fulfill this function. Recently, planar cell polarity (PCP) proteins have been implicated in midline axon guidance in both vertebrate and invertebrate systems. Here, we report that the atypical cadherin and PCP molecule Flamingo/Starry night (Fmi/Stan) acts jointly with Net/Fra signaling during midline development. Additional removal of fmi strongly increases the guidance defects in Net/fra mutants. Rescue and domain deletion experiments suggest that Fmi signaling facilitates commissural pathfinding potentially by mediating axonal fasciculation in a partly homophilic manner. Altogether, our results indicate that contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development. © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Task-switching deficits and repetitive behaviour in genetic neurodevelopmental disorders: data from children with Prader-Willi syndrome chromosome 15 q11-q13 deletion and boys with Fragile X syndrome.

PubMed

Woodcock, Kate A; Oliver, Chris; Humphreys, Glyn W

2009-03-01

Prader-Willi syndrome (PWS) and Fragile X syndrome (FraX) are associated with distinctive cognitive and behavioural profiles. We examined whether repetitive behaviours in the two syndromes were associated with deficits in specific executive functions. PWS, FraX, and typically developing (TD) children were assessed for executive functioning using the Test of Everyday Attention for Children and an adapted Simon spatial interference task. Relative to the TD children, children with PWS and FraX showed greater costs of attention switching on the Simon task, but after controlling for intellectual ability, these switching deficits were only significant in the PWS group. Children with PWS and FraX also showed significantly increased preference for routine and differing profiles of other specific types of repetitive behaviours. A measure of switch cost from the Simon task was positively correlated to scores on preference for routine questionnaire items and was strongly associated with scores on other items relating to a preference for predictability. It is proposed that a deficit in attention switching is a component of the endophenotypes of both PWS and FraX and is associated with specific behaviours. This proposal is discussed in the context of neurocognitive pathways between genes and behaviour.

Development of a hazard-based method for evaluating the fire safety of passenger trains

DOT National Transportation Integrated Search

1999-01-01

The fire safety of U.S. passenger rail trains currently is addressed through small-scale flammability and smoke emission tests and performance criteria promulgated by the Federal Railroad Administration (FRA). The FRA approach relies heavily on test ...

FRA funded grade crossing safety & trespass prevention research (June 2007 - present).

DOT National Transportation Integrated Search

2015-05-01

FRAs Office of R&D and Office of Railroad : Safety have been actively supporting highway-rail grade crossing safety and trespass : prevention research to improve safety. Below : is a list of technical reports and research results : from FRA-funded...

Fire safety of passenger trains : phase I : material evaluation (cone calorimeter)

DOT National Transportation Integrated Search

1999-01-01

As part of the passenger equipment rulemaking required by Congress, the Federal Railroad Administration (FRA) has proposed that its existing fire safety guidelines be made mandatory. A major conclusion of a FRA-funded 1993 study by the National Insti...

76 FR 15362 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-21

... DEPARTMENT OF TRANSPORTATION [Docket No. FRA-2011-0001-N-3] Federal Railroad Administration... (FRA), Department of Transportation (DOT). ACTION: Notice and request for comments. SUMMARY: In... numbers are not toll-free.) SUPPLEMENTARY INFORMATION: The Paperwork Reduction Act of 1995 (PRA), Public...

77 FR 69923 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-21

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0069... Rail d.b.a. Toledo Lake Erie and Western Railway (TLEW) has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad safety...

76 FR 34802 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-14

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2005-21613... amending document dated May 3, 2011, the Association of American Railroads (AAR) has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad...

78 FR 21705 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0097] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR... Federal Railroad Administration (FRA) for a waiver of compliance from certain [[Page 21706

75 FR 39617 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Petition for Waiver of Compliance In... Federal Railroad Administration (FRA) has received a request for a waiver of compliance from certain...-2010-0105] The Middletown & Hummelstown Railroad (MIDH) has petitioned FRA for a waiver of compliance...

75 FR 20035 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-16

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Petition for Waiver of Compliance In... Federal Railroad Administration (FRA) has received a request for a waiver of compliance from certain... safety requirements. Jasper petitioned FRA for a waiver of compliance from certain provisions of the...

Remedial Investigation Report, Presidio Main Installation, Presidio of San Francisco. Volume 6: Appendices A-F

DTIC Science & Technology

1997-01-01

Version 1 .0 )9-/77 Background data analysis Az. CdB . C t_ I eF2 G S21.4 Cal-Ba Method• detection limit Mediki czi.ii- 23.6 Cl-B O.. 13.9ol DATA15 Ca...E F G H T2 4124 CoI-Cr TTL5 i.2 305 0-0 Ca=Lonomllmen97.534 Create ineprt 41.1 Cal-Cr ENTER DATA 7 J42,8251 Histogram 41.2 Wa-0 IT 42.1 Cdct Ditibto

Infrared Measurement Variability Analysis.

DTIC Science & Technology

1980-09-01

collecting optics of the measurement system. The first equation for tile blackbody experiment has the form 4.0 pim _ Ae W ,T) r(X,D) 3.5 pm - 4.0 pm JrD2 f3.5...potential for noise reduction by identifying and reducing contributing system effects. The measurement variance ott . of an infinite population of possible...irradiance can be written 4.0 pm I r()A A+ A ) 2 4.0 X C1(, = W(XT + AT)d 3.5 pim I since c + Af =2 r +Ar I Using the two expressions juSt devclopCd

Alteration of Oriented Deposition of Cellulose Microfibrils by Mutation of a Katanin-Like Microtubule-Severing Protein

PubMed Central

Burk, David H.; Ye, Zheng-Hua

2002-01-01

It has long been hypothesized that cortical microtubules (MTs) control the orientation of cellulose microfibril deposition, but no mutants with alterations of MT orientation have been shown to affect this process. We have shown previously that in Arabidopsis, the fra2 mutation causes aberrant cortical MT orientation and reduced cell elongation, and the gene responsible for the fra2 mutation encodes a katanin-like protein. In this study, using field emission scanning electron microscopy, we found that the fra2 mutation altered the normal orientation of cellulose microfibrils in walls of expanding cells. Although cellulose microfibrils in walls of wild-type cells were oriented transversely along the elongation axis, cellulose microfibrils in walls of fra2 cells often formed bands and ran in different directions. The fra2 mutation also caused aberrant deposition of cellulose microfibrils in secondary walls of fiber cells. The aberrant orientation of cellulose microfibrils was shown to be correlated with disorganized cortical MTs in several cell types examined. In addition, the thickness of both primary and secondary cell walls was reduced significantly in the fra2 mutant. These results indicate that the katanin-like protein is essential for oriented cellulose microfibril deposition and normal cell wall biosynthesis. We further demonstrated that the Arabidopsis katanin-like protein possessed MT-severing activity in vitro; thus, it is an ortholog of animal katanin. We propose that the aberrant MT orientation caused by the mutation of katanin results in the distorted deposition of cellulose microfibrils, which in turn leads to a defect in cell elongation. These findings strongly support the hypothesis that cortical MTs regulate the oriented deposition of cellulose microfibrils that determines the direction of cell elongation. PMID:12215512

Alteration of oriented deposition of cellulose microfibrils by mutation of a katanin-like microtubule-severing protein.

PubMed

Burk, David H; Ye, Zheng-Hua

2002-09-01

It has long been hypothesized that cortical microtubules (MTs) control the orientation of cellulose microfibril deposition, but no mutants with alterations of MT orientation have been shown to affect this process. We have shown previously that in Arabidopsis, the fra2 mutation causes aberrant cortical MT orientation and reduced cell elongation, and the gene responsible for the fra2 mutation encodes a katanin-like protein. In this study, using field emission scanning electron microscopy, we found that the fra2 mutation altered the normal orientation of cellulose microfibrils in walls of expanding cells. Although cellulose microfibrils in walls of wild-type cells were oriented transversely along the elongation axis, cellulose microfibrils in walls of fra2 cells often formed bands and ran in different directions. The fra2 mutation also caused aberrant deposition of cellulose microfibrils in secondary walls of fiber cells. The aberrant orientation of cellulose microfibrils was shown to be correlated with disorganized cortical MTs in several cell types examined. In addition, the thickness of both primary and secondary cell walls was reduced significantly in the fra2 mutant. These results indicate that the katanin-like protein is essential for oriented cellulose microfibril deposition and normal cell wall biosynthesis. We further demonstrated that the Arabidopsis katanin-like protein possessed MT-severing activity in vitro; thus, it is an ortholog of animal katanin. We propose that the aberrant MT orientation caused by the mutation of katanin results in the distorted deposition of cellulose microfibrils, which in turn leads to a defect in cell elongation. These findings strongly support the hypothesis that cortical MTs regulate the oriented deposition of cellulose microfibrils that determines the direction of cell elongation.

75 FR 4703 - Track Safety Standards; Continuous Welded Rail (CWR)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration 49 CFR Part 213 [Docket No. FRA-2008-0036] RIN 2130-AB90 Track Safety Standards; Continuous Welded Rail (CWR) AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Final rule; response to petition for...

49 CFR 260.29 - Third party consultants.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Applications for Financial Assistance § 260.29 Third party consultants. Applicants may utilize independent third-party consultants to prepare a financial evaluation of... assist FRA in the evaluation of the application and would significantly reduce the time necessary for FRA...

75 FR 76070 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

...'s arguments in favor of relief. American Short Line and Regional Railroad Association [Waiver Petition Docket Number FRA-2009-0078] In response to the American Short Line and Regional Railroad Association's (ASLRRA) July 16, 2009, petition in this docket, FRA granted certain identified ASLRRA member...

77 FR 48591 - State Rail Plan Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Plan Guidance AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Request for Public Comment on Proposed State Rail Plan Guidance. SUMMARY: FRA is publishing this notice to... plans. State rail plans are documents that are required under Section 303 of the Passenger Rail...

76 FR 71432 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-17

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... any correspondence submitted. FRA will summarize comments received in response to this notice in a... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

77 FR 25783 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-01

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0034] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR..., Iowa (City), has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from...

77 FR 25228 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0030] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR..., CA (City), has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from...

76 FR 38453 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-30

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [ Docket Number FRA-2011-0049] Petition for Waiver of Compliance In accordance with part 211 of Title 49 of the Code of Federal... railroads has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from certain...

77 FR 25228 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-27

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0031] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR... Sacramento, CA (City), has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance...

76 FR 21096 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2010-0152] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 of the Code of Federal... initial boundaries, see FRA's Notice of Petition for Waiver of Compliance published on November 2, 2010...

78 FR 28283 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-14

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2013-0006] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR... Company (PICK) has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from...

77 FR 43645 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0052] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 of the Code of Federal... (FRA) for a waiver of compliance from certain Federal hours of service requirements for train employees...

Characterization and expression of a metallothionein gene in the aquatic fern Azolla filiculoides under heavy metal stress.

PubMed

Schor-Fumbarov, Tamar; Goldsbrough, Peter B; Adam, Zach; Tel-Or, Elisha

2005-12-01

A cDNA encoding a type 2 metallothionein (MT) was isolated from Azolla filiculoides, termed AzMT2, accession no. AF482470. The AzMT2 transcript was expressed in sterile A. filiculoides that were free of the cyanobiont Anabaena azollae after erythromycin treatment, proving that AzMT2 is encoded by the fern genome. AzMT2 RNA expression was enhanced by the addition of Cd(+2), Cu(+2), Zn(+2) and Ni(+2) to the growth medium. The transcript level of AzMT2 correlated with the metal content in the plants. Temporal analysis of AzMT2 expression demonstrated that Cd(2+) and Ni(2+) induction of AzMT2 RNA expression occurred within 48 h. AzMT2-enhanced expression responded more intensely to the toxic Cd and Ni ions in A. filiculoides suggesting that AzMT2 may participate in detoxification mechanism. The more moderate response of AzMT2 to Zn and Cu ions, which are essential micronutrients, suggest a role for AzMT2 in metal homeostasis.

49 CFR Appendix C to Part 209 - FRA's Policy Statement Concerning Small Entities

Code of Federal Regulations, 2014 CFR

2014-10-01

... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY ENFORCEMENT PROCEDURES Pt. 209, App... history of compliance, FRA inspectors consider “such other factors as the immediate circumstances make... eliminating the safety hazard; the entity's culpability; the entity's compliance history; the entity's ability...

76 FR 41555 - Tupelo, Mississippi Railroad Relocation Project

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... Parts 1500-1508, and the FRA NEPA procedures, 64 FR 28545 (May 26, 1999). FRA is the lead Federal agency and the Mississippi Department of Transportation (MDOT) is the lead State agency. The Environmental... minimize potential impacts. Such strategies would be further refined in subsequent environmental review...

77 FR 45715 - Notice of Public Hearing: Reading Blue Mountain and Northern Railroad

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2003-15754] Notice of Public Hearing: Reading Blue Mountain and Northern Railroad The Reading Blue Mountain and Northern Railroad (RBMN) has petitioned the Federal Railroad Administration (FRA) seeking the approval of the...

77 FR 22843 - Notice of Product Development

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration [Docket Number FRA-2012-0020] Notice of Product Development In accordance with Part 211 of Title 49 Code of Federal Regulations (CFR... Administration (FRA) a Notice of Product Development per 49 CFR 236.913(d)(1)(i) for the modification of the...

49 CFR 229.207 - New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive crashworthiness design standards. 229.207 Section 229... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Locomotive Crashworthiness...

49 CFR 229.207 - New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive crashworthiness design standards. 229.207 Section 229... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Locomotive Crashworthiness...

49 CFR 229.207 - New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive crashworthiness design standards. 229.207 Section 229... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Locomotive Crashworthiness...

49 CFR 229.207 - New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false New locomotive crashworthiness design standards and changes to existing FRA-approved locomotive crashworthiness design standards. 229.207 Section 229... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Locomotive Crashworthiness...

78 FR 54951 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-06

... waiver of compliance from certain provisions of the Federal railroad safety regulations contained at 49 CFR Part 215-Railroad Freight Car Safety Standards. FRA assigned the petition Docket Number FRA-2013- 0065. TEVR seeks relief from 49 CFR 215.303-Stenciling of restricted cars, which requires that...

77 FR 58440 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... Savage Industrial Rail Services Operation (Savage) has petitioned the Federal Railroad Administration... to 184 days. Savage conducts rail switching operations for customers in the area of Henderson and... customers. FRA assigned the petition Docket Number FRA-2012-0063. A copy of the petition, as well as any...

76 FR 78732 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

... or modification of a signal system. FRA has assigned the petition Docket Number FRA-2011-0092. CSX seeks approval of the proposed modification of the bridge tender controlled signals to automatic signals..., Jacksonville Division. The modification consists of the conversion of bridge tender controlled signals to...

49 CFR 219.608 - FRA Administrator's determination of random alcohol testing rate.

Code of Federal Regulations, 2012 CFR

2012-10-01

... alcohol testing rate. 219.608 Section 219.608 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.608 FRA Administrator's determination of random alcohol...

49 CFR 219.608 - FRA Administrator's determination of random alcohol testing rate.

Code of Federal Regulations, 2011 CFR

2011-10-01

... alcohol testing rate. 219.608 Section 219.608 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.608 FRA Administrator's determination of random alcohol...

49 CFR 219.608 - FRA Administrator's determination of random alcohol testing rate.

Code of Federal Regulations, 2014 CFR

2014-10-01

... alcohol testing rate. 219.608 Section 219.608 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.608 FRA Administrator's determination of random alcohol...

49 CFR 219.608 - FRA Administrator's determination of random alcohol testing rate.

Code of Federal Regulations, 2010 CFR

2010-10-01

... alcohol testing rate. 219.608 Section 219.608 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.608 FRA Administrator's determination of random alcohol...

49 CFR 219.608 - FRA Administrator's determination of random alcohol testing rate.

Code of Federal Regulations, 2013 CFR

2013-10-01

... alcohol testing rate. 219.608 Section 219.608 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CONTROL OF ALCOHOL AND DRUG USE Random Alcohol and Drug Testing Programs § 219.608 FRA Administrator's determination of random alcohol...

75 FR 51525 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

.... 63] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of RSAC's Working.... SUPPLEMENTARY INFORMATION: This notice serves to update FRA's last announcement of working group activities and...

49 CFR Appendix C to Part 230 - FRA Inspection Forms

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false FRA Inspection Forms C Appendix C to Part 230 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Pt. 230, App. C Appendix C...

49 CFR Appendix C to Part 230 - FRA Inspection Forms

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false FRA Inspection Forms C Appendix C to Part 230 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Pt. 230, App. C Appendix C...

49 CFR Appendix C to Part 230 - FRA Inspection Forms

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Inspection Forms C Appendix C to Part 230 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Pt. 230, App. C Appendix C...

76 FR 70532 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... correspondence submitted. FRA will summarize comments received in response to this notice in a subsequent notice... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

78 FR 76190 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

... received will advance three objectives: (i) reduce reporting burdens; (ii) ensure that it organizes.... FRA will summarize comments received in response to this notice in a subsequent notice and include... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

75 FR 3275 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... submitted. FRA will summarize comments received in response to this notice in a subsequent notice and... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

78 FR 59086 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

... comments received will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it... correspondence submitted. FRA will summarize comments received in response to this notice in a subsequent notice... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

The long non-coding RNA PARTICLE is associated with WWOX and the absence of FRA16D breakage in osteosarcoma patients.

PubMed

O'Leary, Valerie Bríd; Maugg, Doris; Smida, Jan; Baumhoer, Daniel; Nathrath, Michaela; Ovsepian, Saak Victor; Atkinson, Michael John

2017-10-20

Breakage of the fragile site FRA16D disrupts the WWOX (WW Domain Containing Oxidoreductase) tumor suppressor gene in osteosarcoma. However, the frequency of breakage is not sufficient to explain the rate of WWOX loss in pathogenesis. The involvement of non-coding RNA transcripts is proposed due to their accumulation at fragile sites, where they are advocated to influence specific chromosomal regions associated with malignancy. The long ncRNA PARTICLE (promoter of MAT2A antisense radiation-induced circulating long non-coding RNA) is transiently elevated in response to irradiation and influences epigenetic silencing modification within WWOX . It now emerges that elevated PARTICLE levels are significantly associated with FRA16D non-breakage in OS patients. Although not associated with overall survival, high PARTICLE levels were found to be significantly linked to metastasis free outcome. The transcription of both PARTICLE and WWOX are transiently responsive to exposure to low doses of radiation in osteosarcoma cell lines. Herein, a relationship between WWOX and PARTICLE transcription is suggested in human osteosarcoma cell lines representing alternative genetic backgrounds. PARTICLE over-expression ameliorated WWOX promoter activity in U2OS harboring FRA16D non-breakage. It can be concluded that the lncRNA PARTICLE influences the WWOX tumor suppressor and in the absence of WWOX FRA16D breakage, it is associated with OS metastasis-free survival.

Fracture network evaluation program (FraNEP): A software for analyzing 2D fracture trace-line maps

NASA Astrophysics Data System (ADS)

Zeeb, Conny; Gomez-Rivas, Enrique; Bons, Paul D.; Virgo, Simon; Blum, Philipp

2013-10-01

Fractures, such as joints, faults and veins, strongly influence the transport of fluids through rocks by either enhancing or inhibiting flow. Techniques used for the automatic detection of lineaments from satellite images and aerial photographs, LIDAR technologies and borehole televiewers significantly enhanced data acquisition. The analysis of such data is often performed manually or with different analysis software. Here we present a novel program for the analysis of 2D fracture networks called FraNEP (Fracture Network Evaluation Program). The program was developed using Visual Basic for Applications in Microsoft Excel™ and combines features from different existing software and characterization techniques. The main novelty of FraNEP is the possibility to analyse trace-line maps of fracture networks applying the (1) scanline sampling, (2) window sampling or (3) circular scanline and window method, without the need of switching programs. Additionally, binning problems are avoided by using cumulative distributions, rather than probability density functions. FraNEP is a time-efficient tool for the characterisation of fracture network parameters, such as density, intensity and mean length. Furthermore, fracture strikes can be visualized using rose diagrams and a fitting routine evaluates the distribution of fracture lengths. As an example of its application, we use FraNEP to analyse a case study of lineament data from a satellite image of the Oman Mountains.

49 CFR 240.103 - Approval of design of individual railroad programs by FRA.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Approval of design of individual railroad programs... (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF... individual railroad programs by FRA. (a) Each railroad shall submit its written certification program and a...

77 FR 29307 - Control of Alcohol and Drug Use: Addition of Post-Accident Toxicological Testing for Non...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-17

... post-accident testing, FRA routinely conducts tests for alcohol, marijuana, cocaine, phencyclidine (PCP..., as part of its accident investigation program, FRA has conducted post-accident alcohol and drug tests... conduct post-accident tests for any substance (e.g., carbon [[Page 29308

77 FR 65935 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... contained in 49 CFR part 230--Steam Locomotive Inspection and Maintenance Standards. FRA assigned the petition Docket Number FRA- 2012-0076. Steam Locomotive Number 2719 is a former Soo Line class H-23 4-6-2 ``Pacific'' type locomotive built by the American Locomotive Company in 1923. L&TPF restored Steam...

78 FR 77788 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... the petition, as well as any written communications concerning the petition, is available for review... are invited to participate in these proceedings by submitting written views, data, or comments. FRA... should notify FRA, in writing, before the end of the comment period and specify the basis for their...

77 FR 75699 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

..., the requirements for FRA Type I material in the forward and rearward end-facing glazing locations of the locomotive cab windshield as well as FRA Type II material in all side-facing windows of the... safety. A copy of the petition, as well as any written communications concerning the petition, is...

75 FR 1547 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2010

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

...: Notice of Determination. SUMMARY: Using data from Management Information System annual reports, FRA has... taken from FRA's Management Information System. Based on this data, the Administrator publishes a... effective upon publication. FOR FURTHER INFORMATION CONTACT: Lamar Allen, Alcohol and Drug Program Manager...

75 FR 79308 - Alcohol and Drug Testing: Determination of Minimum Random Testing Rates for 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... from Management Information System annual reports, FRA has determined that the 2009 rail industry... program data taken from FRA's Management Information System. Based on this data, the Administrator... effective December 20, 2010. FOR FURTHER INFORMATION CONTACT: Lamar Allen, Alcohol and Drug Program Manager...

FRA/Volpe Center task force observation of operations at TVE Transrapid test facility : October 15 to December 17, 1992

DOT National Transportation Integrated Search

1993-04-01

This report prepared in April 1993 describes the operations witnessed and the relevant information obtained by nine members of the FRA/Volpe Center High Speed Guided Ground Transportation Safety Task Force during 9 weeks of observation of maglev deve...

75 FR 68861 - Miscellaneous Amendments to the Federal Railroad Administration's Accident/Incident Reporting...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

... regulations addressing accident/incident reporting in order to clarify ambiguous regulations and to enhance the quality of information available for railroad casualty analysis. In addition, FRA has revised the... (telephone: 202-493- 1381). SUPPLEMENTARY INFORMATION: I. The FRA Guide and the Companion Guide In addition...

49 CFR 216.13 - Special notice for repairs-locomotive.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION SPECIAL NOTICE AND EMERGENCY ORDER PROCEDURES: RAILROAD TRACK... not safe to operate in the service to which it is put, whether by reason of nonconformity with the FRA Railroad Locomotive Safety Standards set forth in part 229 of this chapter or the FRA Railroad Locomotive...

49 CFR 242.103 - Approval of design of individual railroad programs by FRA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Approval of design of individual railroad programs by FRA. 242.103 Section 242.103 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF CONDUCTORS Program and Eligibility Requirements...

76 FR 66126 - Notice of Public Hearing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... of Public Hearing The Central Oregon and Pacific Railroad (CORP) has petitioned the Federal Railroad..., FRA has determined that a public hearing is necessary before a final decision is made on this proposal. Accordingly, FRA invites all interested persons to participate in a public hearing on December 1, 2011. The...

49 CFR 269.7 - Petitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... consistent with the time limitations described in § 269.3(c) of this part. (b) Petition Requirements. Each petition shall: (1) Be filed with FRA no later than 45 days after FRA provides notice of the Secretary's... after the later of the enactment of such statutory authority or the Secretary's issuance of the...

49 CFR 269.7 - Petitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... consistent with the time limitations described in § 269.3(c) of this part. (b) Petition Requirements. Each petition shall: (1) Be filed with FRA no later than 45 days after FRA provides notice of the Secretary's... after the later of the enactment of such statutory authority or the Secretary's issuance of the...

FRA/Volpe Center Task Force Observation of Operations at TVE Transrapid Test Facility, Addendum

DOT National Transportation Integrated Search

1993-12-01

This report is an addendum to a report (No. DOT-VNTSC-RR393-PM-93-1) prepared in April : 1993 describing the operations witnessed and the relevant information obtained by nine members : of the FRA/Volpe Center High Speed Guided Ground Transportation ...

78 FR 5767 - Positive Train Control Systems (RRR)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

... [Docket No. FRA-2011-0061, Notice No. 2] RIN 2130-AC32 Positive Train Control Systems (RRR) AGENCY... positive train control (PTC) systems. The present document clarifies FRA's responses to several elements of... control by signal indication or mandatory directive; that the movement of non-PTC equipped locomotives and...

76 FR 8699 - Locomotive Safety Standards; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

.... FRA-2009-0094 and FRA-2009-0095, Notice No. 2] RIN 2130-AC16 Locomotive Safety Standards; Correction... notifying the public that the correct docket number for the Locomotive Safety Standards notice of proposed... locomotive safety standards. See 76 FR 2200. The NPRM established a public docket to receive comments in...

77 FR 23159 - Locomotive Safety Standards; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

.... FRA-2009-0094 and FR-2009-0095, Notice No. 4] RIN 2130-AC16 Locomotive Safety Standards; Correction... notifying the public that the correct docket number for the Locomotive Safety Standards final rule is FRA... rule related to locomotive safety standards. See 77 FR 21312. The final rule established a public...

78 FR 28284 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-14

... Railway (CP) has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from... assigned the petition Docket Number FRA-2013-0040. Specifically, CP requests relief from 49 CFR 232.205(c... brake tests--1,000-mile inspection for trains operating in distributive power (DP) mode. CP requests...

49 CFR 219.211 - Analysis and follow-up.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Program Manager, Office of Safety, FRA, 1200 New Jersey Avenue, SE., Washington, DC 20590 within 45 days... Safety Board. (c) With respect to a surviving employee, a test reported as positive for alcohol or a... of each review to the Associate Administrator for Safety, FRA, Washington, DC 20590. Such report must...

49 CFR 225.25 - Recordkeeping.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Total number of cars that derailed; (20) Total amount of damage in dollars to equipment based on... damage in dollars to track, signal, way and structures based on computations as described in the “FRA... Equipment Accident/Incident Record (Form FRA F 6180.97) or an alternative railroad-designed record as...

75 FR 4904 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

...-7257] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of RSAC's Working... notice serves to update FRA's last announcement of working group activities and status reports of August...

77 FR 24257 - Railroad Safety Advisory Committee (RSAC); Working Group Activity Update

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

.... 69] Railroad Safety Advisory Committee (RSAC); Working Group Activity Update AGENCY: Federal Railroad... Committee (RSAC) Working Group Activities. SUMMARY: The FRA is updating its announcement of the RSAC Working.... SUPPLEMENTARY INFORMATION: This notice serves to update FRA's last announcement of working group activities and...

49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Pt. 229, App. C...

49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Pt. 229, App. C...

77 FR 35466 - Pilot Project Grants in Support of Railroad Safety Risk Reduction Programs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-13

... mobile telephones and laptop computers. This subpart was codified in response to an increase in the... FRA funding. Applications should include feasibility studies and cost estimates, if completed. FRA will more favorably consider applications that include these types of studies and estimates, as they...

49 CFR Appendix C to Part 229 - FRA Locomotive Standards-Code of Defects

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Locomotive Standards-Code of Defects C Appendix C to Part 229 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Pt. 229, App. C...

75 FR 32981 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-10

... will advance three objectives: (i) Reduce reporting burdens; (ii) ensure that it organizes information.... FRA will summarize comments received in response to this notice in a subsequent notice and include..., including whether the activities will have practical utility; (ii) the accuracy of FRA's estimates of the...

76 FR 38456 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-30

...] Petition for Waiver of Compliance In accordance with Part 211 of Title 49 of the Code of Federal... Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad safety...- 0048. TriMet has petitioned FRA for a waiver of compliance from certain provisions of the Federal...

HLA-DPB1*04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study.

PubMed

Hadley, David; Hagopian, William; Liu, Edwin; She, Jin-Xiong; Simell, Olli; Akolkar, Beena; Ziegler, Anette-G; Rewers, Marian; Krischer, Jeffrey P; Chen, Wei-Min; Onengut-Gumuscu, Suna; Bugawan, Teodorica L; Rich, Stephen S; Erlich, Henry; Agardh, Daniel

2015-06-01

Tissue transglutaminase autoantibodies (tTGAs) represent the first evidence of celiac disease (CD) development. Associations of HLA-DR3-DQA1*05:01-DQB1*02:01 (i.e., DR3-DQ2) and, to a lesser extent, DR4-DQA1*03:01-DQB1*03:02 (i.e., DR4-DQ8) with the risk of CD differ by country, consistent with additional genetic heterogeneity that further refines risk. Therefore, we examined human leukocyte antigen (HLA) factors other than DR3-DQ2 for their contribution to developing tTGAs. The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8,676 infants at an increased HLA-DR-DQ risk for type 1 diabetes and CD into a 15-year prospective surveillance follow-up. Of those followed up, 21% (n=1,813) carried DR3-DQ2/DR3-DQ2, 39% (n=3,359) carried DR3-DQ2/DR4-DQ8, 20% (n=1701) carried DR4-DQ8/DR4-DQ8, and 17% (n=1,493) carried DR4-DQ8/DQ4. Within TEDDY, a nested case-control design of 248 children with CD autoimmunity (CDA) and 248 matched control children were genotyped for HLA-B, -DRB3, -DRB4, -DPA1, and -DPB1 genes, and the entire cohort was genotyped for single-nucleotide polymorphisms (SNPs) using the Illumina ImmunoChip. CDA was defined as a positive tTGA test at two consecutive clinic visits, whereas matching in those with no evidence of tTGAs was based on the presence of HLA-DQ2, country, and sex. After adjustment for DR3-DQ2 and restriction to allele frequency (AF) ≥5%, HLA-DPB1*04:01 was inversely associated with CDA by conditional logistic regression (AF=44%, odds ratio=0.71, 95% confidence interval (CI)=0.53-0.96, P=0.025). This association of time to CDA and HLA-DPB1*04:01 was replicated with statistical significance in the remainder of the cohort using imputation for specific HLA alleles based on SNP genotyping (hazard ratio=0.84, 95% CI=0.73-0.96, P=0.013). HLA-DPB1*04:01 may reduce the risk of tTGAs, an early marker of CD, among DR3-DQ2 children, confirming that additional variants in the HLA region influence the risk for CDA.

Layout optimization with assist features placement by model based rule tables for 2x node random contact

NASA Astrophysics Data System (ADS)

Jun, Jinhyuck; Park, Minwoo; Park, Chanha; Yang, Hyunjo; Yim, Donggyu; Do, Munhoe; Lee, Dongchan; Kim, Taehoon; Choi, Junghoe; Luk-Pat, Gerard; Miloslavsky, Alex

2015-03-01

As the industry pushes to ever more complex illumination schemes to increase resolution for next generation memory and logic circuits, sub-resolution assist feature (SRAF) placement requirements become increasingly severe. Therefore device manufacturers are evaluating improvements in SRAF placement algorithms which do not sacrifice main feature (MF) patterning capability. There are known-well several methods to generate SRAF such as Rule based Assist Features (RBAF), Model Based Assist Features (MBAF) and Hybrid Assisted Features combining features of the different algorithms using both RBAF and MBAF. Rule Based Assist Features (RBAF) continue to be deployed, even with the availability of Model Based Assist Features (MBAF) and Inverse Lithography Technology (ILT). Certainly for the 3x nm node, and even at the 2x nm nodes and lower, RBAF is used because it demands less run time and provides better consistency. Since RBAF is needed now and in the future, what is also needed is a faster method to create the AF rule tables. The current method typically involves making masks and printing wafers that contain several experiments, varying the main feature configurations, AF configurations, dose conditions, and defocus conditions - this is a time consuming and expensive process. In addition, as the technology node shrinks, wafer process changes and source shape redesigns occur more frequently, escalating the cost of rule table creation. Furthermore, as the demand on process margin escalates, there is a greater need for multiple rule tables: each tailored to a specific set of main-feature configurations. Model Assisted Rule Tables(MART) creates a set of test patterns, and evaluates the simulated CD at nominal conditions, defocused conditions and off-dose conditions. It also uses lithographic simulation to evaluate the likelihood of AF printing. It then analyzes the simulation data to automatically create AF rule tables. It means that analysis results display the cost of different AF configurations as the space grows between a pair of main features. In summary, model based rule tables method is able to make it much easier to create rule tables, leading to faster rule-table creation and a lower barrier to the creation of more rule tables.

EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53.

PubMed

Bogusz, Agata M

2017-01-01

Posttransplant lymphoproliferative disorders (PTLDs) are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV). EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL) 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL) with abundant large, bizarre Hodgkin-like cells. By immunostaining, the malignant cells were immunoreactive for CD45, CD20, CD79a, PAX5, BCL6, MUM1, and p53 and negative for CD15, CD30, latent membrane protein 1 (LMP1), and EBV-encoded RNA (EBER). Flow cytometry demonstrated lambda light chain restricted CD5 and CD10 negative B-cells. Fluorescence in situ hybridization studies (FISH) were negative for cMYC , BCL2, and BCL6 rearrangements but showed deletion of TP53 and monosomy of chromosome 17. Next-generation sequencing studies (NGS) revealed numerous genetic alterations including 6 pathogenic mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53 (x2) genes and 30 variants of unknown significance (VOUS) in ABL1, ASXL1, ATM, BCOR, BCORL1, BRNIP3, CDH2, CDKN2A, DNMT3A, ETV6, EZH2, FBXW7, KIT, NF1, RUNX1, SETPB1, SF1, SMC1A, STAG2, TET2, TP53, and U2AF2.

EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53

PubMed Central

2017-01-01

Posttransplant lymphoproliferative disorders (PTLDs) are a diverse group of lymphoid or plasmacytic proliferations frequently driven by Epstein-Barr virus (EBV). EBV-negative PTLDs appear to represent a distinct entity. This report describes an unusual case of a 33-year-old woman that developed a monomorphic EBV-negative PTLD consistent with diffuse large B-cell lymphoma (DLBCL) 13 years after heart-lung transplant. Histological examination revealed marked pleomorphism of the malignant cells including nodular areas reminiscent of classical Hodgkin lymphoma (cHL) with abundant large, bizarre Hodgkin-like cells. By immunostaining, the malignant cells were immunoreactive for CD45, CD20, CD79a, PAX5, BCL6, MUM1, and p53 and negative for CD15, CD30, latent membrane protein 1 (LMP1), and EBV-encoded RNA (EBER). Flow cytometry demonstrated lambda light chain restricted CD5 and CD10 negative B-cells. Fluorescence in situ hybridization studies (FISH) were negative for cMYC, BCL2, and BCL6 rearrangements but showed deletion of TP53 and monosomy of chromosome 17. Next-generation sequencing studies (NGS) revealed numerous genetic alterations including 6 pathogenic mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53(x2) genes and 30 variants of unknown significance (VOUS) in ABL1, ASXL1, ATM, BCOR, BCORL1, BRNIP3, CDH2, CDKN2A, DNMT3A, ETV6, EZH2, FBXW7, KIT, NF1, RUNX1, SETPB1, SF1, SMC1A, STAG2, TET2, TP53, and U2AF2. PMID:28487787

Fatigue and alertness in the United States railroad industry part II: fatigue research in the Office of Research and Development at the Federal Railroad Administration

DOT National Transportation Integrated Search

2000-03-31

A new approach for improving safety in the U.S. railroad industry was initiated in the 1990's by the Federal Railroad Administration (FRA). The FRA has stressed cooperative partnerships with other federal agencies, railroad management, labor unions, ...

78 FR 46679 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-01

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0073. Applicant: Norfolk..., Georgia 30309. NS seeks approval of the proposed discontinuance of automatic signals within traffic...

77 FR 74736 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition docket number FRA-2012-0087... Street NE., Atlanta, Georgia 30309. NS seeks approval of the proposed discontinuance of automatic signals...

78 FR 59754 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-27

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0095. Applicant: Grenada Railway... seeks approval of the proposed discontinuance and removal of the automatic block signal (ABS) system...

78 FR 9106 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0099. Applicant: Norfolk...-throw switch. NS seeks to make these proposed changes to modernize its signal equipment and install...

77 FR 2774 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... modification of a signal system. FRA has reopened and assigned the application Docket Number FRA-2003-15754. Applicant: Reading, Blue Mountain and Northern Railroad, Mr. Jonathan Barket, AVP, Communications & Signals...

77 FR 48204 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-13

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... modification of a signal system. FRA assigned the petition docket number FRA-2012-0064. Applicant: Union Pacific Railroad Company, Mr. Phillip A. Danner, AVP Engineering-Signal, 1400 Douglas Street, MS 0910...

78 FR 14874 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-07

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0017. Applicant: Norfolk..., Georgia 30309. NS seeks approval of the proposed temporary discontinuance of the signal system at the...

78 FR 77785 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA-2013-0125. Applicants: Union Pacific Railroad, Mr. Phillip A. Danner, AVP Engineering-Signal, 1400 Douglas Street, MS...

77 FR 9296 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0012. UP seeks approval of the proposed discontinuance of the automatic block signal (ABS) system between Control Point...

77 FR 40700 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0053. Applicant: Alabama and Tennessee River Railway LLC, Mr. Jason Scott, Vice President Signals & Communications...

78 FR 37656 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-21

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... of a signal system. FRA assigned the petition Docket Number FRA-2013-0059. Applicant: Long Island... approval of the proposed modification of the railroad signal interlocking systems at DB & Cabin M...

78 FR 12823 - Notice of Joint Application for Approval of Discontinuance or Modification of a Railroad Signal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-25

... of Joint Application for Approval of Discontinuance or Modification of a Railroad Signal System In... Administration (FRA) seeking approval for the discontinuance or modification of a signal system. FRA assigned the.... David B. Olson, Chief Engineer Communication and Signals, 500 Water Street, Speed Code J-350...

76 FR 55622 - Systems for Telephonic Notification of Unsafe Conditions at Highway-Rail and Pathway Grade Crossings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-08

... Highway-Rail and Pathway Grade Crossings AGENCY: Federal Railroad Administration (FRA), Department of... unsafe conditions at highway-rail and pathway grade crossings. FRA is announcing a public hearing to... and pathway grade crossings. See 76 FR 11992-12012 (March 4, 2011). Interested parties are invited to...

76 FR 41859 - Waiver Petition Docket Numbers FRA-2011-0002, CSX Transportation Railroad, and FRA-2004-17565...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-15

... FR 10087) announcing the CSX Transportation Railroad's (CSXT) request for a waiver to operate RailRunner equipment in RailRunner only operations; operate RailRunner equipment commingled with RoadRailer bi-modal equipment; and RailRunner equipment operating behind various conventional railcars. On...

49 CFR 240.103 - Approval of design of individual railroad programs by FRA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Approval of design of individual railroad programs by FRA. 240.103 Section 240.103 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION QUALIFICATION AND CERTIFICATION OF LOCOMOTIVE ENGINEERS Component Elements of the...

77 FR 24760 - Safety Advisory 2012-02; Restricted Speed

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-25

... recommend that FRA: \\1\\ Available online at NTSB's Web site: http://www.ntsb.gov/doclib/recletters/2011/R-11... bulletins on [FRA's Web site], advise all railroads of the occurrences of the following five recent rear end... intermodal train. The intermodal train was following the rock train, and had passed a dark (non-illuminated...

Disrupting a key hydrophobic pair in the oligomerization interface of the actinoporins impairs their pore‐forming activity

PubMed Central

Mesa‐Galloso, Haydeé; Delgado‐Magnero, Karelia H.; Cabezas, Sheila; López‐Castilla, Aracelys; Hernández‐González, Jorge E.; Pedrera, Lohans; Alvarez, Carlos; Peter Tieleman, D.; García‐Sáez, Ana J.; Lanio, Maria E.; Valiente, Pedro A.

2017-01-01

Abstract Crystallographic data of the dimeric and octameric forms of fragaceatoxin C (FraC) suggested the key role of a small hydrophobic protein–protein interaction surface for actinoporins oligomerization and pore formation in membranes. However, site‐directed mutagenesis studies supporting this hypothesis for others actinoporins are still lacking. Here, we demonstrate that disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII), and sticholysin II (StII) impairs the pore formation activity of these proteins. Our results allow for the extension of the importance of FraC protein–protein interactions in the stabilization of the oligomeric intermediates of StII and EqtII pointing out that all of these proteins follow a similar pathway of membrane disruption. These findings support the hybrid pore proposal as the universal model of actinoporins pore formation. Moreover, we reinforce the relevance of dimer formation, which appears to be a functional intermediate in the assembly pathway of some different pore‐forming proteins. PMID:28000294

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

PubMed

Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

2012-04-01

The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

Thromboembolism and bleeding risk scores and predictors of cardiac death in a population with atrial fibrillation.

PubMed

Silva, Rose Mary Ferreira Lisboa da; Silva, Pollyana Ardavicius E; Lima, Marcos Correia; Sant'Anna, Lívia Tanure; Silva, Túlio Corrêa; Moreira, Pedro Henrique Vilela; Gandra, Robert Moreira; Cavalcanti, Túlio Ramos; Mourão, Plínio Henrique Vaz

2017-07-01

Atrial fibrillation (AF) is a common arrhythmia, with risk of systemic embolism and death. It presents rheumatic etiology in up to 32% of developing countries, whose anticoagulation and evolution data are scarce. to determine the predictors of cardiac death considering the clinical profile, thromboembolism and bleeding scores of patients with AF of a single center, with high prevalence of rheumatic heart disease. 302 patients with AF were studied, mean age 58.1 years; 161 women; 96 pts with rheumatic etiology. Patients underwent clinical and laboratory evaluation, measurement of risk scores and the mean follow-up of 12.8 months. 174 were using warfarin. The averages of the HAS-BLED and ATRIA scores were 1.4 and 1.2, respectively. Percent time in therapeutic range of international normalized ratio was 45.8%. Thirty patients (9.9%) had cardiac death and 41 had some type of bleeding due to warfarin. By univariate analysis, there was statistical significance between cardiac death and permanent AF, blood pressure, systolic dysfunction, R2CHADS2, CCS, EHRA and HAS-BLED. There was no association with valvular AF. By multivariate analysis, systemic arterial and pulmonary artery pressures, classification CCS and systolic dysfunction showed statistical significance. There was no association between cardiac death and valvular AF. Independent predictors of cardiac death were low measures of blood pressure, higher score CCS classification and the presence of systolic ventricular dysfunction. A fibrilação atrial (FA) é uma arritmia comum, com risco de embolia sistêmica e morte. Apresenta etiologia reumática em até 32% dos países em desenvolvimento, cujos dados de anticoagulação e evolução são escassos. Verificar as variáveis preditoras de morte cardíaca (MC) conforme o perfil clínico, os escores de tromboembolismo e de sangramento dos pacientes com FA de uma única instituição universitária, com alta prevalência de cardiopatia reumática. Foram estudados 302 pts com FA, média de idade 58,1 anos; 161 mulheres; 96 pts com etiologia reumática. Os pts foram submetidos à avaliação clínica e laboratorial, ao cálculo dos escores de risco e ao seguimento clínico médio de 12,8 meses. 174 pts estavam em uso de varfarina. As médias dos escores HAS-BLED e ATRIA foram de 1,4 e de 1,2, respectivamente. O cálculo da fração dos valores da razão normalizada internacional dentro do intervalo terapêutico foi de 45,8%. Houve MC em 30 pts (9,9%) e 41 apresentaram algum tipo de hemorragia em decorrência do uso de varfarina. Pela análise univariada, houve significância estatística entre MC e FA permanente, pressões arteriais, disfunção sistólica, R2CHADS2, CCS, EHRA e HAS-BLED. Não houve associação com FA valvar. Por meio da análise multivariada, a pressão arterial sistêmica e da artéria pulmonar, a classificação CCS e a disfunção sistólica apresentavam significância estatística. Não houve associação entre MC e FA valvar. Os preditores independentes de MC foram medidas baixas de pressão arterial, escores mais elevados da classificação CCS e a presença de disfunção ventricular sistólica.

Anthropogenic impact in the Santa Maria di Leuca cold-water coral province (Mediterranean Sea): Observations and conservation straits

NASA Astrophysics Data System (ADS)

D'Onghia, G.; Calculli, C.; Capezzuto, F.; Carlucci, R.; Carluccio, A.; Grehan, A.; Indennidate, A.; Maiorano, P.; Mastrototaro, F.; Pollice, A.; Russo, T.; Savini, A.; Sion, L.; Tursi, A.

2017-11-01

The Santa Maria di Leuca (SML) cold-water coral (CWC) province is a proposed priority conservation area according to several conservation initiatives in the Mediterranean Sea. Part of it is a Fisheries Restricted Area (FRA). Anthropogenic impacts due to fishing on this FRA were investigated using a towed camera system during 2005. The geographic distribution of fishing effort in the SML CWC province was examined through an observers' program of longline and trawl fishing activities during 2009 and 2010 and Vessel Monitoring by satellite System (VMS) data from 2008 to 2013. Using the video system, it was possible to observe evidence of impacts in the FRA due to longlines, proved by remains of lines on the bottoms and/or entangled in corals, and those due to trawl nets, proved by trawl door scars on the bottom. The application of Generalized Liner Models indicates that the impacts due to longline were significantly related to a geographic site characterized by carbonate mounds while those from trawl net were significantly related to the soft bottoms, consisting of bioturbated fine-grained sediments. The presence of waste of various types was also observed in the FRA; plastic was the most widespread waste and was significantly related to a macrohabitat characterized by the presence of corals. The geographic distribution of fishing effort for each type of fishing were rather superimposed in the two years of the observers' program and six years of VMS data with a significantly greater fishing effort outside the FRA than inside this area. The trawlers generally fished on the muddy bottoms of the upper and middle slope within the SML CWC province and near and inside the northward limit of the FRA. The longliners fished mainly on the shelf in north and off the FRA. The coral by-catch was only recorded during 2009 in 26% of the trawl hauls. No coral by-catch was recorded from longlining in either year. The catches from longlining mainly consisted of Chelidonichthys lucerna, Merluccius merluccius and Conger conger while those from trawling mostly consisted of Aristeus antennatus, Aristaeomorpha foliacea and M. merluccius. The information collected during the observers' program and VMS data indicated greater impact due to trawling than longlining. The conservation and effective management of this vulnerable marine ecosystem remain difficult.

A Tracking Study Regarding Issues Related to Recruitment of Enlisted Personnel for the Reserve Components. Wave I. Fall 1978. Volume 2.

DTIC Science & Technology

1979-05-01

with a positive propensity to enlist. 6 P STRISU TION, AVAILABILITY OF ABSTRACT 21 Af T ef& Uf T CLASSIFICATION TJUNCLASSIFIED/UNLIMITED 0 SAME AS RPT...8217, C’ C’ CO C- C S CU’ r-I C M (n (3)4-1 9 1 4-2 ) rIIo4LO 1 UIU 00 SD M Ir5 C a) 4-0 0 4- 4$m4~~ Eu~ a a) Czt 8r ~Q(~)+ ~ ~ 0~ x Cr-a) Cd -) 4-) >a

Autologous Bone Marrow Mononuclear Cell Therapy is Safe and Promotes Amputation Free Survival in Patients with Critical Limb Ischemia

PubMed Central

Murphy, Michael P.; Lawson, Jeffrey H.; Rapp, Brian M.; Dalsing, Michael C.; Klein, Janet; Wilson, Michael G.; Hutchins, Gary D.; March, Keith L.

2011-01-01

Objective The purpose of this phase I open label non-randomized trial was to assess the safety and efficacy of autologous bone marrow mononuclear cell (ABMNC) therapy in promoting amputation free survival (AFS) in patients with critical limb ischemia (CLI). Methods Between September 2005 and March 2009 twenty-nine patients (30 limbs), with a median age of 66 (range 23–84) (14 male,15 female) with CLI were enrolled . Twentyone limbs presented with rest pain (RP), six with RP and ulceration, and three with ulcer only. All patients were not candidates for surgical bypass due to absence of a patent artery below the knee and/or endovascular approaches to improving perfusion was not possible as determined by an independent vascular surgeon. Patients were treated with an average dose of 1.7 ± 0.7 × 109 ABMNC injected intramuscularly in the index limb distal to the anterior tibial tuberosity. The primary safety endpoint was accumulation of serious adverse events and the primary efficacy endpoint was AFS at one year. Secondary endpoints at 12 weeks post-treatment were changes in first toe pressure (FTP), toe-brachial index (TBI), ankle-brachial index (ABI), and transcutaneous oxygen measurements (TcPO2). Perfusion of the index limb was measured with PET-CT with intra-arterial infusion of H2O15. Rest pain (RP), using a 10-cm visual analog scale, quality of life using the VascuQuol questionnaire, and ulcer healing were assessed at each follow-up interval. Subpopulations of endothelial progenitor cells were quantified prior to ABMNC administration using immunocytochemistry and fluorescent activated cell sorting. Results There were two serious adverse events however there no procedure related deaths. Amputation-free survival at one-year was 86.3%. There was a significant increase in FTP (10.2+ 6.2 mmHg, P=.02) and TBI (0.10± 0.05, P=.02) and a trend in improvement in ABI (0.08±0.04, P=.73). Perfusion Index by PET-CT H2O15 increased by 19.3 ± 3.1 and RP decreased significantly by 2.2 ± 0.6 cm. (P=.02). The VascuQol questionnaire demonstrated significant improvement in QOL and three of 9 ulcers (33%) healed completely. KDR+ but not CD34+ or CD133+ subpopulations of ABMNC were associated with improvement in limb perfusion. Conclusion This phase I study has demonstrated safety and the AFS rates suggest efficacy of ABMNC in promoting limb salvage in “no option” CLI. Based on these results we plan to test the concept that ABMNCs improve AFS at one year in a phase III randomized, double-blinded multicenter trial. PMID:21514773

49 CFR 225.37 - Magnetic media transfer and electronic submission.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Form (Form FRA F 6180.99); and (3) A notarized hard copy of the Railroad Injury and Illness Summary....99) which is submitted to an FRA-designated computer; and (2) A notarized hard copy of the Railroad... reporting data for the reports identified in paragraph (a) of this section in a year-to-date file format as...

78 FR 77787 - Notice of Joint Application for Approval of Discontinuance or Modification of a Railroad Signal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... written communications concerning the petition, is available for review online at www.regulations.gov and... proceedings by submitting written views, data, or comments. FRA does not anticipate scheduling a public... interested party desires an opportunity for oral comment, they should notify FRA, in writing, before the end...

49 CFR 216.11 - Special notice for repairs-railroad freight car.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight Car...

49 CFR 216.11 - Special notice for repairs-railroad freight car.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight Car...

49 CFR 216.11 - Special notice for repairs-railroad freight car.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight Car...

49 CFR 216.11 - Special notice for repairs-railroad freight car.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight Car...

49 CFR 216.11 - Special notice for repairs-railroad freight car.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Special notice for repairs-railroad freight car...—railroad freight car. (a) When an FRA Motive Power and Equipment Inspector or a State Equipment Inspector determines that a railroad freight car is not in conformity with the requirements of the FRA Freight Car...

78 FR 9107 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... Glazing Standards-- Locomotives, Passenger Cars and Cabooses). FRA assigned the petition Docket Number FRA... requirements set forth in 49 CFR part 223 for one locomotive, one passenger car, and three cabooses--all of... electric 660 HP, was built in 1943 as U.S. Navy 7135. Passenger Coach KJR 1154 was built in the 1920s for...

75 FR 71487 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-23

... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of a signal system, as detailed below. Docket Number FRA-2010-0159 Applicant: BNSF Railway, Mr. James LeVere, AVP Signals, BNSF Railway...

77 FR 31429 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA-2012-0046... discontinuance of an automatic block signal (ABS) system and a traffic control signal (TCS) system on the...

76 FR 34801 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-14

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... the discontinuance or modification of a signal system. FRA assigned the petition Docket Number FRA... decrease of limits consists of moving the 2S signal on the siding south to the clearance point of the No...

77 FR 76597 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... fleet to the age exploration M7 waiver. FRA assigned the petition Docket Number FRA-2004-17099. MNR is...). The MNR M7 fleet is currently undergoing age exploration tests. The MNR M7 fleet is averaging 68,000... only those components not yet captured by the KB-CT1 (M7) age exploration testing in support of this...

Managing wildland fire risk in Florida

Treesearch

J. Brenner; D. Carlton; S. McLellan; A. Dozier; T. Spencer; D. Buckley; A. Ralowicz

2010-01-01

Florida’s Wildland Fire Risk Assessment (FRA), which was completed in 2002, is a statewide effort to develop a comprehensive suite of standardized spatial data layers developed to support implementation of a statewide fuels management strategy. By maintaining focus on fire and fuel dynamics for use with scientifically credible local to statewide applications, the FRA...

78 FR 16358 - Safety Advisory 2013-02; Low-Speed, Wheel-Climb Derailments of Passenger Equipment With “Stiff...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-14

..., Staff Director, Motive Power and Equipment Division, Office of Railroad Safety, FRA, 1200 New Jersey Avenue SE., Washington, DC 20590, telephone (202) 493-6322; or Anna Nassif Winkle, Trial Attorney, Office... studies conducted by the equipment manufacturer and FRA using computer modeling indicate that an uneven...

75 FR 74132 - Notice of Intent To Grant Buy America Waiver to Northern New England Passenger Rail Authority To...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Notice of Intent To Grant Buy America... Department of Transportation (DOT). ACTION: Notice of intent to grant Buy America waiver. SUMMARY: FRA is... Authority's (NNEPRA) waiver request from FRA's Buy America requirement, 49 U.S.C. 24405(a), for the purchase...

Intraoperative Inducibility of Atrial Fibrillation Does Not Predict Early Postoperative Atrial Fibrillation.

PubMed

Lanters, Eva A H; Teuwen, Christophe P; Yaksh, Ameeta; Kik, Charles; van der Does, Lisette J M E; Mouws, Elisabeth M J P; Knops, Paul; van Groningen, Nicole J; Hokken, Thijmen; Bogers, Ad J J C; de Groot, Natasja M S

2018-03-10

Early postoperative atrial fibrillation (EPoAF) is associated with thromboembolic events, prolonged hospitalization, and development of late PoAF (LPoAF). It is, however, unknown if EPoAF can be predicted by intraoperative AF inducibility. The aims of this study are therefore to explore (1) the value of intraoperative inducibility of AF for development of both EPoAF and LPoAF and (2) the predictive value of de novo EPoAF for recurrence of LPoAF. Patients (N=496, 75% male) undergoing cardiothoracic surgery for coronary and/or valvular heart disease were included. AF induction was attempted by atrial pacing, before extracorporeal circulation. All patients were on continuous rhythm monitoring until discharge to detect EPoAF. During a follow-up period of 2 years, LPoAF was detected by ECGs and Holter recordings. Sustained AF was inducible in 56% of patients. There was no difference in patients with or without AF before surgery ( P =0.159), or between different types of surgery ( P =0.687). In patients without a history of AF, incidence of EPoAF and LPoAF was 37% and 2%, respectively. EPoAF recurred in 58% patients with preoperative AF, 53% developed LPoAF. There were no correlations between intraoperative inducibility and EPoAF or LPoAF ( P >0.05). EPoAF was not correlated with LPoAF in patients without a history of AF ( P =0.116), in contrast to patients with AF before surgery ( P <0.001). Intraoperative AF inducibility does not predict development of either EPoAF or LPoAF. In patients with AF before surgery, EPoAF is correlated with LPoAF recurrences. This correlation is absent in patients without AF before surgery. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Characterization of Cd translocation and accumulation in 19 maize cultivars grown on Cd-contaminated soil: implication of maize cultivar selection for minimal risk to human health and for phytoremediation.

PubMed

Wang, Aiyun; Wang, Minyan; Liao, Qi; He, Xiquan

2016-03-01

Maize (Zea mays) has low Cd accumulation in grains and a high biomass compared to other crops. The capacities for Cd accumulation in different maize cultivars are, however, not fully understood. To reduce human health risk from maize grown in Cd-contaminated soil and to provide promising maize cultivars for the phytoremediation of Cd-polluted soil, a field experiment was conducted to screen low-Cd- and high-Cd-accumulation maize cultivars by evaluating the yield, Cd uptake, translocation, and accumulation differences among 19 maize cultivars. There were differences in straw dry weight (DW), root DW, and yield among the 19 cultivars. The cultivars Yudan19, Zhengda999, and Xianyu508 had a higher production compared to that of the other cultivars. The Cd concentrations in the roots were much higher than those in the straws and grains in all cultivars. The Cd accumulation factors (AFS) decreased in the order of accumulation factors in root (AFrs) > accumulation factors in straw (AFss) > accumulation factors in grain (AFgs). The Cd translocation factors (TFs) from root to straw (TFrs) were significantly (p < 0.05) larger than those from straw to grain (TFsg) among all of the cultivars. The TFs for all of the cultivars was less than 1, and the lowest TFsg (0.23) was found in cultivar Xiangyongdan3. The correlation analysis indicated that Cd concentrations in straws showed a significant (p < 0.01) as well as positive correlation with TFrs while a negative correlation with TFsg (p < 0.01). Moreover, Cd accumulation in different tissues decreased in the order straw > grain > root. Among the 19 maize cultivars, Jixiang2118 and Kangnong18 accumulated the highest Cd amount in the aboveground tissues, and the corresponding values were 7,206.51 and 6,598.68 mg hm(-2), respectively. A hierarchical cluster analysis based on the Cd concentrations in grains and straws classified the 19 maize cultivars into four and two groups for a 0.4 minimum distance between clusters, respectively. Yudan19, Zhengda999, and Xianyu508 can be classified into one group in which low Cd in grains meeting the Cd tolerance limit in foods set by China National Standard, suggesting that those cultivars are safety for food and human health. However, Jixiang2118 and Kangnong18 can be classified as another group with potential application for phytoremediation in slightly or moderately Cd-polluted soil because of the high Cd accumulation in the aboveground tissues.

Protein deficiency and intestinal nematode infection in pregnant mice differentially impact fetal growth through specific stress hormones, growth factors, and cytokines.

PubMed

Starr, Lisa M; Scott, Marilyn E; Koski, Kristine G

2015-01-01

Protein deficiency (PD) and intestinal nematode infections commonly co-occur during pregnancy and impair fetal growth, but the complex network of signals has not been explored. Our objective was to assess those stress hormones, growth factors, and cytokines affected by maternal PD and nematode infection and associated with fetal growth. Using a 2 × 2 factorial design, CD-1 mice, fed protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isoenergetic diets, were either uninfected or infected every 5 d with Heligmosomoides bakeri, beginning on gestational day (GD) 5. Biomarker concentrations were measured on GD 18 in maternal serum (m), fetal serum (f), and amniotic fluid (af) by using Luminex. Maternal PD lowered fetal body mass (PS/uninfected 1.25 ± 0.02 g, PS/infected 1.19 ± 0.02 g vs. PD/uninfected 1.11 ± 0.02 g, PD/infected 0.97 ± 0.02 g; P = 0.02), fetal lung (P = 0.005), and liver (P = 0.003) but not brain mass, whereas maternal infection lowered fetal length (PS/uninfected 2.28 ± 0.02 cm, PD/uninfected 2.27 ± 0.03 cm vs. PS/infected 2.21 ± 0.03 cm, PD/infected 2.11 ± 0.02 cm; P = 0.05) and kidney mass (P = 0.04). PD elevated stress hormones (m-adrenocortiotropic hormone, f-corticosterone, af-corticosterone) and reduced insulin-like growth factor 1 in all compartments (P ≤ 0.01), but these were unassociated with fetal mass or length. Fetal mass was positively associated with f-leptin (R(2) = 0.71, P = 0.0001) and negatively with fetal cytokines [tumor necrosis factor-α: R(2) = 0.62, P = 0.001; interleukin-4 (IL-4): R(2) = 0.63, P = 0.0004]. In contrast, maternal infection lowered f-prolactin (P = 0.02) that was positively associated with fetal length (R(2) = 0.43; P = 0.03); no other biomarker was affected by infection. Regression analyses showed associations between organ growth, cytokines, and growth factors: 1) thymus, spleen, heart, and brain with m-IL-10; 2) brain and kidney with f-vascular endothelial growth factor, af-monocyte chemotactic protein 1, af-interferon-γ, and af-eotaxin; and 3) liver and lung with f-leptin and af-corticosterone (all P ≤ 0.02). PD and nematode infection impaired fetal mass and linear growth, respectively. Fetal mass, length, and individual organ masses were regulated by different hormones, growth factors, and cytokines. © 2015 American Society for Nutrition.

A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae.

PubMed

Foster, Andrew W; Dainty, Samantha J; Patterson, Carl J; Pohl, Ehmke; Blackburn, Hannah; Wilson, Clare; Hess, Corinna R; Rutherford, Julian C; Quaranta, Laura; Corran, Andy; Robinson, Nigel J

2014-07-01

The extreme resistance of Saccharomyces cerevisiae to copper is overcome by 2-(6-benzyl-2-pyridyl)quinazoline (BPQ), providing a chemical-biology tool which has been exploited in two lines of discovery. First, BPQ is shown to form a red (BPQ)2 Cu(I) complex and promote Ctr1-independent copper-accumulation in whole cells and in mitochondria isolated from treated cells. Multiple phenotypes, including loss of aconitase activity, are consistent with copper-BPQ mediated damage to mitochondrial iron-sulphur clusters. Thus, a biochemical basis of copper-toxicity in S. cerevisiae is analogous to other organisms. Second, iron regulons controlled by Aft1/2, Cth2 and Yap5 that respond to mitochondrial iron-sulphur cluster status are modulated by copper-BPQ causing iron hyper-accumulation via upregulated iron-import. Comparison of copper-BPQ treated, untreated and copper-only treated wild-type and fra2Δ by RNA-seq has uncovered a new candidate Aft1 target-gene (LSO1) and paralogous non-target (LSO2), plus nine putative Cth2 target-transcripts. Two lines of evidence confirm that Fra2 dominates basal repression of the Aft1/2 regulons in iron-replete cultures. Fra2-independent control of these regulons is also observed but CTH2 itself appears to be atypically Fra2-dependent. However, control of Cth2-target transcripts which is independent of CTH2 transcript abundance or of Fra2, is also quantified. Use of copper-BPQ supports a substantial contribution of metabolite repression to iron-regulation. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae

PubMed Central

Foster, Andrew W; Dainty, Samantha J; Patterson, Carl J; Pohl, Ehmke; Blackburn, Hannah; Wilson, Clare; Hess, Corinna R; Rutherford, Julian C; Quaranta, Laura; Corran, Andy; Robinson, Nigel J

2014-01-01

The extreme resistance of Saccharomyces cerevisiae to copper is overcome by 2-(6-benzyl-2-pyridyl)quinazoline (BPQ), providing a chemical-biology tool which has been exploited in two lines of discovery. First, BPQ is shown to form a red (BPQ)2Cu(I) complex and promote Ctr1-independent copper-accumulation in whole cells and in mitochondria isolated from treated cells. Multiple phenotypes, including loss of aconitase activity, are consistent with copper-BPQ mediated damage to mitochondrial iron–sulphur clusters. Thus, a biochemical basis of copper-toxicity in S. cerevisiae is analogous to other organisms. Second, iron regulons controlled by Aft1/2, Cth2 and Yap5 that respond to mitochondrial iron–sulphur cluster status are modulated by copper-BPQ causing iron hyper-accumulation via upregulated iron-import. Comparison of copper-BPQ treated, untreated and copper-only treated wild-type and fra2Δ by RNA-seq has uncovered a new candidate Aft1 target-gene (LSO1) and paralogous non-target (LSO2), plus nine putative Cth2 target-transcripts. Two lines of evidence confirm that Fra2 dominates basal repression of the Aft1/2 regulons in iron-replete cultures. Fra2-independent control of these regulons is also observed but CTH2 itself appears to be atypically Fra2-dependent. However, control of Cth2-target transcripts which is independent of CTH2 transcript abundance or of Fra2, is also quantified. Use of copper-BPQ supports a substantial contribution of metabolite repression to iron-regulation. PMID:24895027

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome

PubMed Central

Fung, Lawrence K.; Quintin, Eve-Marie; Haas, Brian W.

2013-01-01

Purpose of review The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Recent findings Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive–behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well – microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Summary Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene–brain–behavior links occurring in neurodevelopmental disorders. PMID:22395002

Florida Center for Reading Research (FCRR) Reading Assessment (FRA): Kindergarten to Grade 2. Technical Manual

ERIC Educational Resources Information Center

Foorman, Barbara R.; Petscher, Yaacov; Schatschneider, Chris

2015-01-01

The grades K-2 Florida Center for Reading Research (FCRR) Reading Assessment (FRA) consists of computer-adaptive alphabetic and oral language screening tasks that provide a Probability of Literacy Success (PLS) linked to grade-level performance (i.e., the 40th percentile) on the word reading (in kindergarten) or reading comprehension (in grades…

77 FR 35106 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... 104-13, Sec. 2, 109 Stat. 163 (1995) (codified as revised at 44 U.S.C. 3501-3520), and its.... 44 U.S.C. 3506(c)(2)(A); 5 CFR 1320.8(d)(1), 1320.10(e)(1), 1320.12(a). Specifically, FRA invites... functions, including whether the activities will have practical utility; (ii) the accuracy of FRA's...

78 FR 77787 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... January 1, 2014, and ending before April 1, 2014. A copy of the petition, as well as any written... written views, data, or comments. FRA does not anticipate scheduling a public hearing in connection with... opportunity for oral comment, they should notify FRA, in writing, before the end of the comment period and...

78 FR 20169 - Notice of Availability of an Environmental Assessment for the Proposed Hudson Yards Concrete...

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2013-04-03

... disasters. Amtrak anticipates constructing the proposed Project using Federal funding and, as the proposed...-2788; Phone (212) 275-6975. The EA is also available for review on the FRA Web site at http://www.fra... address future disasters in the NEC. Construction of the Project is proposed at this time because a real...

Chapter 7: Selecting tree species for reforestation of Appalachian mined lands

Treesearch

V. Davis; J.A. Burger; R. Rathfon; C.E. Zipper

2017-01-01

The Forestry Reclamation Approach (FRA) is a method for reclaiming coal-mined land to forested postmining land uses under the federal Surface Mining Control and Reclamation Act of 1977 (SMCRA) (Chapter 2, this volume). Step 4 of the FRA is to plant native trees for commercial timber value, wildlife habitat, soil stability, watershed protection, and other environmental...

Florida Center for Reading Research (FCRR) Reading Assessment (FRA): Grades 3 through 12. Technical Manual

ERIC Educational Resources Information Center

Foorman, Barbara R.; Petscher, Yaacov; Schatschneider, Chris

2015-01-01

The Florida Center for Reading Research (FCRR) Reading Assessment (FRA) consists of computer-adaptive reading comprehension and oral language screening tasks that provide measures to track growth over time, as well as a Probability of Literacy Success (PLS) linked to grade-level performance (i.e., the 50th percentile) on the reading comprehension…

49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

Code of Federal Regulations, 2012 CFR

2012-10-01

...) address of the Regional Administrator for Region 1 is: [email protected]gov. (2) Region 2 consists of....dot.gov. (3) Region 3 consists of Kentucky, Tennessee, North Carolina, South Carolina, Georgia... E-mail address of the Regional Administrator for Region 3 is: [email protected]gov. (4) Region 4...

49 CFR Appendix C to Part 241 - Geographical Boundaries of FRA's Regions and Addresses of FRA's Regional Headquarters

Code of Federal Regulations, 2011 CFR

2011-10-01

...) address of the Regional Administrator for Region 1 is: [email protected]gov. (2) Region 2 consists of....dot.gov. (3) Region 3 consists of Kentucky, Tennessee, North Carolina, South Carolina, Georgia... E-mail address of the Regional Administrator for Region 3 is: [email protected]gov. (4) Region 4...

77 FR 37737 - Environmental Impact Statement for the Northeast Corridor Between Washington, DC, New York, NY...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-22

... issuing this Notice of Intent (Notice) to advise the public of the preparation of a Tier 1 Environmental... Investment Plan (PRCIP). A PRCIP provides the data necessary to support an FRA decision to fund and implement... existing NEC. FRA is issuing this Notice to alert the public and agencies about the preparation of the Tier...

The combined use of analytical tools for exploring tetanus toxin and tetanus toxoid structures.

PubMed

Bayart, Caroline; Peronin, Sébastien; Jean, Elisa; Paladino, Joseph; Talaga, Philippe; Borgne, Marc Le

2017-06-01

Aldehyde detoxification is a process used to convert toxin into toxoid for vaccine applications. In the case of tetanus toxin (TT), formaldehyde is used to obtain the tetanus toxoid (TTd), which is used either for the tetanus vaccine or as carrier protein in conjugate vaccines. Several studies have already been conducted to better understand the exact mechanism of this detoxification. Those studies led to the identification of a number of formaldehyde-induced modifications on lab scale TTd samples. To obtain greater insights of the changes induced by formaldehyde, we used three industrial TTd batches to identify repeatable modifications in the detoxification process. Our strategy was to combine seven analytical tools to map these changes. Mass spectrometry (MS), colorimetric test and amino acid analysis (AAA) were used to study modifications on amino acids. SDS-PAGE, asymmetric flow field flow fractionation (AF4), fluorescence spectroscopy and circular dichroism (CD) were used to study formaldehyde modifications on the whole protein structure. We identified 41 formaldehyde-induced modifications across the 1315 amino acid primary sequence of TT. Of these, five modifications on lysine residues were repeatable across TTd batches. Changes in protein conformation were also observed using SDS-PAGE, AF4 and CD techniques. Each analytical tool brought a piece of information regarding formaldehyde induced-modifications, and all together, these methods provided a comprehensive overview of the structural changes that occurred with detoxification. These results could be the first step leading to site-directed TT mutagenesis studies that may enable the production of a non-toxic equivalent protein without using formaldehyde. Copyright © 2017 Elsevier B.V. All rights reserved.

Atrial Arrhythmia in Ageing Spontaneously Hypertensive Rats: Unraveling the Substrate in Hypertension and Ageing

PubMed Central

Lau, Dennis H.; Shipp, Nicholas J.; Kelly, Darren J.; Thanigaimani, Shivshankar; Neo, Melissa; Kuklik, Pawel; Lim, Han S.; Zhang, Yuan; Drury, Karen; Wong, Christopher X.; Chia, Nicholas H.; Brooks, Anthony G.; Dimitri, Hany; Saint, David A.; Brown, Lindsay; Sanders, Prashanthan

2013-01-01

Background Both ageing and hypertension are known risk factors for atrial fibrillation (AF) although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR). Methods SHR were studied at 12 and 15 months of age (n = 8 per group) together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY). Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP), atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. Results Compared to WKY controls, the SHR demonstrated: Higher systolic blood pressure (p<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy (p<0.05), lower atrial ERP (p = 0.008), increased atrial conduction heterogeneity (p = 0.001) and increased atrial interstitial fibrosis (p = 0.006) & CD68-positive macrophages infiltration (p<0.0001). These changes resulted in higher atrial arrhythmia inducibility (p = 0.01) and longer induced AF episodes (p = 0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. Conclusions Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria. PMID:24013508

A GPU-paralleled implementation of an enhanced face recognition algorithm

NASA Astrophysics Data System (ADS)

Chen, Hao; Liu, Xiyang; Shao, Shuai; Zan, Jiguo

2013-03-01

Face recognition algorithm based on compressed sensing and sparse representation is hotly argued in these years. The scheme of this algorithm increases recognition rate as well as anti-noise capability. However, the computational cost is expensive and has become a main restricting factor for real world applications. In this paper, we introduce a GPU-accelerated hybrid variant of face recognition algorithm named parallel face recognition algorithm (pFRA). We describe here how to carry out parallel optimization design to take full advantage of many-core structure of a GPU. The pFRA is tested and compared with several other implementations under different data sample size. Finally, Our pFRA, implemented with NVIDIA GPU and Computer Unified Device Architecture (CUDA) programming model, achieves a significant speedup over the traditional CPU implementations.

Trametinib plus 4-Methylumbelliferone Exhibits Antitumor Effects by ERK Blockade and CD44 Downregulation and Affects PD-1 and PD-L1 in Malignant Pleural Mesothelioma.

PubMed

Cho, Hiroyuki; Matsumoto, Seiji; Fujita, Yoshiko; Kuroda, Ayumi; Menju, Toshi; Sonobe, Makoto; Kondo, Nobuyuki; Torii, Ikuko; Nakano, Takashi; Lara, Primo N; Gandara, David R; Date, Hiroshi; Hasegawa, Seiki

2017-03-01

Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy in which the mitogen-activated protein kinase pathway plays a critical role in the regulation of tumorigenesis. Hyaluronic acid (HA) is a major component of the extracellular matrix, and elevated HA levels with a concurrent increase in malignant properties are associated with MPM. We evaluated the effects of trametinib, a mitogen-activated protein kinase (MEK) inhibitor, and 4-methylumbelliferone (4-MU), an HA synthesis inhibitor, alone and in combination on MPM cells in vitro and in vivo. We studied the effects of trametinib, 4-MU, and their combination on MPM cells by using cell viability assays, Western blot analysis, and a mouse xenograft model. Trametinib and 4-MU exhibited antiproliferative activity in MPM cells. Trametinib blocked MEK-dependent extracellular signal-regulated kinase (ERK) phosphorylation and decreased CD44 expression in a concentration-dependent manner. Trametinib inhibited the expression of Fra-1 (the activator protein 1 [AP1] component), inhibited ERK phosphorylation, and decreased CD44 expression. 4-MU inhibited ERK phosphorylation but not CD44 expression. In a mouse xenograft model, trametinib and 4-MU alone suppressed tumor growth compared with a control. The combination had a greater inhibitory effect than either monotherapy. Immunohistochemical analysis showed that trametinib treatment alone significantly reduced expression of programmed cell death 1 ligand 1. Furthermore, the combination of trametinib and 4-MU resulted in higher expression of programmed cell death 1 and programmed cell death 1 ligand 1 than did the 4-MU treatment alone. Our results suggest that trametinib and 4-MU are promising therapeutic agents in MPM and that further study of the combination is warranted. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Asymmetric flow field-flow fractionation coupled to inductively coupled plasma mass spectrometry for the quantification of quantum dots bioconjugation efficiency.

PubMed

Menéndez-Miranda, Mario; Encinar, Jorge Ruiz; Costa-Fernández, José M; Sanz-Medel, Alfredo

2015-11-27

Hyphenation of asymmetric flow field-flow fractionation (AF4) to an on-line elemental detection (inductively coupled plasma-mass spectrometry, ICP-MS) is proposed as a powerful diagnostic tool for quantum dots bioconjugation studies. In particular, conjugation effectiveness between a "model" monoclonal IgG antibody (Ab) and CdSe/ZnS core-shell Quantum Dots (QDs), surface-coated with an amphiphilic polymer, has been monitored here by such hybrid AF4-ICP-MS technique. Experimental conditions have been optimized searching for a proper separation between the sought bioconjugates from the eventual free reagents excesses employed during the bioconjugation (QDs and antibodies). Composition and pH of the carrier have been found to be critical parameters to ensure an efficient separation while ensuring high species recovery from the AF4 channel. An ICP-MS equipped with a triple quadropole was selected as elemental detector to enable sensitive and reliable simultaneous quantification of the elemental constituents, including sulfur, of the nanoparticulated species and the antibody. The hyphenated technique used provided nanoparticle size-based separation, elemental detection, and composition analysis capabilities that turned out to be instrumental in order to investigate in depth the Ab-QDs bioconjugation process. Moreover, the analytical strategy here proposed allowed us not only to clearly identify the bioconjugation reaction products but also to quantify nanoparticle:antibodies bioconjugation efficiency. This is a key issue in future development of analytical and bioanalytical photoluminescent QDs applications. Copyright © 2015 Elsevier B.V. All rights reserved.

78 FR 21705 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

... certain provisions of the Federal hours of service laws contained at 49 U.S.C. 21103(a)(4). FRA assigned the petition Docket Number FRA- 2013-0019. In its petition, OAR seeks relief from 49 U.S.C. 21103(a)(4... a 12-hour cycle. The typical duty tour is from 5 a.m. to 5 p.m., 7 days per week, with an occasional...

49 CFR Appendix A to Part 211 - Statement of Agency Policy Concerning Waivers Related to Shared Use of Trackage or Rights-of-Way...

Code of Federal Regulations, 2011 CFR

2011-10-01

....” 49 U.S.C. 20103(d). Waiver petitions are reviewed by FRA's Railroad Safety Board (the “Safety Board... that the facts are different from those presented or have changed substantially, FRA may revise its... safety issues involved in each specific shared use operation and a voice in shaping the safety...

49 CFR Appendix A to Part 211 - Statement of Agency Policy Concerning Waivers Related to Shared Use of Trackage or Rights-of-Way...

Code of Federal Regulations, 2010 CFR

2010-10-01

....” 49 U.S.C. 20103(d). Waiver petitions are reviewed by FRA's Railroad Safety Board (the “Safety Board... that the facts are different from those presented or have changed substantially, FRA may revise its... safety issues involved in each specific shared use operation and a voice in shaping the safety...

From FRA to RFN, or How the Family Resemblance Approach Can Be Transformed for Science Curriculum Analysis on Nature of Science

ERIC Educational Resources Information Center

Kaya, Ebru; Erduran, Sibel

2016-01-01

The inclusion of Nature of Science (NOS) in the science curriculum has been advocated around the world for several decades. One way of defining NOS is related to the family resemblance approach (FRA). The family resemblance idea was originally described by Wittgenstein. Subsequently, philosophers and educators have applied Wittgenstein's idea to…

77 FR 15108 - Proposed Agency Information Collection Activities; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-14

... Act (FRA) (12 U.S.C. 601-604a); Section 25A of the FRA (12 U.S.C. 611- 631); and Regulation K (12 CFR... Changes in Foreign Investments (Made Pursuant to Regulation K). Agency form number: FR 2064. OMB control... information collection are mandatory (Section 5(c) of the BHC Act (12 U.S.C. 1844(c)); Sections 7 and 13 of...

49 CFR Appendix C to Part 215 - FRA Freight Car Standards Defect Code

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false FRA Freight Car Standards Defect Code C Appendix C... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD FREIGHT CAR SAFETY STANDARDS Pt. 215, App. C Appendix C to... 13/4″. (C)(1) Rim thickness is 11/16″ or less; (2) Rim thickness is 5/8″ or less; (3) Rim thickness...

Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.

PubMed

Woodman, Jessica L; Suh, Min Sung; Zhang, Jianxing; Kondaveeti, Yuvabharath; Burgess, Diane J; White, Bruce A; Prestwich, Glenn D; Kuhn, Liisa T

2015-01-01

Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44(+)/CD24(-/low) human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaP(CMHA)CDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaP(CMHA-AF488) was taken up by CD44(+)/CD24(-) BT-474EMT breast cancer cells within 18 hours. nCaP(CMHA)CDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP. This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

The relationship between headache and religious attendance (the Nord-Trøndelag health study- HUNT)

PubMed Central

2014-01-01

Background Religious belief can be used as a pain coping strategy. Our purpose was to evaluate the relationship between headache and religious activity using prospective data from a large population-based study. Methods This longitudinal cohort study used data from two consecutive surveys in the Nord-Trøndelag Health Survey (HUNT 2 and 3) performed in 1995–1997; and 2006–2008. Among the 51,383 participants aged ≥ 20 years who answered headache questions at baseline, 41,766 were eligible approximately 11 years later. Of these, 25,177 (60%) completed the question in HUNT 3 regarding religious activity. Frequent religious attendees (fRA) (used as a marker of stronger religious belief than average) were defined as those who had been to church/prayer house at least once monthly during the last six months. Results In the multivariate analyses, adjusting for known potential confounders, individuals with headache 1–14 days/month in HUNT 2 were more likely to be fRA 11 years later than headache-free individuals. Migraine at baseline predisposed more strongly to fRA at follow-up (OR = 1.25; 95% CI 1.19-1.40) than did non-migrainous headache (OR = 1.13; 95% 1.04-1.23). The odds of being fRA was 48% increased (OR 1.48; 95% 1.19-1.83) among those with migraine 7–14 days/month at baseline compared to subjects without headache. In contrast, headache status at baseline did not influence the odds of being frequent visitors of concerts, cinema and/or theatre at follow-up 11 years later. Conclusions In this prospective study, headache, in particular migraine, at baseline slightly increased the odds of being fRA 11 years later. PMID:24386923

Analysis of the Arabidopsis IRX9/IRX9-L and IRX14/IRX14-L pairs of glycosyltransferase genes reveals critical contributions to biosynthesis of the hemicellulose glucuronoxylan.

PubMed

Wu, Ai-Min; Hörnblad, Emma; Voxeur, Aline; Gerber, Lorenz; Rihouey, Christophe; Lerouge, Patrice; Marchant, Alan

2010-06-01

The hemicellulose glucuronoxylan (GX) is a major component of plant secondary cell walls. However, our understanding of GX synthesis remains limited. Here, we identify and analyze two new genes from Arabidopsis (Arabidopsis thaliana), IRREGULAR XYLEM9-LIKE (IRX9-L) and IRX14-LIKE (IRX14-L) that encode glycosyltransferase family 43 members proposed to function during xylan backbone elongation. We place IRX9-L and IRX14-L in a genetic framework with six previously described glycosyltransferase genes (IRX9, IRX10, IRX10-L, IRX14, FRAGILE FIBER8 [FRA8], and FRA8 HOMOLOG [F8H]) and investigate their function in GX synthesis. Double-mutant analysis identifies IRX9-L and IRX14-L as functional homologs of IRX9 and IRX14, respectively. Characterization of irx9 irx10 irx14 fra8 and irx9-L irx10-L irx14-L f8h quadruple mutants allows definition of a set of genes comprising IRX9, IRX10, IRX14, and FRA8 that perform the main role in GX synthesis during vegetative development. The IRX9-L, IRX10-L, IRX14-L, and F8H genes are able to partially substitute for their respective homologs and normally perform a minor function. The irx14 irx14-L double mutant virtually lacks xylan, whereas irx9 irx9-L and fra8 f8h double mutants form lowered amounts of GX displaying a greatly reduced degree of backbone polymerization. Our findings reveal two distinct sets of four genes each differentially contributing to GX biosynthesis.

Analysis of the Arabidopsis IRX9/IRX9-L and IRX14/IRX14-L Pairs of Glycosyltransferase Genes Reveals Critical Contributions to Biosynthesis of the Hemicellulose Glucuronoxylan1[C][W

PubMed Central

Wu, Ai-Min; Hörnblad, Emma; Voxeur, Aline; Gerber, Lorenz; Rihouey, Christophe; Lerouge, Patrice; Marchant, Alan

2010-01-01

The hemicellulose glucuronoxylan (GX) is a major component of plant secondary cell walls. However, our understanding of GX synthesis remains limited. Here, we identify and analyze two new genes from Arabidopsis (Arabidopsis thaliana), IRREGULAR XYLEM9-LIKE (IRX9-L) and IRX14-LIKE (IRX14-L) that encode glycosyltransferase family 43 members proposed to function during xylan backbone elongation. We place IRX9-L and IRX14-L in a genetic framework with six previously described glycosyltransferase genes (IRX9, IRX10, IRX10-L, IRX14, FRAGILE FIBER8 [FRA8], and FRA8 HOMOLOG [F8H]) and investigate their function in GX synthesis. Double-mutant analysis identifies IRX9-L and IRX14-L as functional homologs of IRX9 and IRX14, respectively. Characterization of irx9 irx10 irx14 fra8 and irx9-L irx10-L irx14-L f8h quadruple mutants allows definition of a set of genes comprising IRX9, IRX10, IRX14, and FRA8 that perform the main role in GX synthesis during vegetative development. The IRX9-L, IRX10-L, IRX14-L, and F8H genes are able to partially substitute for their respective homologs and normally perform a minor function. The irx14 irx14-L double mutant virtually lacks xylan, whereas irx9 irx9-L and fra8 f8h double mutants form lowered amounts of GX displaying a greatly reduced degree of backbone polymerization. Our findings reveal two distinct sets of four genes each differentially contributing to GX biosynthesis. PMID:20424005

Diamond Nucleation of Surfaces Using Carbon Clusters

DTIC Science & Technology

1993-05-01

8217 den lotafC 0, OAF e ol (*(.Pt 01If CZ.,,C :A 4 C.d,^; flt.0"$ j .n to, thl 0..eftC TO 440?.NqtOn -44sca.’lie’l eon Ofttlo tt 0( tl O Af~tO o0V614...is used to keep the sample in place. The cap is made of either graphite, quartz, or boron nitride depending on the particular experiment. In this...John, P., Alvarez, M.M., Diederich, F., and Whetten, R.L., J. Phys. Chem. in press (1991). 40 44. Zhang, Q.L., 0’ Brien , S.C., Heath, J.R., Liu, Y

Falls risk assessment begins with hello: lessons learned from the use of one home health agency's fall risk tool.

PubMed

Flemming, Patricia J; Ramsay, Katherine

2012-10-01

Identifying older adults at risk for falls is a challenge all home healthcare agencies (HHAs) face. The process of assessing for falls risk begins with the initial home visit. One HHA affiliated with an academic medical center describes its experience in development and use of a Falls Risk Assessment (FRA) tool over a 10-year period. The FRA tool has been modified since initial development to clarify elements of the tool based on research and to reflect changes in the Outcome and Assessment Information Set (OASIS) document. The primary purpose of this article is to share a validated falls risk assessment tool to facilitate identification of fall-related risk factors in the homebound population. A secondary purpose is to share lessons learned by the HHA during the 10 years using the FRA.

Bidirectional Transformation of a Metamorphic Protein between the Water-Soluble and Transmembrane Native States.

PubMed

Tanaka, Koji; Caaveiro, Jose M M; Tsumoto, Kouhei

2015-11-24

The bidirectional transformation of a protein between its native water-soluble and integral transmembrane conformations is demonstrated for FraC, a hemolytic protein of the family of pore-forming toxins. In the presence of biological membranes, the water-soluble conformation of FraC undergoes a remarkable structural reorganization generating cytolytic transmembrane nanopores conducive to cell death. So far, the reverse transformation from the native transmembrane conformation to the native water-soluble conformation has not been reported. We describe the use of detergents with different physicochemical properties to achieve the spontaneous conversion of transmembrane pores of FraC back into the initial water-soluble state. Thermodynamic and kinetic stability data suggest that specific detergents cause an asymmetric change in the energy landscape of the protein, allowing the bidirectional transformation of a membrane protein.

Local spin density in the Cr 7Ni antiferromagnetic molecular ring and 53Cr-NMR

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

Casadei, Cecilia M; Bordonali, L; Furukawa, Yuji

We present 53Cr-NMR spectra collected at low temperature in a single crystal of the heterometallic antiferromagnetic (AF) ring Cr 7Ni in the S = 1/2 ground state with the aim of establishing the distribution of the local electronic moment in the ring. Due to the poor S/N we observed only one signal which is ascribed to three almost equivalent 53Cr nuclei in the ring. The calculated spin density in Cr 7Ni in the ground state, with the applied magnetic field both parallel and perpendicular to the plane of the ring, turns out to be AF staggered with the greatest componentmore » of the local spin {s} for the Cr 3+ ions next to the Ni 2+ ion. The 53Cr-NMR frequency was found to be in good agreement with the local spin density calculated theoretically by assuming a core polarization field of H cp =₋ 11 T/μ B for both orientations, close to the value found previously in Cr 7Cd. Lastly, the observed orientation dependence of the local spin moments is well reproduced by the theoretical calculation and evidences the importance of single-ion and dipolar anisotropies.« less

Quantum dots as contrast agents for endoscopy: mathematical modeling and experimental validation of the optimal excitation wavelength

NASA Astrophysics Data System (ADS)

Roy, Mathieu; DaCosta, Ralph S.; Weersink, Robert; Netchev, George; Davidson, Sean R. H.; Chan, Warren; Wilson, Brian C.

2007-02-01

Our group is investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). Our studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. This work quantitatively evaluates the effect of the excitation wavelength on the SBR, using both experimental measurements and mathematical modeling. Experimental SBR measurements were done by imaging QD solutions placed onto (surface) or embedded in (sub-surface) ex vivo murine tissue samples (brain, kidney, liver, lung), using a polymethylmethacrylate (PMMA) microchannel phantom. The results suggest that the maximum contrast is reached when the excitation wavelength is set at 400+/-20 μm for the surface configuration. For the sub-surface configuration, the optimal excitation wavelength varies with the tissue type and QD emission wavelengths. Our mathematical model, based on an approximation to the diffusion equation, successfully predicts the optimal excitation wavelength for the surface configuration, but needs further modifications to be accurate in the sub-surface configuration.

Chapter 3: Selecting materials for mine soil construction when establishing forests on Appalachian mined lands

Treesearch

Jeff Skousen; Carl Zipper; Jim Burger; Christopher Barton; Patrick. Angel

2017-01-01

The Forestry Reclamation Approach (FRA), a method for reclaiming coal-mined land to forest (Chapter 2, this volume), is based on research, knowledge, and experience of forest soil scientists and reclamation practitioners. Step 1 of the FRA is to create a suitable rooting medium for good tree growth that is no less than 4 feet deep and consists of topsoil, weathered...

Restoring Forests and Associated Ecosystem Services on Appalachian Coal Surface Mines

NASA Astrophysics Data System (ADS)

Zipper, Carl E.; Burger, James A.; Skousen, Jeffrey G.; Angel, Patrick N.; Barton, Christopher D.; Davis, Victor; Franklin, Jennifer A.

2011-05-01

Surface coal mining in Appalachia has caused extensive replacement of forest with non-forested land cover, much of which is unmanaged and unproductive. Although forested ecosystems are valued by society for both marketable products and ecosystem services, forests have not been restored on most Appalachian mined lands because traditional reclamation practices, encouraged by regulatory policies, created conditions poorly suited for reforestation. Reclamation scientists have studied productive forests growing on older mine sites, established forest vegetation experimentally on recent mines, and identified mine reclamation practices that encourage forest vegetation re-establishment. Based on these findings, they developed a Forestry Reclamation Approach (FRA) that can be employed by coal mining firms to restore forest vegetation. Scientists and mine regulators, working collaboratively, have communicated the FRA to the coal industry and to regulatory enforcement personnel. Today, the FRA is used routinely by many coal mining firms, and thousands of mined hectares have been reclaimed to restore productive mine soils and planted with native forest trees. Reclamation of coal mines using the FRA is expected to restore these lands' capabilities to provide forest-based ecosystem services, such as wood production, atmospheric carbon sequestration, wildlife habitat, watershed protection, and water quality protection to a greater extent than conventional reclamation practices.

Lack of association between mutation size and cognitive/behavior deficits in fragile X males: A brief report

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

Fisch, G.S.; Carpenter, N.; Simensen, R.

1996-08-09

Previously, researchers reported molecular-neurobehavioral or molecular-cognitive associations in individuals with fra(X) (fragile X) mutation. However, not all investigators have noted molecular-behavioral relationships. Consequently, we examined prospectively 30 fra(X) males age 3-15 years from four testing sites to determine whether there was a relationship between mutation size and degree of either cognitive or adaptive behavior deficit. To measure cognitive abilities, all individuals were administered the Stanford-Binet (4th edition) IQ test. To evaluate adaptive behavior (DQ) skills, all individuals were assessed using the Vineland Adaptive Behavior Scale. To determine fra(X) status, genomic DNA from all individuals was extracted and digested with EcoRImore » and EagI restriction enzymes. Southern blots were prepared and hybridized with the pE5.1 probe. The Pearson correlation coefficient between full mutation size and composite IQ score revealed a non-significant, near-zero association (r = 0.06; P > .76). The Pearson coefficient between mutation size and DQ also showed a non-significant, near-zero association (r = 0.06; P >.73). We conclude that while fra(X) mutation produces cognitive and behavior deficits in males who inherit the defective gene, there is no relationship between mutation size and degree of deficit. 14 refs., 2 figs.« less

Evaluation of the effects of fasting associated dehydration on maternal NGAL levels and fetal renal artery Doppler parameters.

PubMed

Bayoglu Tekin, Yesim; Guvendag Guven, Emine Seda; Mete Ural, Ulku; Yazici, Zihni Acar; Kirbas, Aynur; Kir Sahin, Figen

2016-01-01

The aim of this study was to evaluate maternal neutrophil gelatinase-asssociated lipocalin (NGAL) levels and fetal renal artery (fRA) Doppler flow indices in pregnant women fasting in Ramadan in respect of dehydration in long hot summer days as a marker of hypoperfusion and early renal injury. A cross-sectional observational study was carried out at a University Hospital. Fasting pregnant women and non-fasting age, gravidity and gestational age-matched women were evaluated for hematologic, blood biochemistry and urine parameters in the first and fourth weeks of the Ramadan. Umbilical artery and fRA Doppler flows were studied in each evaluation. Blood urea nitrogen, potassium and hematocrit levels, blood and urine NGAL levels were significantly higher, and fRA Doppler indices increased in fasting women (p < 0.05) during the second visit in the last week of the Ramadan, while non-fasting women had no significant alterations in each evaluation (p > 0.05). Adequate maternal vascular volume is essential for the maintenance of healthy pregnancy. Fasting during the long and hot summer days leads to fluid deprivation and dehydration which was found to be related to subclinical maternal renal dysfunction and increased fRA Doppler indices.

Mutations in GPR143/OA1 and ABCA4 Inform Interpretations of Short-Wavelength and Near-Infrared Fundus Autofluorescence

PubMed Central

Paavo, Maarjaliis; Zhao, Jin; Kim, Hye Jin; Lee, Winston; Zernant, Jana; Cai, Carolyn; Allikmets, Rando; Tsang, Stephen H.; Sparrow, Janet R.

2018-01-01

Purpose We sought to advance interpretations and quantification of short-wavelength fundus autofluorescence (SW-AF) emitted from bisretinoid lipofuscin and near-infrared autofluoresence (NIR-AF) originating from melanin. Methods Carriers of mutations in X-linked GPR143/OA1, a common form of ocular albinism; patients with confirmed mutations in ABCA4 conferring increased SW-AF; and subjects with healthy eyes were studied. SW-AF (488 nm excitation, 500–680 nm emission) and NIR-AF (excitation 787 nm, emission >830 nm) images were acquired with a confocal scanning laser ophthalmoscope. SW-AF images were analyzed for quantitative autofluoresence (qAF). Analogous methods of image acquisition and analysis were performed in albino and pigmented Abca4−/− mice and wild-type mice. Results Quantitation of SW-AF (qAF), construction of qAF color-coded maps, and examination of NIR-AF images from GPR143/OA1 carriers revealed mosaics in which patches of fundus exhibiting NIR-AF signal had qAF levels within normal limits whereas the hypopigmented areas in the NIR-AF image corresponded to foci of elevated qAF. qAF also was increased in albino versus pigmented mice. Although melanin contributes to fundus infrared reflectance, the latter appeared to be uniform in en face reflectance images of GPR143/OA1-carriers. In patients diagnosed with ABCA4-associated disease, NIR-AF increased in tandem with increased qAF originating in bisretinoid lipofuscin. Similarly in Abca4−/− mice having increased SW-AF, NIR-AF was more pronounced than in wild-type mice. Conclusions These studies corroborate RPE melanin as the major source of NIR-AF but also indicate that bisretinoid lipofuscin, when present at sufficient concentrations, contributes to the NIR-AF signal. Ocular melanin attenuates the SW-AF signal.

Screening for asymptomatic atrial fibrillation while monitoring the blood pressure at home: trial of regular versus irregular pulse for prevention of stroke (TRIPPS 2.0).

PubMed

Wiesel, Joseph; Abraham, Saji; Messineo, Frank C

2013-06-01

Asymptomatic atrial fibrillation (AF) is a common cause of strokes. Physician screening for AF has been recommended. Home screening for AF may increase the likelihood of detecting asymptomatic AF in patients at risk for stroke because of AF. The aim of this study was to assess the feasibility and accuracy of screening for AF when taking home blood pressure (BP) measurements using an automatic AF-detecting BP monitor. Subjects aged >64 years or those with hypertension, diabetes, congestive heart failure, or previous stroke were enrolled by their primary physicians and given the AF-BP monitor and an electrocardiographic event monitor to use at home for 30 days. The AF-BP monitor reading was compared with the electrocardiographic reading to calculate the sensitivity and specificity of the device for detecting AF. A total of 160 subjects were enrolled, with 10 withdrawing, 1 excluded, and 10 with no AF-BP monitor logs or electrocardiographic recordings. Of the 139 subjects included, 14 had known AF. There was a total of 3,316 days with AF-BP monitor readings and electrocardiographic readings. On the basis of the initial daily AF-BP monitor readings, the AF-BP monitor demonstrated sensitivity of 99.2% and specificity of 92.9% for detecting AF. Two subjects with no histories of AF had AF-BP monitor readings of AF that were confirmed by the electrocardiographic monitor. One of these subjects was started on warfarin. In conclusion, home screening for asymptomatic AF while taking BP measurements can be performed accurately. This can be used to detect new AF, allowing treatment with anticoagulation to reduce the future risk for stroke. Copyright © 2013 Elsevier Inc. All rights reserved.

The association between atrial fibrillation and cognitive function in patients with heart failure.

PubMed

Yang, Huifeng; Niu, Weihua; Zang, Xiaoying; Lin, Mei; Zhao, Yue

2017-02-01

Atrial fibrillation (AF) is associated with cognitive impairment in heart failure (HF). The purpose of this study was to examine whether AF independently predicted cognitive function in HF patients after controlling for more demographic, medical and psychological characteristics, and whether the timing of AF onset in relation to HF diagnosis independently contributed to cognitive function in HF patients with AF. A total of 188 hospitalized HF patients (62.8% male, age 66.3±10.6 years) completed cognitive function assessment with the Montreal Cognitive Assessment (MoCA). A history of AF, along with other medical characteristics, was ascertained through a review of participants' medical charts. The timing of AF onset in relation to HF diagnosis was categorized into AF occurring prior to HF diagnosis (i.e. prior AF) and AF developing after HF diagnosis (i.e. incident AF). Altogether 72 participants had a positive diagnostic history of AF. Specifically, 41 had prior AF, and 31 developed AF subsequently. In HF patients, AF was associated with poorer performance on cognitive function after controlling for more confounders (β=-0.112, ΔR 2 =0.010, p=0.046). Among HF patients with AF, incident AF independently predicted poorer cognitive function (β=-0.238, ΔR 2 =0.027, p=0.047). AF independently contributes to cognitive function in HF patients after adjusting for more confounding variables. The timing of AF onset in relation to HF diagnosis independently predicts cognitive function in HF patients with AF. Prospective studies are needed to elucidate possible mechanisms for the association between AF and cognitive function in HF populations.

Notch3 negatively regulates chemoresistance in breast cancers.

PubMed

Gu, Xiaoting; Lu, Chunxiao; He, Dongxu; Lu, Yangfan; Jin, Jian; Liu, Dequan; Ma, Xin

2016-10-14

To define the role of the NOTCH signaling pathway in the development of chemoresistance and the associated epithelial-mesenchymal transition (EMT), we investigated the effect of Notch3 on adriamycin (ADM)-resistant human breast cancer cells (MCF-7/ADM cells). We found that Notch3 was downregulated and involved in the chemoresistance of MCF-7/ADM cells, while forced expression of Notch3 reversed the chemoresistance. Furthermore, fos-related antigen 1 (Fra1) was negatively regulated by Notch3 and was highly expressed in MCF-7/ADM cells. Increased Fra1 activated the EMT process. Finally, Notch3 expression was confirmed in clinically chemoresistant samples of breast cancers from patients receiving anthracycline-based chemotherapy. Low expression of Notch3 was an unfavorable predictor of distant relapse-free survival in ER positive breast cancers. Taken together, our findings demonstrate that the Notch3-Fra1 signaling pathway mediates chemoresistance via the EMT.

Magnetic viscosity phenomena in exchange coupled CoFe /MnIr bilayers

NASA Astrophysics Data System (ADS)

Kim, Dong Young; Kim, C. O.; Tsunoda, M.; Yamaguchi, M.; Yabugami, S.; Takahashi, M.

2007-05-01

The complex permeability spectra were measured in the low (10Hz-1MHz) and microwave (100MHz-9GHz) frequency ranges in CoFe /MnIr bilayers. The low frequency permeability spectra showed the magnetic viscosity effect below the critical antiferromagnet thickness (tcAF), but not at tAFtcAF. The discrepancies between dynamic and quasistatic measurements of the Jc only begin to appear in the vicinity of the tcAF and dominate at tAF

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

PubMed

Steinberg, Benjamin A; Gao, Haiyan; Shrader, Peter; Pieper, Karen; Thomas, Laine; Camm, A John; Ezekowitz, Michael D; Fonarow, Gregg C; Gersh, Bernard J; Goldhaber, Samuel; Haas, Sylvia; Hacke, Werner; Kowey, Peter R; Ansell, Jack; Mahaffey, Kenneth W; Naccarelli, Gerald; Reiffel, James A; Turpie, Alexander; Verheugt, Freek; Piccini, Jonathan P; Kakkar, Ajay; Peterson, Eric D; Fox, Keith A A

2017-12-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment. Demographics, comorbidities, and stroke risk of the patients in the GARFIELD-AF (n=51,270), ORBIT-AF I (n=10,132), and ORBIT-AF II (n=11,602) registries were compared (overall N=73,004 from 35 countries). Stroke prevention therapies were assessed among patients with new-onset AF (≤6 weeks). Patients from GARFIELD-AF were less likely to be white (63% vs 89% for ORBIT-AF I and 86% for ORBIT-AF II) or have coronary artery disease (19% vs 36% and 27%), but had similar stroke risk (85% CHA 2 DS 2 -VASc ≥2 vs 91% and 85%) and lower bleeding risk (11% with HAS-BLED ≥3 vs 24% and 15%). Oral anticoagulant use was 46% and 57% for patients with a CHA 2 DS 2 -VASc=0 and 69% and 87% for CHA 2 DS 2 -VASc ≥2 in GARFIELD-AF and ORBIT-AF II, respectively, but with substantial geographic heterogeneity in use of oral anticoagulant (range: 31%-93% [GARFIELD-AF] and 66%-100% [ORBIT-AF II]). Among patients with new-onset AF, non-vitamin K antagonist oral anticoagulant use increased over time to 43% in 2016 for GARFIELD-AF and 71% for ORBIT-AF II, whereas use of antiplatelet monotherapy decreased from 36% to 17% (GARFIELD-AF) and 18% to 8% (ORBIT-AF I and II). Among new-onset AF patients, non-vitamin K antagonist oral anticoagulant use has increased and antiplatelet monotherapy has decreased. However, anticoagulation is used frequently in low-risk patients and inconsistently in those at high risk of stroke. Significant geographic variability in anticoagulation persists and represents an opportunity for improvement. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Correlations Among Near-Infrared and Short-Wavelength Autofluorescence and Spectral-Domain Optical Coherence Tomography in Recessive Stargardt Disease

PubMed Central

Duncker, Tobias; Marsiglia, Marcela; Lee, Winston; Zernant, Jana; Tsang, Stephen H.; Allikmets, Rando; Greenstein, Vivienne C.; Sparrow, Janet R.

2014-01-01

Purpose. Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in retinal pigment epithelium (RPE) and near-infrared (NIR) AF from melanin. In patients with recessive Stargardt disease (STGD1), we correlated SW-AF and NIR-AF with structural information obtained by spectral-domain optical coherence tomography (SD-OCT). Methods. Twenty-four STGD1 patients (45 eyes; age 8 to 61 years) carrying confirmed disease-associated ABCA4 mutations were studied prospectively. Short-wavelength AF, NIR-AF, and SD-OCT images were acquired. Results. Five phenotypes were identified according to features of the central lesion and extent of fundus change. Central zones of reduced NIR-AF were typically larger than areas of diminished SW-AF and reduced NIR-AF usually approximated areas of ellipsoid zone (EZ) loss identified by SD-OCT (group 1; r, 0.93, P < 0.0001). In patients having a central lesion with overlapping parafoveal rings of increased NIR-AF and SW-AF (group 3), the extent of EZ loss was strongly correlated with the inner diameter of the NIR-AF ring (r, 0.89, P < 0.0001) and the eccentricity of the outer border of the NIR-AF ring was greater than that of the SW-AF ring. Conclusions. Lesion areas were more completely delineated in NIR-AF images than with SW-AF. In most cases, EZ loss was observed only at locations where NIR-AF was reduced or absent, indicating that RPE cell atrophy occurs in advance of photoreceptor cell degeneration. Because SW-AF was often increased within the central area of EZ disruption, degenerating photoreceptor cells may produce lipofuscin at accelerated levels. Consideration is given to mechanisms underlying hyper–NIR-AF in conjunction with increased SW-AF. PMID:25342616

Engineering a horseradish peroxidase C stable to radical attacks by mutating multiple radical coupling sites.

PubMed

Kim, Su Jin; Joo, Jeong Chan; Song, Bong Keun; Yoo, Young Je; Kim, Yong Hwan

2015-04-01

Peroxidases have great potential as industrial biocatalysts. In particular, the oxidative polymerization of phenolic compounds catalyzed by peroxidases has been extensively examined because of the advantage of this method over other conventional chemical methods. However, the industrial application of peroxidases is often limited because of their rapid inactivation by phenoxyl radicals during oxidative polymerization. In this work, we report a novel protein engineering approach to improve the radical stability of horseradish peroxidase isozyme C (HRPC). Phenylalanine residues that are vulnerable to modification by the phenoxyl radicals were identified using mass spectrometry analysis. UV-Vis and CD spectra showed that radical coupling did not change the secondary structure or the active site of HRPC. Four phenylalanine (Phe) residues (F68, F142, F143, and F179) were each mutated to alanine residues to generate single mutants to examine the role of these sites in radical coupling. Despite marginal improvement of radical stability, each single mutant still exhibited rapid radical inactivation. To further reduce inactivation by radical coupling, the four substitution mutations were combined in F68A/F142A/F143A/F179A. This mutant demonstrated dramatic enhancement of radical stability by retaining 41% of its initial activity compared to the wild-type, which was completely inactivated. Structure and sequence alignment revealed that radical-vulnerable Phe residues of HPRC are conserved in homologous peroxidases, which showed the same rapid inactivation tendency as HRPC. Based on our site-directed mutagenesis and biochemical characterization, we have shown that engineering radical-vulnerable residues to eliminate multiple radical coupling can be a good strategy to improve the stability of peroxidases against radical attack. © 2014 Wiley Periodicals, Inc.

Atrial Fibrillation Burden: Moving Beyond Atrial Fibrillation as a Binary Entity: A Scientific Statement From the American Heart Association.

PubMed

Chen, Lin Y; Chung, Mina K; Allen, Larry A; Ezekowitz, Michael; Furie, Karen L; McCabe, Pamela; Noseworthy, Peter A; Perez, Marco V; Turakhia, Mintu P

2018-05-15

Our understanding of the risk factors and complications of atrial fibrillation (AF) is based mostly on studies that have evaluated AF in a binary fashion (present or absent) and have not investigated AF burden. This scientific statement discusses the published literature and knowledge gaps related to methods of defining and measuring AF burden, the relationship of AF burden to cardiovascular and neurological outcomes, and the effect of lifestyle and risk factor modification on AF burden. Many studies examine outcomes by AF burden classified by AF type (paroxysmal versus nonparoxysmal); however, quantitatively, AF burden can be defined by longest duration, number of AF episodes during a monitoring period, and the proportion of time an individual is in AF during a monitoring period (expressed as a percentage). Current guidelines make identical recommendations for anticoagulation regardless of AF pattern or burden; however, a review of recent evidence suggests that higher AF burden is associated with higher risk of stroke. It is unclear whether the risk increases continuously or whether a threshold exists; if a threshold exists, it has not been defined. Higher burden of AF is also associated with higher prevalence and incidence of heart failure and higher risk of mortality, but not necessarily lower quality of life. A structured and comprehensive risk factor management program targeting risk factors, weight loss, and maintenance of a healthy weight appears to be effective in reducing AF burden. Despite this growing understanding of AF burden, research is needed into validation of definitions and measures of AF burden, determination of the threshold of AF burden that results in an increased risk of stroke that warrants anticoagulation, and discovery of the mechanisms underlying the weak temporal correlations of AF and stroke. Moreover, developments in monitoring technologies will likely change the landscape of long-term AF monitoring and could allow better definition of the significance of changes in AF burden over time. © 2018 American Heart Association, Inc.

Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

PubMed Central

Johnson, Timothy D.; Dittgen, Felix; Nichols, Thomas E.; Malzahn, Uwe; Veltkamp, Roland

2017-01-01

Objective Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke. Methods Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke. Results 582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF. Conclusions In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations. PMID:28542605

The role of remote sensing in global forest assessment: A remote sensing background paper for Kotka IV expert consultation; 01.07-05.07.2002, Kotka, Finland

Treesearch

Erkki Tomppo; Raymond L. Czaplewski; Kai Makisara

2002-01-01

The approach of FRA 2000 by FAO was the reliance on the participation of individual countries for both supply and analysis of information. It is hoped that this approach will lead for further capacity building in countries (FRA 2000 -main report). While countries firmly support this approach, it has sometimes been criticised on the basis that country information may be...

Heavy metals and metalloids in the surface sediments of the Xiangjiang River, Hunan, China: distribution, contamination, and ecological risk assessment.

PubMed

Chai, Liyuan; Li, Huan; Yang, Zhihui; Min, Xiaobo; Liao, Qi; Liu, Yi; Men, Shuhui; Yan, Yanan; Xu, Jixin

2017-01-01

Here, we aim to determine the distribution, ecological risk and sources of heavy metals and metalloids in the surface sediments of the Xiangjiang River, Hunan Province, China. Sixty-four surface sediment samples were collected in 16 sites of the Xiangjiang River, and the concentrations of ten heavy metals and metalloids (Mn, Zn, Cr, V, Pb, Cu, As, Ni, Co, and Cd) in the sediment samples were investigated using an inductively coupled plasma mass spectrometer (ICP-MS) and an atomic fluorescence spectrophotometer (AFS), respectively. The results showed that the mean concentrations of the ten heavy metals and metalloids in the sediment samples followed the order Mn > Zn > Cr > V > Pb > Cu > As ≈ Ni >Co > Cd. The geoaccumulation index (I geo ), enrichment factor (EF), modified degree of contamination (mC d ), and potential ecological risk index (RI) revealed that Cd, followed by Pb, Zn, and Cu, caused severely contaminated and posed very highly potential ecological risk in the Xiangjiang River, especially in Shuikoushan of Hengyang, Xiawan of Zhuzhou, and Yijiawan of Xiangtan. The Pearson's correlation coefficient (PCC) analysis, principal component analysis (PCA), and hierarchical cluster analysis (HCA) indicated that the ten heavy metals and metalloids in the sampling sediments of the Xiangjiang River were classified into three groups: (1) Cd, Pb, Zn, and Cu which possibly originated from Shuikoushan, Xiawan, and Yijiawan clustering Pb-Zn mining and smelting industries; (2) Co, V, Ni, Cr, and Al from natural resources; and (3) Mn and As. Therefore, our results suggest that anthropogenic activities, especially mining and smelting, have caused severe contamination of Cd, Pb, Zn, and Cu and posed very high potential ecological risk in the Xiangjiang River.

Global forest cover mapping for the United Nations Food and Agriculture Organization forest resources assessment 2000 program

USGS Publications Warehouse

Zhu, Z.; Waller, E.

2003-01-01

Many countries periodically produce national reports on the status and changes of forest resources, using statistical surveys and spatial mapping of remotely sensed data. At the global level, the Food and Agriculture Organization (FAO) of the United Nations has conducted a Forest Resources Assessment (FRA) program every 10 yr since 1980, producing statistics and analysis that give a global synopsis of forest resources in the world. For the year 2000 of the FRA program (FRA2000), a global forest cover map was produced to provide spatial context to the extensive survey. The forest cover map, produced at the U.S. Geological Survey (USGS) EROS Data Center (EDC), has five classes: closed forest, open or fragmented forest, other wooded land, other land cover, and water. The first two forested classes at the global scale were delineated using combinations of temporal compositing, modified mixture analysis, geographic stratification, and other classification techniques. The remaining three FAO classes were derived primarily from the USGS global land cover characteristics database (Loveland et al. 1999). Validated on the basis of existing reference data sets, the map is estimated to be 77% accurate for the first four classes (no reference data were available for water), and 86% accurate for the forest and nonforest classification. The final map will be published as an insert to the FAO FRA2000 report.

Activation function 2 (AF2) of estrogen receptor-α is required for the atheroprotective action of estradiol but not to accelerate endothelial healing

PubMed Central

Billon-Galés, Audrey; Krust, Andrée; Fontaine, Coralie; Abot, Anne; Flouriot, Gilles; Toutain, Céline; Berges, Hortense; Gadeau, Alain-Pierre; Lenfant, Françoise; Gourdy, Pierre; Chambon, Pierre; Arnal, Jean-François

2011-01-01

17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF20). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF20 to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF20 mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF20 in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF20 LDL-r−/− mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect. PMID:21788522

Green digital signage using nanoparticle embedded narrow-gap field sequential TN-LCDs

NASA Astrophysics Data System (ADS)

Kobayashi, Shunsuke; Shiraishi, Yukihide; Sawai, Hiroya; Toshima, Naoki; Okita, Masaya; Takeuchi, Kiyofumi; Takatsu, Haruyoshi

2012-03-01

We have fabricated field sequential color (FSC)-LCDs using cells and modules of narrow-gap TN-LCDs with and without doping the nanoparticles of PCyD-ZrO2 and AF-SiO2. It is shown that the FSC-LCD exhibits a high optical efficiency of OE=4.5 that is defined as OE=[Luminance]/[W/m2]=(cd/W). This figure may provide us a good reference or to clear the Energy Star Program Version 5-3 that issues a guideline: LCD with 50 inch on the diagonal consumes the energy of 108W. Through this research it is claimed that our FSC=LCD may be a novel green digital signage.

Magnetic ground states in the three O s6 + (5 d2 ) double perovskites B a2M Os O6 (M =Mg ,Zn,and Cd) from Néel order to its suppression

NASA Astrophysics Data System (ADS)

Marjerrison, C. A.; Thompson, C. M.; Sharma, A. Z.; Hallas, A. M.; Wilson, M. N.; Munsie, T. J. S.; Flacau, R.; Wiebe, C. R.; Gaulin, B. D.; Luke, G. M.; Greedan, J. E.

2016-10-01

Three closely related double perovskites (DP) based on the 5 d2 ion, O s6 +,B a2M Os O6 , with M =Mg , Zn, and Cd have been prepared and characterized using x-ray (XRD) and neutron diffraction (ND), dc magnetization, heat capacity, and muon spin relaxation (μ SR ) techniques. All three are cubic, Fm-3 m , at ambient temperature from XRD with Δ d /d ˜5 ×10-4 resolution. For both M =Mg and Zn, ND data at 3.5 K and lower, Δ d /d =2 ×10-3 , resolution show no signs of a distortion. The results are compared with the known DP material, B a2CaOs O6 , which shows antiferromagnetic (AF) order below TN=49 K and a moderate frustration index, f ˜4 , (f =| θCW|/ TN ), where θCW is the Curie-Weiss temperature. B a2MgOs O6 with a unit cell constant a0=8.0757 (1 ) Å , 3% smaller than for B a2CaOs O6 , also shows Néel order below TN=51 K with f ˜2 . However, B a2ZnOs O6,a0=8.0975 (1 ) Å , 0.27% larger than B a2MgOs O6 , does not show Néel order from either heat capacity or μ SR data. A zero field cooled/field cooled (ZFC/FC) irreversibility occurs near 30 K and a broad heat capacity anomaly is detected at a similar temperature. The μ SR data are consistent with a weak spin ordering with an onset below 28 K but with a coexisting dynamic component. B a2CdOs O6 with a0=8.3190 (1 ) Å , 0.5% smaller than B a2CaOs O6 , shows no evidence for any type of order/spin freezing to 0.47 K from any of the measurement techniques applied. The results for M =Zn and Cd appear to lie outside of the mean field theory of Chen and Balents [Phys. Rev. B 84, 094420 (2011), 10.1103/PhysRevB.84.094420] for cubic d2 DP with strong spin orbit coupling, but B a2MgOs O6 , along with B a2CaOs O6 , is likely one of the three predicted AF phases. The remarkable contrast between the doppelgänger pairs M =Mg /Zn and M =Ca /Cd may be traceable to differences in electronic structure of the diamagnetic M ions. All of the super-super exchange pathways in these DP materials involve Os-O-M -O-Os linkages.

High burden of Aspergillus fumigatus infection among chronic respiratory diseases.

PubMed

Fukuda, Yosuke; Homma, Tetsuya; Suzuki, Shintaro; Takuma, Takahiro; Tanaka, Akihiko; Yokoe, Takuya; Ohnishi, Tsukasa; Niki, Yoshihito; Sagara, Hironori

2018-01-01

Aspergillus fumigatus (AF) is a ubiquitous fungus in our environment and causes severe airway disorders. Chronic respiratory diseases (CRDs) are a series of chronic airway and lung diseases. Although both are chronic disorders, however, the relationships between AF and CRDs are still unclear. Therefore, we examined 104 Aspergillus species (spp.) isolated samples in our hospital during three consecutive years to further elucidate the relationships between Aspergillus spp. and CRDs. Based on sample isolates, we then grouped these into two groups, AF and non-AF, to retrospectively analyse the clinical features and to clarify the relationships between AF and CRDs. Importantly, the manifestation of CRD was more frequent in the AF group than in the non-AF group ( p = 0.035). Among CRDs, lung fibrosis was more evident in the AF group ( p = 0.025). Moreover, diabetes mellitus was tended to be evident in AF group than non-AF group ( p = 0.035). In conclusion, CRDs, especially lung fibrosis, were highly prevalent in AF group than non-AF group.

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

PubMed

Swerdlow, C D; Schsls, W; Dijkman, B; Jung, W; Sheth, N V; Olson, W H; Gunderson, B D

2000-02-29

To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

Aspergillus fumigatus (Af) Hydroxamate Siderophores Protect Formation of Af Biofilms from the Pseudomonas aeruginosa (Pa) Product Pyoverdine

PubMed Central

Sass, Gabriele; Stevens, David A

2017-01-01

Abstract Background Pa and Af are pathogens frequently found together in airways of immunocompromised patients and patients with cystic fibrosis (CF). Hence, interactions of Pa and Af require understanding. Both Pa and Af are crucially dependent on the availability of iron, and therefore are competitors in their microenvironment. We have shown, using deletion mutants of Pa, that the Pa siderophore pyoverdine, the dominant Pa inhibitor of Af, interferes with Af biofilms by iron chelation, and denial of iron to the fungus. Methods Protective compounds in Af supernatants were evaluated using assays for the quantification of Af biofilm metabolism by XTT measurement, spectrometric pyoverdine measurement, as well as Chrome Azorole S (CAS) assay for the determination of siderophore production. Results Here we provide evidence that whereas iron usage by Af promotes pyoverdine production by Pa, Af has developed a defense mechanism against anti-fungal pyoverdine effects. The ability of Af to produce hydroxamate siderophores, and shed these into the surrounding medium, where they sequester and transport iron, is a key factor for Af self-defense against Pa. Under low iron conditions, such as in the presence of high amounts of the Pa siderophore pyoverdine, siderophore-bound iron is then fed to Af, protecting the fungus from iron starvation. Af with a deletion mutation in sidA, a gene essential for the production of hydroxamate siderophores, was significantly more sensitive to Pa supernatants, as well as pure pyoverdine, than wild-type Af. Af supernatants, produced in the presence of celastrol, an inhibitor of SidA-generated biosynthesis of siderophores, or produced by the sidA mutant, were not able to protect Af from iron starvation. Conclusion Interference with the iron-dependent Af self-defense mechanism might represent a new approach for therapy against aspergillosis. Disclosures All authors: No reported disclosures.

Magnitude of increase in QTc interval after initiation of dofetilide in patients with persistent atrial fibrillation is associated with increased rates of pharmacological cardioversion and long-term freedom from recurrent atrial fibrillation.

PubMed

Huang, Henry D; Waks, Jonathan W; Steinhaus, Daniel A; Zimetbaum, Peter

2016-07-01

Dofetilide is a class III antiarrhythmic drug approved for the treatment of atrial fibrillation (AF). Dofetilide-induced corrected QT (QTc) interval prolongation is a surrogate for the degree of drug effect, but the relationships between drug-induced QTc interval prolongation, pharmacological cardioversion (PCV), and freedom from recurrent AF are unclear. The purpose of this study was to assess associations between QTc interval change during dofetilide initiation and PCV and long-term AF recurrence. We performed retrospective analyses of a prospective cohort of patients with AF admitted for dofetilide initiation between 2001 and 2014. Clinical characteristics and electrocardiographic variables were assessed. We evaluated outcomes of successful PCV in patients with persistent AF and time to recurrence of AF in patients with paroxysmal and persistent AF. During the study, 243 patients with persistent AF and 176 patients with paroxysmal AF initiated dofetilide. PCV occurred in 93/243 (41.7%) patients with persistent AF. After multivariable adjustment, QTc interval change was associated with PCV (adjusted odds ratio 1.21; P = .003 per 10-ms QTc increase). Inhospital QTc interval change was associated with long-term freedom from AF in patients with persistent AF (adjusted hazard ratio 0.92; P = .011 at 4 years per 10-ms QTc increase), but not in patients with paroxysmal AF. In patients with persistent AF, PCV was also associated with long-term freedom from recurrent AF (adjusted hazard ratio 0.62; P = .009 at 4 years). The magnitude of QTc interval prolongation during dofetilide initiation is an independent predictor of successful PCV and long-term freedom from arrhythmia in patients with persistent AF. QTc interval change had no association with AF recurrence in patients with paroxysmal AF, suggesting that different mechanisms of arrhythmogenesis may be operant in different AF types. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Complex Transcriptional Control of the Antibiotic Regulator afsS in Streptomyces: PhoP and AfsR Are Overlapping, Competitive Activators▿

PubMed Central

Santos-Beneit, Fernando; Rodríguez-García, Antonio; Martín, Juan F.

2011-01-01

The afsS gene of several Streptomyces species encodes a small sigma factor-like protein that acts as an activator of several pathway-specific regulatory genes (e.g., actII-ORF4 and redD in Streptomyces coelicolor). The two pleiotropic regulators AfsR and PhoP bind to overlapping sequences in the −35 region of the afsS promoter and control its expression. Using mutated afsS promoters containing specific point mutations in the AfsR and PhoP binding sequences, we proved that the overlapping recognition sequences for AfsR and PhoP are displaced by 1 nucleotide. Different nucleotide positions are important for binding of AfsR or PhoP, as shown by electrophoretic mobility shift assays and by reporter studies using the luxAB gene coupled to the different promoters. Mutant promoter M5 (with a nucleotide change at position 5 of the consensus box) binds AfsR but not PhoP with high affinity (named “superAfsR”). Expression of the afsS gene from this promoter led to overproduction of actinorhodin. Mutant promoter M16 binds PhoP with extremely high affinity (“superPhoP”). Studies with ΔafsR and ΔphoP mutants (lacking AfsR and PhoP, respectively) showed that both global regulators are competitive transcriptional activators of afsS. AfsR has greater influence on expression of afsS than PhoP, as shown by reverse transcriptase PCR (RT-PCR) and promoter reporter (luciferase) studies. These two high-level regulators appear to integrate different nutritional signals (particularly phosphate limitation sensed by PhoR), S-adenosylmethionine, and other still unknown environmental signals (leading to AfsR phosphorylation) for the AfsS-mediated control of biosynthesis of secondary metabolites. PMID:21378195

Ethnic distribution of ECG predictors of atrial fibrillation and its impact on understanding the ethnic distribution of ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Soliman, Elsayed Z; Prineas, Ronald J; Case, L Douglas; Zhang, Zhu-ming; Goff, David C

2009-04-01

The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, chi(2), and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P<0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors (P<0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks.

Association of a Family History of Atrial Fibrillation With Incidence and Outcomes of Atrial Fibrillation: A Population-Based Family Cohort Study.

PubMed

Chang, Shang-Hung; Kuo, Chang-Fu; Chou, I-Jun; See, Lai-Chu; Yu, Kuang-Hui; Luo, Shue-Fen; Huang, Lu-Hsiang; Zhang, Weiya; Doherty, Michael; Wen, Ming-Shien; Kuo, Chi-Tai; Yeh, Yung-Hsin

2017-08-01

The heritability of atrial fibrillation (AF), the contribution of genetic and environmental factors, and the association of a family history of AF with prognosis are unclear. To measure genetic and environmental factors in the familial aggregation of AF and to estimate the association of a family history of AF with major adverse cardiovascular events (MACE). In this Taiwanese nationwide population-based study among more than 23 million people, a custom data set was obtained using the data of all patients having a diagnosis of AF recorded between January 1996 and December 2013 in the Taiwan National Health Insurance Research Database. The study population comprised all 23 422 955 individuals registered with the database in 2013, of whom 177 770 had a diagnosis of AF and were included in the heritability estimation. From the latter, a subgroup of patients having newly diagnosed AF with a first-degree relative affected by AF between 2000 and 2010 were selected and matched 1:4 to controls without a family history for estimating MACE-free survival. The dates of analysis were January 2010 to December 2013. The prevalence and relative risk of AF in relatives of patients with AF, as well as the relative contributions of heritability and shared and nonshared environmental factors to AF susceptibility. Also measured was MACE-free survival after AF was diagnosed. In total, 1510 patients (204 [13.5%] female; mean [SD] age, 57.9 [9.2] years) had newly diagnosed AF with a first-degree relative affected by AF. Individuals with a first-degree relative affected by AF had a relative risk of 1.92 (95% CI, 1.84-1.99) for AF. The accountability for the phenotypic variance of AF was 19.9% for genetic factors (heritability), 3.5% for shared environmental factors, and 76.6% for nonshared environmental factors. After matching for age, sex, hypertension, type 2 diabetes, previous stroke, and anticoagulation, incident AF patients with vs without an affected first-degree relative had similar MACE-free survival. Genetic and environmental factors were associated with AF, with nonshared environmental factors accounting for three-fourths of the phenotypic variance in Taiwan. Patients having AF with a first-degree relative affected by AF did not have more MACE. Therefore, family history may not be particularly informative in the diagnosis or management of AF.

Common Atrial Fibrillation Risk Alleles at 4q25 Predict Recurrence after Catheter-based Atrial Fibrillation Ablation

PubMed Central

Shoemaker, M. Benjamin; Muhammad, Raafia; Parvez, Babar; White, Brenda W.; Streur, Megan; Song, Yanna; Stubblefield, Tanya; Kucera, Gayle; Blair, Marcia; Rytlewski, Jason; Parvathaneni, Sunthosh; Nagarakanti, Rangadham; Saavedra, Pablo; Ellis, Christopher; Whalen, S. Patrick; Roden, Dan M; Darbar, Dawood

2012-01-01

Background Common single nucleotide polymorphisms (SNPs) at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical AF. Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5–30% of AF cases. Objective To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. Methods Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years, 71% male, 89% typical AF) between 2004 and 2011. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF; [AT/AF]). Results Two-hundred AT/AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76 95% confidence interval [CI] 0.6–0.95, P=0.016) compared with wild-type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio = 0.79, 95% CI 0.62–0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio = 0.61, 95% CI 0.37–1.0) (P=0.037). Conclusion Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of predominately typical AF patients. Our findings suggest the rs2200733 polymorphism may hold promise as an as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation. PMID:23178686

A Specific Antibody to Neuropeptide AF1 (KNEFIRFamide) Recognizes a Small Subset of Neurons in Ascaris suum: Differences from Caenorhabditis elegans

PubMed Central

Sithigorngul, Paisarn; Jarecki, Jessica L.; Stretton, Antony O.W.

2016-01-01

A monoclonal antibody, AF1-003, highly specific to the Ascaris suum neuropeptide AF1 (KNEFIRFamide), was generated. This antibody binds strongly to AF1 and extremely weakly to other peptides with C-terminal FIR-Famide: AF5 (SGKPTFIRFamide), AF6 (FIRFamide), and AF7 (AGPRFIRFamide). It does not recognize 35 other AF (A. suum FMRFamide-like) peptides at the highest concentration tested, nor does it recognize FMRFamide. When crude peptide extracts of A. suum are fractionated by two-step HPLC, the only fractions recognized by AF1-003 are those comigrating with synthetic AF1. By immunocytochemistry, antibody AF1-003 recognizes a small subset of the 298 neurons of A. suum: these include the paired URX and RIP neurons, two pairs of lateral ganglion neurons in the head, and the unpaired PQR and PDA or -B tail neurons that send processes to the head along the dorsal and ventral nerve cords, respectively. AF1 immunoreactivity is also seen in three pairs of pharyngeal neurons. Mass spectroscopy (MS) shows the presence of AF1 in the head, pharynx, and dorsal and ventral nerve cords. In A. suum, the neurons that contain AF1 show little overlap with neurons that express green fluorescent protein constructs targeting the flp-8 gene, which encodes AF1 in Caenorhabditis elegans (Kim and Li [2004] J. Comp. Neurol. 475:540– 550); the URX neurons express AF1 in both species, but, in C. elegans, flp-8 expression was not detected in RIP, PQR, and PDA or -B or in the pharynx. Other, less specific monoclonal antibodies recognize AF1, as well as other peptides to differing degrees; these antibodies are useful reagents for determination of neuronal morphology. PMID:21452223

Atrial Fibrillation Detection During 24-Hour Ambulatory Blood Pressure Monitoring: Comparison With 24-Hour Electrocardiography.

PubMed

Kollias, Anastasios; Destounis, Antonios; Kalogeropoulos, Petros; Kyriakoulis, Konstantinos G; Ntineri, Angeliki; Stergiou, George S

2018-07-01

This study assessed the diagnostic accuracy of a novel 24-hour ambulatory blood pressure (ABP) monitor (Microlife WatchBP O3 Afib) with implemented algorithm for automated atrial fibrillation (AF) detection during each ABP measurement. One hundred subjects (mean age 70.6±8.2 [SD] years; men 53%; hypertensives 85%; 17 with permanent AF; 4 paroxysmal AF; and 79 non-AF) had simultaneous 24-hour ABP monitoring and 24-hour Holter monitoring. Among a total of 6410 valid ABP readings, 1091 (17%) were taken in ECG AF rhythm. In reading-to-reading ABP analysis, the sensitivity, specificity, and accuracy of ABP monitoring in detecting AF were 93%, 87%, and 88%, respectively. In non-AF subjects, 12.8% of the 24-hour ABP readings indicated false-positive AF, of whom 27% were taken during supraventricular premature beats. There was a strong association between the proportion of false-positive AF readings and that of supraventricular premature beats ( r =0.67; P <0.001). Receiver operating characteristic curve revealed that in paroxysmal AF and non-AF subjects, AF-positive readings at 26% during 24-hour ABP monitoring had 100%/85% sensitivity/specificity (area under the curve 0.91; P <0.01) for detecting paroxysmal AF. These findings suggest that in elderly hypertensives, a novel 24-hour ABP monitor with AF detector has high sensitivity and moderate specificity for AF screening during routine ABP monitoring. Thus, in elderly hypertensives, a 24-hour ABP recording with at least 26% of the readings suggesting AF indicates a high probability for AF diagnosis and should be regarded as an indication for performing 24-hour Holter monitoring. © 2018 American Heart Association, Inc.

Accumulation, sources and health risks of trace metals in elevated geochemical background soils used for greenhouse vegetable production in southwestern China.

PubMed

Zhang, Haidong; Huang, Biao; Dong, Linlin; Hu, Wenyou; Akhtar, Mohammad Saleem; Qu, Mingkai

2017-03-01

Greenhouse vegetable cultivation with substantive manure and fertilizer input on soils with an elevated geochemical background can accumulate trace metals in soils and plants leading to human health risks. Studies on trace metal accumulation over a land use shift duration in an elevated geochemical background scenario are lacking. Accumulation characteristics of seven trace metals in greenhouse soil and edible plants were evaluated along with an assessment of the health risk to the consumers. A total of 118 greenhouse surface soils (0-20cm) and 30 vegetables were collected from Kunming City, Yunnan Province, southwestern China, and analyzed for total Cd, Pb, Cu, Zn, As, Hg, and Cr content by ICP-MS and AFS. The trace metals were ordered Cu>Cd>Hg>Zn>Pb>As>Cr in greenhouse soils accumulation level, and the geo-accumulation index suggested the soil more severely polluted with Cd, Cu, Hg and Zn. The greenhouse and open-field soils had significant difference in Cd, Cr and Zn. The duration of shift from paddy to greenhouse land-use significantly influenced trace metal accumulation with a dramatic change during five to ten year greenhouse land-use, and continuous increase of Cd and Hg. A spatial pattern from north to south for Cd and Hg and a zonal pattern for Cu and Zn were found. An anthropogenic source primarily caused trace metal accumulation, where the principal component analysis/multiple linear regression indicated a contribution 61.2%. While the assessment showed no potential risk for children and adults, the hazard health risks index was greater than one for adolescents. The extended duration of land use as greenhouses caused the trace metal accumulation, rotation in land use should be promoted to reduce the health risks. Copyright © 2016. Published by Elsevier Inc.

Incident Atrial Fibrillation and the Risk of Congestive Heart Failure, Myocardial Infarction, End-Stage Kidney Disease, and Mortality Among Patients With a Decreased Estimated GFR.

PubMed

Massicotte-Azarniouch, David; Kuwornu, John Paul; Carrero, Juan-Jesus; Lam, Ngan N; Molnar, Amber O; Zimmerman, Deborah; McCallum, Megan K; Garg, Amit X; Sood, Manish M

2018-02-01

The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. Population-based retrospective cohort study from Ontario, Canada. 1,422,978 adult residents with eGFRs < 90mL/min/1.73m 2 from April 1, 2006, through March 31, 2015. A diagnosis of AF at hospitalization. Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m 2 . Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Structure and Function of the Sterol Carrier Protein-2 N-Terminal Presequence†

PubMed Central

Martin, Gregory G.; Hostetler, Heather A.; McIntosh, Avery L.; Tichy, Shane E.; Williams, Brad J.; Russell, David H.; Berg, Jeremy M.; Spencer, Thomas A.; Ball, Judith; Kier, Ann B.; Schroeder, Friedhelm

2008-01-01

Although sterol carrier protein-2 (SCP-2) is encoded as a precursor protein (proSCP-2), little is known regarding the structure and function of the 20-amino acid N-terminal presequence. As shown herein, the presequence contains significant secondary structure and alters SCP-2: (i) secondary structure (CD), (ii) tertiary structure (aqueous exposure of Trp shown by UV absorbance, fluorescence, fluorescence quenching), (iii) ligand binding site [Trp response to ligands, peptide cross-linked by photoactivatable free cholesterol (FCBP)], (iv) selectivity for interaction with anionic phospholipid-rich membranes, (v) interaction with a peroxisomal import protein [FRET studies of Pex5p(C) binding], the N-terminal presequence increased SCP-2’s affinity for Pex5p(C) by 10-fold, and (vi) intracellular targeting in living and fixed cells (confocal microscopy). Nearly 5-fold more SCP-2 than proSCP-2 colocalized with plasma membrane lipid rafts/caveolae (AF488-CTB), 2.8-fold more SCP-2 than proSCP-2 colocalized with a mitochondrial marker (Mitotracker), but nearly 2-fold less SCP-2 than proSCP-2 colocalized with peroxisomes (AF488-antibody to PMP70). These data indicate the importance of the N-terminal presequence in regulating SCP-2 structure, cholesterol localization within the ligand binding site, membrane association, and, potentially, intracellular targeting. PMID:18465878

[Influence of sinus rhythm restoration and maintenance on left ventricle diameter and function in patients with persistent atrial fibrillation--one year follow-up].

PubMed

Kosior, Dariusz A; Szulc, Marcin; Stawicki, Sławomir; Roik, Marek; Rabczenko, Daniel; Opolski, Grzegorz

2005-01-01

Aim of our study was to determine the dynamics of selected echocardiographic parameters after sinus rhythm (SR) restoration and maintenance in pts with persistent nonvalvular atrial fibrillation (AF) during one year follow-up period. Our study population comprised 104 pts (F/M 33/71; mean age 60.4 +/- 7.4) assigned to SR restoration and maintenance with serial antiarrhythmic drug usage, for whom transthoracic echocardiographic (TTE) variables were recorded prior to, 2 and 12 months after cardioversion (CD). Left ventricle diastolic diameter and fractional shortening were variables of interest. SR was presented in 66 (63.5%) pts at one year. There was no significant differences in left ventricle diastolic diameter during the follow up. A significant increase in left ventricular fractional shortening (29.9 +/- 6.9% vs 34.5 +/- 8.9%; p < 0.001) was found in pts assigned to the sinus rhythm restoration according to intention-to-treat analysis. Such trend was noted only in pts who maintained SR during the follow up (29.9 +/- 7.6% vs 35.6 +/- 9.3%; p < 0.001). Among all considered variables only value of left ventricular fractional shortening increased after successful CV of persistent AF in one year follow-up.

An accurate homogenized tissue phantom for broad spectrum autofluorescence studies: a tool for optimizing quantum dot-based contrast agents

NASA Astrophysics Data System (ADS)

Roy, Mathieu; Wilson, Brian C.

2008-02-01

We are investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). The present studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. These contrast optimization studies require optical phantoms that simulate tissue autofluorescence, absorption and scattering over the entire visible spectrum, while allowing us to control the optical thickness. We present an optical phantom made of fresh homogenized tissue diluted in water. The homogenized tissue is poured into a clear polymer tank designed to hold a QD-loaded silica capillary in its center. Because of the non-linear effects of absorption and scattering on measured autofluorescence, direct comparison between results obtained using tissue phantoms of different concentration is not possible. We introduce mathematical models that make it possible to perform measurements on diluted tissue homogenates and subsequently extrapolate the results to intact (non-diluted) tissue. Finally, we present preliminary QD contrast data showing that the 380-420 nm spectral window is optimal for surface QD imaging.

Health Information in Somali (Af-Soomaali )

MedlinePlus

... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Pendulum Exercises for Shoulder - Af-Soomaali (Somali) Bilingual PDF ... Af-Soomaali (Somali) Bilingual PDF Health Information Translations Pendulum Exercises for Shoulder - Af-Soomaali (Somali) Bilingual PDF ...

Neuropsychological profiles of three sisters homozygous for the fragile X premutation

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

Mazzocco, M.M.M.; Holden, J.J.A.

1996-08-09

Fragile X syndrome (fraX) is associated with an amplification of a CGG repeat within the fraX mental retardation (FMR-1) gene. We describe an exceptional family in which 3 adult sisters are homozygous for the FMR-1 premutation. Each sister inherited 2 premutation alleles (ca. 80 CGG repeats) from their biologically unrelated parents. The 3 sisters were administered measures of executive function, visual spatial, memory, and verbal skills. Deficiencies in the first 2 of these domains have been reported among females with the full mutation. The sisters` performances were compared with available normative data and with published group means for females affectedmore » by fraX. These women did not appear to have verbal or memory difficulties. None of the women demonstrated a global executive function deficit, and none had global deficits in spatial ability. The profiles of these sisters are consistent with reports that the fragile X premutation does not affect cognitive performance. 31 refs., 1 fig., 4 tabs.« less

Detection, breakpoint identification and detailed characterisation of a CNV at the FRA16D site using SNP assays.

PubMed

Winchester, L; Newbury, D F; Monaco, A P; Ragoussis, J

2008-01-01

Copy Number Variants (CNV) and other submicroscopic structural changes are now recognised to be widespread across the human genome. We show that SNP data generated for association study can be utilised for the identification of deletion CNVs. During analysis of data for an SNP association study for Specific Language Impairment (SLI) a deletion was identified. SLI adversely affects the language development of children in the absence of any obvious cause. Previous studies have found linkage to a region on chromosome 16. The deletion was located in a known fragile site FRA16D in intron 5-6 of the WWOX gene (also known as FOR). Changes in the FRA16D site have been previously linked to cancer and are often characterised in cell lines. A long-range PCR assay was used to confirm the existence of the deletion. We also show the breakpoint identification and large-scale characterisation of this CNV in a normal human sample set. Copyright 2009 S. Karger AG, Basel.

Relationship of Preexisting Cardiovascular Comorbidities to Newly Diagnosed Atrial Fibrillation After Ischemic Stroke.

PubMed

Bisson, Arnaud; Clementy, Nicolas; Bodin, Alexandre; Angoulvant, Denis; Babuty, Dominique; Lip, Gregory Y H; Fauchier, Laurent

2017-10-01

There remains uncertainty as whether newly diagnosed atrial fibrillation (AF) after ischemic stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms. We aimed to determine whether cardiovascular comorbidities in patients with new AF after ischemic stroke differ from patients with previous known AF or without AF. This French longitudinal cohort study was based on the database covering hospital care from 2009 to 2012 for the entire population. Of 336 291 patients with ischemic stroke, 240 459 (71.5%) had no AF and 95 832 (28.5%) had previously known AF at baseline. Patients without previous AF had a mean CHA 2 DS 2 -VASc score of 4.98±1.63 SD. During a mean follow-up of 7.9±11.5 months, 14 095 (5.9%) of these patients had incident AF, representing an annual incidence of AF after ischemic stroke of 8.9 per 100 person-years (95% confidence interval, 8.8-9.0). New AF patients had higher CHA 2 DS 2 -VASc score, more likely comorbidities, and more frequent history of previous transient ischemic attack than patients with previous known AF or without AF. Preexisting cardiovascular comorbidities underlie AF newly diagnosed after stroke. Consequently, these high-risk patients should be closely monitored for incident AF to facilitate an earlier diagnosis of AF and avoid stroke with appropriate thromboprophylaxis. © 2017 American Heart Association, Inc.

Early, de novo atrial fibrillation after coronary artery bypass grafting: Facts and features.

PubMed

Yaksh, Ameeta; Kik, Charles; Knops, Paul; van Ettinger, Maarten J B; Bogers, Ad J J C; de Groot, Natasja M S

2017-02-01

Knowledge of the mechanism underlying post-operative atrial fibrillation (PoAF) is essential for development of preventive measures. The incidence and characteristics of both PoAF and supraventricular premature beats triggering PoAF, their interrelationship and alterations over time have never been examined. The goal of this study is therefore to examine the correlation between the incidence and characteristics of supraventricular premature beats (SVPBs) and PoAF episodes in patients undergoing CABG in the first five post-operative days. PoAF episodes (N=327) and SVPBs (N=141,873) were characterized in 29 patients (63±9 years; 22 (76%) male) undergoing coronary artery bypass grafting and compared with a control group of patients without PoAF by using continuous cardiac rhythm monitoring during the first 5 days after surgery. Most patients (N=18, 62%) had multiple PoAF episodes; the median number of PoAF episodes per patient was 3 and varied between 1 and 139. The majority of PoAF episodes developed on the second and third post-operative day (55%). The averaged median duration of PoAF episodes per patient was 469±1085 min. Patients with PoAF had a higher SVPBs burden compared to subjects without PoAF (0.9% vs 0.2%, P<.001). SVPBs initiating PoAF had shorter coupling intervals than SVPBs which did not initiate PoAF episodes (58% vs 64% (P<.001) and were preceded by heart rate acceleration. PoAF episodes are mainly repetitive though transient in nature. There was a considerable inter-individual variation in both AF and SVPB characteristics, despite a similar underlying clinical profile. The SVPB burden is higher in patients with PoAF and the mode of onset is characterized by short coupled SVPBs. Determination of individual post-operative dysrhythmia profiles enables identification of patients at risk for developing PoAF. Copyright © 2016 Elsevier Inc. All rights reserved.

Is HATCH score a reliable predictor of atrial fibrillation after cavotricuspid isthmus ablation for typical atrial flutter?

PubMed

García-Seara, Javier; Gude Sampedro, Francisco; Martínez Sande, Jose L; Fernández López, Xesus Alberte; Rodríguez Mañero, Moisés; González Melchor, Laila; Alvarez Alvarez, Belén; Iglesias Alvarez, Diego; González Juanatey, José Ramón

2016-09-01

We determined the effectiveness of the HATCH score in patients with typical atrial flutter (AFl) undergoing cavotricuspid isthmus (CTI) ablation to predict long-term atrial fibrillation (AF). We conducted an observational retrospective single-center cohort study including all patients admitted to our hospital for a CTI ablation between 1998 and 2010. The patients were divided into four categories: 1) new-onset AF (no prior AF and AF during follow-up (FU)); 2) old AF (prior AF and no AF during FU); 3) prior and post AF (AF prior and post CTI ablation); and 4) no AF. Four hundred and eight patients were included. In patients without prior AF, the hazard ratio (HR) for new-onset AF during FU was 0.98 (CI 95%: 0.65-1.50; p = 0.95) and 1.00 (CI 95%: 0.57-1.77; p = 0.98) for HATCH ≥ 2 and HATCH ≥ 3, respectively. In patients with prior AF, the HR for AF was 1.41 (CI 95%: 0.87-2.28; p = 0.17) and 1.79 (CI 95%: 0.96-3.35; p = 0.06), for HATCH ≥ 2 and HATCH ≥ 3, respectively. Left atrial enlargement was positively correlated with the occurrence of AF during FU, especially in the subgroup without prior AF, which had a HR of 2.44 (CI 95%: 1.35-4.40; p = 0.003), a HR of 2.88 (CI 95%: 1.36-6.10; p = 0.006) and a HR of 3.68 (CI 95%: 1.71-7.94; p = 0.001), for slight, moderate and severely dilated left atrial dimension, respectively, compared with a normal value. HATCH score did not predict AF in patients with typical AFl who underwent CTI ablation. Basal left atrium dimension could help predict new-onset AF.

Identification of U2AF(35)-dependent exons by RNA-Seq reveals a link between 3′ splice-site organization and activity of U2AF-related proteins

PubMed Central

Kralovicova, Jana; Knut, Marcin; Cross, Nicholas C. P.; Vorechovsky, Igor

2015-01-01

The auxiliary factor of U2 small nuclear RNA (U2AF) is a heterodimer consisting of 65- and 35-kD proteins that bind the polypyrimidine tract (PPT) and AG dinucleotides at the 3′ splice site (3′ss). The gene encoding U2AF35 (U2AF1) is alternatively spliced, giving rise to two isoforms U2AF35a and U2AF35b. Here, we knocked down U2AF35 and each isoform and characterized transcriptomes of HEK293 cells with varying U2AF35/U2AF65 and U2AF35a/b ratios. Depletion of both isoforms preferentially modified alternative RNA processing events without widespread failure to recognize 3′ss or constitutive exons. Over a third of differentially used exons were terminal, resulting largely from the use of known alternative polyadenylation (APA) sites. Intronic APA sites activated in depleted cultures were mostly proximal whereas tandem 3′UTR APA was biased toward distal sites. Exons upregulated in depleted cells were preceded by longer AG exclusion zones and PPTs than downregulated or control exons and were largely activated by PUF60 and repressed by CAPERα. The U2AF(35) repression and activation was associated with a significant interchange in the average probabilities to form single-stranded RNA in the optimal PPT and branch site locations and sequences further upstream. Although most differentially used exons were responsive to both U2AF subunits and their inclusion correlated with U2AF levels, a small number of transcripts exhibited distinct responses to U2AF35a and U2AF35b, supporting the existence of isoform-specific interactions. These results provide new insights into function of U2AF and U2AF35 in alternative RNA processing. PMID:25779042

The Role of U2AF1 Mutations in the Pathogenesis of Myelodysplastic Syndromes

DTIC Science & Technology

2015-10-01

mutation, U2AF1(S34F), on hematopoiesis and pre-mRNA splicing in vivo, we created doxycycline-inducible U2AF1(WT) and U2AF1(S34F) transgenic mice...U2AF1(S34F) versus U2AF1(WT). Together, these results suggest that mutant U2AF1 expression contributes to the altered hematopoiesis and pre-mRNA...Spliceosome, Mouse Model, Hematopoiesis , RNA-seq, U2AF1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME

Installation Restoration Program. Phase 1 - Records Search AAC-Northern Region, Galena AFS, Campion AFS, Cape Lisburne AFS, Fort Yukon AFS, Indian Mountain AFS, Kotzebue AFS, Murphy Dome AFS, and Tin City AFS

DTIC Science & Technology

1985-09-01

GM SILTY GRAVEL GP POORLY GRADED GRAVEL SM SILTY SAND SP POORLY GRADED SAND SW WELL GRADED SAND ML LOW PLASTICITY SILT SOURCE: INSTALLATION DOCUMENTS... plastic on the side toward th’e beach in an attempt to prevent migration of fuel. to the beach. During the site visit for this Phase I IRP study the...Force have included garbage, refuse, incinerator ash (since 1975), wood, metal, plastic and bulky - materials such as construction and demolition debris

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis.

PubMed

Kanthan, Senthooran Kathirgama; Bush, Andrew; Kemp, Michael; Buchdahl, Roger

2007-09-01

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function. (c) 2007 Wiley-Liss, Inc.

Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.

PubMed

Oba, Kageyuki; Maeda, Minetaka; Maimaituxun, Gulinu; Yamaguchi, Satoshi; Arasaki, Osamu; Fukuda, Daiju; Yagi, Shusuke; Hirata, Yukina; Nishio, Susumu; Iwase, Takashi; Takao, Shoichiro; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Harada, Masafumi; Masuzaki, Hiroaki; Sata, Masataka; Shimabukuro, Michio

2018-05-25

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m 2 ) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m 2 , P<0.01). The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Maximizing Performance: Augmented Feedback, Focus of Attention, and/or Reward?

PubMed

Wälchli, Michael; Ruffieux, Jan; Bourquin, Yann; Keller, Martin; Taube, Wolfgang

2016-04-01

Different approaches like providing augmented feedback (aF), applying an external focus of attention (EF), or rewarding participants with money (RE) have been shown to instantly enhance motor performance. So far, these approaches have been tested either in separate studies or directly against each other. However, there is no study that combined aF, EF, and/or RE to test whether this provokes additional benefits. The aim of the present study was therefore to identify the most powerful combination. Eighteen participants performed maximal countermovement jumps in six different conditions: neutral (NE), aF, RE, aF + EF, aF + RE, and aF + EF + RE. Participants demonstrated the highest jump heights with aF + EF, followed by aF + EF + RE, aF + RE, aF, RE, and finally, NE. Activity of the M. rectus femoris differed significantly between conditions resulting in lower muscular activity in aF + EF and aF + EF + RE compared with NE. All other parameters, such as ground reaction forces and joint angles, were comparable across conditions. This is the first study showing superior performance when combining aF with EF. As reduced muscular activity was found only in conditions with EF, it is argued in line with the constrained action hypothesis that adopting an EF improves movement efficiency. In contrast, aF seems to rather enhance (intrinsic) motivation. However, monetary reward did not further amplify performance.

Flare Ribbons Approach Observed by the Interface Region Imaging Spectrograph and the Solar Dynamics Observatory

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

Li, Ting; Zhang, Jun; Hou, Yijun, E-mail: liting@nao.cas.cn

We report flare ribbons approach (FRA) during a multiple-ribbon M-class flare on 2015 November 4 in NOAA AR 12443, obtained by the Interface Region Imaging Spectrograph and the Solar Dynamics Observatory. The flare consisted of a pair of main ribbons and two pairs of secondary ribbons. The two pairs of secondary ribbons were formed later than the appearance of the main ribbons, with respective time delays of 15 and 19 minutes. The negative-polarity main ribbon spread outward faster than the first secondary ribbon with the same polarity in front of it, and thus the FRA was generated. Just before theirmore » encounter, the main ribbon was darkening drastically and its intensity decreased by about 70% in 2 minutes, implying the suppression of main-phase reconnection that produced two main ribbons. The FRA caused the deflection of the main ribbon to the direction of secondary ribbon with a deflection angle of about 60°. A post-approach arcade was formed about 2 minutes later and the downflows were detected along the new arcade with velocities of 35–40 km s{sup −1}, indicative of the magnetic restructuring during the process of FRA. We suggest that there are three topological domains with footpoints outlined by the three pairs of ribbons. Close proximity of these domains leads to deflection of the ribbons, which is in agreement with the magnetic field topology.« less

Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation.

PubMed

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2010-10-01

Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right-dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K(+) currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of I(K1) (Kir2.1 and Kir2.3) and I(K,ACh) (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) I(K,ACh) was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced I(K,ACh) in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches.

Ethnic Distribution of ECG Predictors of Atrial Fibrillation and Its Impact on Understanding the Ethnic Distribution of Ischemic Stroke in the Atherosclerosis Risk in Communities (ARIC) Study

PubMed Central

Soliman, Elsayed Z.; Prineas, Ronald J.; Case, L. Douglas; Zhang, Zhu-ming; Goff, David C.

2009-01-01

Background and Purpose The paradox of the reported low prevalence of atrial fibrillation (AF) in blacks compared with whites despite higher stroke rates in the former could be related to limitations in the current methods used to diagnose AF in population-based studies. Hence, this study aimed to use the ethnic distribution of ECG predictors of AF as measures of AF propensity in different ethnic groups. Methods The distribution of baseline measures of P-wave terminal force, P-wave duration, P-wave area, and PR duration (referred to as AF predictors) were compared by ethnicity in 15 429 participants (27% black) from the Atherosclerosis Risk in Communities (ARIC) study by unpaired t test, χ2, and logistic-regression analysis, as appropriate. Cox proportional-hazards analysis was used to separately examine the association of AF predictors with incident AF and ischemic stroke. Results Whereas AF was significantly less common in blacks compared with whites (0.24% vs 0.95%, P<0.0001), similar to what has been reported in previous studies, blacks had significantly higher and more abnormal values of AF predictors (P<0.0001 for all comparisons). Black ethnicity was significantly associated with abnormal AF predictors compared with whites; odds ratios for different AF predictors ranged from 2.1 to 3.1. AF predictors were significantly and independently associated with AF and ischemic stroke with no significant interaction between ethnicity and AF predictors, findings that further justify using AF predictors as an earlier indicator of future risk of AF and stroke. Conclusions There is a disconnect between the ethnic distribution of AF predictors and the ethnic distribution of AF, probably because the former, unlike the latter, do not suffer from low sensitivity. These results raise the possibility that blacks might actually have a higher prevalence of AF that might have been missed by previous studies owing to limited methodology, a difference that could partially explain the greater stroke risk in blacks. PMID:19213946

Left-to-Right Atrial Inward Rectifier Potassium Current Gradients in Patients With Paroxysmal Versus Chronic Atrial Fibrillation

PubMed Central

Voigt, Niels; Trausch, Anne; Knaut, Michael; Matschke, Klaus; Varró, András; Van Wagoner, David R.; Nattel, Stanley; Ravens, Ursula; Dobrev, Dobromir

2018-01-01

Background Recent evidence suggests that atrial fibrillation (AF) is maintained by high-frequency reentrant sources with a left-to-right–dominant frequency gradient, particularly in patients with paroxysmal AF (pAF). Unequal left-to-right distribution of inward rectifier K+ currents has been suggested to underlie this dominant frequency gradient, but this hypothesis has never been tested in humans. Methods and Results Currents were measured with whole-cell voltage-clamp in cardiomyocytes from right atrial (RA) and left (LA) atrial appendages of patients in sinus rhythm (SR) and patients with AF undergoing cardiac surgery. Western blot was used to quantify protein expression of IK1 (Kir2.1 and Kir2.3) and IK,ACh (Kir3.1 and Kir3.4) subunits. Basal current was ≈2-fold larger in chronic AF (cAF) versus SR patients, without RA-LA differences. In pAF, basal current was ≈2-fold larger in LA versus RA, indicating a left-to-right atrial gradient. In both atria, Kir2.1 expression was ≈2-fold greater in cAF but comparable in pAF versus SR. Kir2.3 levels were unchanged in cAF and RA-pAF but showed a 51% decrease in LA-pAF. In SR, carbachol-activated (2 μmol/L) IK,ACh was 70% larger in RA versus LA. This right-to-left atrial gradient was decreased in pAF and cAF caused by reduced IK,ACh in RA only. Similarly, in SR, Kir3.1 and Kir3.4 proteins were greater in RA versus LA and decreased in RA of pAF and cAF. Kir3.1 and Kir3.4 expression was unchanged in LA of pAF and cAF. Conclusions Our results support the hypothesis that a left-to-right gradient in inward rectifier background current contributes to high-frequency sources in LA that maintain pAF. These findings have potentially important implications for development of atrial-selective therapeutic approaches. PMID:20657029

Silent Atrial Fibrillation in Elderly Pacemaker Users: A Randomized Trial Using Home Monitoring.

PubMed

Lima, Ceb; Martinelli, M; Peixoto, G L; Siqueira, S F; Wajngarten, Maurício; Silva, Rodrigo Tavares; Costa, Roberto; Filho, Roberto; Ramires, José Antônio Franchini

2016-05-01

Pacemaker with remote monitoring (PRM) may be useful for silent atrial fibrillation (AF) detection. The aims of this study were to evaluate the incidence of silent AF, the role of PRM, and to determine predictors of silent AF occurrence. Three hundred elderly patients with permanent pacemaker (PPM) were randomly assigned to the remote group (RG) or control group (CG). All patients received PPM with remote monitoring capabilities. Primary end point was AF occurrence rate and the secondary end points were time to AF detection and number of days with AF. During the average follow-up of 15.7±7.7 months, AF episodes were detected in 21.6% (RG = 24% vs CG = 19.3%, P = 0.36]. There was no difference in the time to detect the first AF episode. However, the median time to detect AF recurrence in the RG was lower than that in the CG (54 days vs 100 days, P = 0.004). The average number of days with AF was 16.0 and 51.2 in the RG and CG, respectively (P = 0.028). Predictors of silent AF were left atrial diameter (odds ratio [OR] 1.2; 95% CI = 1.1-1.3; P < 0.001) and diastolic dysfunction (OR 4.8; 95% CI = 1.6-14.0; P = 0.005). The incidence of silent AF is high in elderly patients with pacemaker; left atrial diameter and diastolic dysfunction were predictors of its occurrence. AF monitoring by means of pacemaker is a valuable tool for silent AF detection and continuous remote monitoring allows early AF recurrence detection and reduces the number of days with AF. © 2015 Wiley Periodicals, Inc.

Association of Left Atrial Function Index With Late Atrial Fibrillation Recurrence after Catheter Ablation.

PubMed

Sardana, Mayank; Ogunsua, Adedotun A; Spring, Matthew; Shaikh, Amir; Asamoah, Owusu; Stokken, Glenn; Browning, Clifford; Ennis, Cynthia; Donahue, J Kevin; Rosenthal, Lawrence S; Floyd, Kevin C; Aurigemma, Gerard P; Parikh, Nisha I; McManus, David D

2016-12-01

Although catheter ablation (CA) for atrial fibrillation (AF) is commonly used to improve symptoms, AF recurrence is common and new tools are needed to better inform patient selection for CA. Left atrial function index (LAFI), an echocardiographic measure of atrial mechanical function, has shown promise as a noninvasive predictor of AF. We hypothesized that LAFI would relate to AF recurrence after CA. All AF patients undergoing index CA were enrolled in a prospective institutional AF Treatment Registry between 2011 and 2014. LAFI was measured post hoc from pre-ablation clinical echocardiographic images in 168 participants. Participants were mostly male (33% female), middle-aged (60 ± 10 years), obese and had paroxysmal AF (64%). Mean LAFI was 25.9 ± 17.6. Over 12 months of follow-up, 78 participants (46%) experienced a late AF recurrence. In logistic regression analyses adjusting for factors known to be associated with AF, lower LAFI remained associated with AF recurrence after CA [OR 0.04 (0.01-0.67), P = 0.02]. LAFI discriminated AF recurrence after CA slightly better than CHADS2 (C-statistic 0.60 LAFI, 0.57 CHADS2). For participants with persistent AF, LAFI performed significantly better than CHADS2 score (C statistic = 0.79 LAFI, 0.56 CHADS2, P = 0.02). LAFI, an echocardiographic measure of atrial function, is associated with AF recurrence after CA and has improved ability to discriminate AF recurrence as compared to the CHADS-2 score, especially among persistent AF patients. Since LAFI can be calculated using standard 2D echocardiographic images, it may be a helpful tool for predicting AF recurrence. © 2016 Wiley Periodicals, Inc.

DISCORDANCE BETWEEN BLUE-LIGHT AUTOFLUORESCENCE AND NEAR-INFRARED AUTOFLUORESCENCE IN AGE-RELATED MACULAR DEGENERATION.

PubMed

Heiferman, Michael J; Fawzi, Amani A

2016-12-01

To identify the origin and significance of discordance between blue-light autofluorescence (BL-AF; 488 nm) and near-infrared autofluorescence (NI-AF; 787 nm) in patients with age-related macular degeneration (AMD). A total of 86 eyes of 59 patients with a diagnosis of AMD were included in this cross-sectional study conducted between March 9, 2015 and May 1, 2015. A masked observer examined the BL-AF, NI-AF, and spectral-domain optical coherence tomography images. Areas with discordance of autofluorescence patterns between NI-AF and BL-AF images were correlated with structural findings at the corresponding location in optical coherence tomography scans. Seventy-nine eyes had discordance between BL-AF and NI-AF. The most common optical coherence tomography finding accounting for these discrepancies was pigment migration accounting for 35 lesions in 21 eyes. The most clinically relevant finding was geographic atrophy missed on BL-AF in 7 eyes. Our findings indicate that variations in the distribution of lipofuscin, melanin and melanolipofuscin account for the majority of discordance between BL-AF and NI-AF. Given our finding of missed geographic atrophy lesions on BL-AF in 24% of eyes with geographic atrophy (7/29 eyes), clinicians should consider multimodal imaging, including NI-AF and optical coherence tomography, especially in clinical trials of geographic atrophy.

Discordance between Blue-Light Autofluorescence and Near-Infrared Autofluorescence in Age-Related Macular Degeneration

PubMed Central

Heiferman, Michael J.; Fawzi, Amani A.

2016-01-01

Purpose To identify the origin and significance of discordance between blue-light autofluorescence (BL-AF; 488nm) and near-infrared autofluorescence (NI-AF; 787nm) in patients with age-related macular degeneration (AMD). Methods A total of 86 eyes of 59 patients with a diagnosis of AMD were included in this cross-sectional study conducted between March 9, 2015 and May 1, 2015. A masked observer examined the BL-AF, NI-AF, and spectral-domain optical coherence tomography (OCT) images. Areas with discordance of autofluorescence patterns between NI-AF and BL-AF images were correlated with structural findings at the corresponding location in OCT scans. Results 79 eyes had discordance between BL-AF and NI-AF. The most common OCT finding accounting for these discrepancies was pigment migration accounting for 35 lesions in 21 eyes. The most clinically relevant finding was geographic atrophy missed on BL-AF in seven eyes. Conclusions Our findings indicate that variations in the distribution of lipofuscin, melanin and melanolipofuscin account for the majority of discordance between BL-AF and NI-AF. Given our finding of missed geographic atrophy lesions on BL-AF in 24% of eyes with geographic atrophy (7/29 eyes), clinicians should consider multimodal imaging, including NI-AF and OCT, especially in clinical trials of geographic atrophy. PMID:28005672

Intercellular diffusion of a fluorescent sucrose analog via the septal junctions in a filamentous cyanobacterium.

PubMed

Nürnberg, Dennis J; Mariscal, Vicente; Bornikoel, Jan; Nieves-Morión, Mercedes; Krauß, Norbert; Herrero, Antonia; Maldener, Iris; Flores, Enrique; Mullineaux, Conrad W

2015-03-17

Many filamentous cyanobacteria produce specialized nitrogen-fixing cells called heterocysts, which are located at semiregular intervals along the filament with about 10 to 20 photosynthetic vegetative cells in between. Nitrogen fixation in these complex multicellular bacteria depends on metabolite exchange between the two cell types, with the heterocysts supplying combined-nitrogen compounds but dependent on the vegetative cells for photosynthetically produced carbon compounds. Here, we used a fluorescent tracer to probe intercellular metabolite exchange in the filamentous heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. We show that esculin, a fluorescent sucrose analog, is incorporated by a sucrose import system into the cytoplasm of Anabaena cells. The cytoplasmic esculin is rapidly and reversibly exchanged across vegetative-vegetative and vegetative-heterocyst cell junctions. Our measurements reveal the kinetics of esculin exchange and also show that intercellular metabolic communication is lost in a significant fraction of older heterocysts. SepJ, FraC, and FraD are proteins located at the intercellular septa and are suggested to form structures analogous to gap junctions. We show that a ΔsepJ ΔfraC ΔfraD triple mutant shows an altered septum structure with thinner septa but a denser peptidoglycan layer. Intercellular diffusion of esculin and fluorescein derivatives is impaired in this mutant, which also shows a greatly reduced frequency of nanopores in the intercellular septal cross walls. These findings suggest that FraC, FraD, and SepJ are important for the formation of junctional structures that constitute the major pathway for feeding heterocysts with sucrose. Anabaena and its relatives are filamentous cyanobacteria that exhibit a sophisticated form of prokaryotic multicellularity, with the formation of differentiated cell types, including normal photosynthetic cells and specialized nitrogen-fixing cells called heterocysts. The question of how heterocysts communicate and exchange metabolites with other cells in the filament is key to understanding this form of bacterial multicellularity. Here we provide the first information on the intercellular exchange of a physiologically important molecule, sucrose. We show that a fluorescent sucrose analog can be imported into the Anabaena cytoplasm by a sucrose import system. Once in the cytoplasm, it is rapidly and reversibly exchanged among all of the cells in the filament by diffusion across the septal junctions. Photosynthetically produced sucrose likely follows the same route from cytoplasm to cytoplasm. We identify some of the septal proteins involved in sucrose exchange, and our results indicate that these proteins form structures functionally analogous to metazoan gap junctions. Copyright © 2015 Nürnberg et al.

A QoS scheme for a congestion core network based on dissimilar QoS structures in smart-phone environments.

PubMed

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones.

A QoS Scheme for a Congestion Core Network Based on Dissimilar QoS Structures in Smart-Phone Environments

PubMed Central

Hong, Sung-Ryong; Na, Wonshik; Kang, Jang-Mook

2010-01-01

This study suggests an approach to effective transmission of multimedia content in a rapidly changing Internet environment including smart-phones. Guaranteeing QoS in networks is currently an important research topic. When transmitting Assured Forwarding (AF) packets in a Multi-DiffServ network environment, network A may assign priority in an order AF1, AF2, AF3 and AF4; on the other hand, network B may reverse the order to a priority AF4, AF3, AF2 and AF1. In this case, the AF1 packets that received the best quality of service in network A will receive the lowest in network B, which may result in dropping of packets in network B and vice versa. This study suggests a way to guarantee QoS between hosts by minimizing the loss of AF packet class when one network transmits AF class packets to another network with differing principles. It is expected that QoS guarantees and their experimental value may be utilized as principles which can be applied to various mobile-web environments based on smart-phones. PMID:22163453

Performance and age of African and non-African runners in half- and full marathons held in Switzerland, 2000–2010

PubMed Central

Aschmann, André; Knechtle, Beat; Cribari, Marco; Rüst, Christoph Alexander; Onywera, Vincent; Rosemann, Thomas; Lepers, Romuald

2013-01-01

Background Endurance running performance of African (AF) and non-African (NAF) athletes is investigated, with better performances seen for Africans. To date, no study has compared the age of peak performance between AF and NAF runners. The present research is an analysis of the age and running performance of top AF and NAF athletes, using the hypothesis that AF athletes were younger and faster than NAF athletes. Methods Age and performance of male and female AF and NAF athletes in half-marathons and marathons held in Switzerland in 2000–2010 were investigated using single and multilevel hierarchical regression analyses. Results For half-marathons, male NAF runners were older than male AF runners (P = 0.02; NAF, 31.1 years ± 6.4 years versus AF, 26.2 years ± 4.9 years), and their running time was longer (P = 0.02; NAF, 65.3 minutes ± 1.7 minutes versus AF, 64.1 minutes ± 0.9 minutes). In marathons, differences between NAF and AF male runners in age (NAF, 33.0 years ± 4.8 years versus AF, 28.6 years ± 3.8 years; P < 0.01) and running time (NAF, 139.5 minutes ± 5.6 minutes versus AF, 133.3 minutes ± 2.7 minutes; P < 0.01) were more pronounced. There was no difference in age (NAF, 31.0 years ± 7.0 years versus AF, 26.7 years ± 6.0 years; P > 0.05) or running time (NAF, 75.0 minutes ± 3.7 minutes versus AF, 75.6 minutes ± 5.3 minutes; P > 0.05) between NAF and AF female half-marathoners. For marathoners, NAF women were older than AF female runners (P = 0.03; NAF, 31.6 years ± 4.8 years versus AF, 27.8 years ± 5.3 years), but their running times were similar (NAF, 162.4 minutes ± 7.2 minutes versus AF, 163.0 minutes ± 7.0 minutes; P > 0.05). Conclusion In Switzerland, the best AF male half-marathoners and marathoners were younger and faster than the NAF counterpart runners. In contrast to the results seen in men, AF and NAF female runners had similar performances. Future studies need to investigate performance and age of AF and NAF marathoners in the World Marathon Majors Series. PMID:24379724

Estrogen Receptor α L543A,L544A Mutation Changes Antagonists to Agonists, Correlating with the Ligand Binding Domain Dimerization Associated with DNA Binding Activity*

PubMed Central

Arao, Yukitomo; Hamilton, Katherine J.; Coons, Laurel A.; Korach, Kenneth S.

2013-01-01

A ligand-dependent nuclear transcription factor, ERα has two transactivating functional domains (AF), AF-1 and AF-2. AF-1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding domain (LBD) of the ERα protein. Helix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible to an active or inactive form. We demonstrated previously that the ERα mutant (AF2ER) possessing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestrant/ICI182780 (ICI) or 4-hydoxytamoxifen (OHT) into agonists in the AF2ER knock-in mouse. Our previous in vitro studies suggested that the mode of AF2ER activation is similar to the partial agonist activity of OHT for WT-ERα. However, it is still unclear how antagonists activate ERα. To understand the molecular mechanism of antagonist reversal activity, we analyzed the correlation between the ICI-dependent estrogen-responsive element-mediated transcription activity of AF2ER and AF2ER-LBD dimerization activity. We report here that ICI-dependent AF2ER activation correlated with the activity of AF2ER-LBD homodimerization. Prevention of dimerization impaired the ICI-dependent ERE binding and transcription activity of AF2ER. The dislocation of H12 caused ICI-dependent LBD homodimerization involving the F-domain, the adjoining region of H12. Furthermore, F-domain truncation also strongly depressed the dimerization of WT-ERα-LBD with antagonists but not with E2. AF2ER activation levels with ICI, OHT, and raloxifene were parallel with the degree of AF2ER-LBD homodimerization, supporting a mechanism that antagonist-dependent LBD homodimerization involving the F-domain results in antagonist reversal activity of H12-mutated ERα. PMID:23733188

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Impact of acute atrial fibrillation termination and prolongation of atrial fibrillation cycle length on the outcome of ablation of persistent atrial fibrillation: A substudy of the STAR AF II trial.

PubMed

Kochhäuser, Simon; Jiang, Chen-Yang; Betts, Timothy R; Chen, Jian; Deisenhofer, Isabel; Mantovan, Roberto; Macle, Laurent; Morillo, Carlos A; Haverkamp, Wilhelm; Weerasooriya, Rukshen; Albenque, Jean-Paul; Nardi, Stefano; Menardi, Endrj; Novak, Paul; Sanders, Prashanthan; Verma, Atul

2017-04-01

Controversy exists about the impact of acute atrial fibrillation (AF) termination and prolongation of atrial fibrillation cycle length (AFCL) during ablation on long-term procedural outcome. The purpose of this study was to analyze the influence of AF termination and AFCL prolongation on freedom from AF in patients from the STAR AF II (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial-Part II) trial. Acute changes in AFCL and AF termination were collected during the index procedure of the STAR AF II trial and compared to recurrence of AF at 18 months. Recurrence was assessed by ECG, Holter (3, 6, 9, 12, 18 months), and weekly transtelephonic ECG monitoring for 18 months. AF terminated in 8% of the pulmonary vein isolation (PVI) arm, 45% in the PVI+complex electrogram arm, and 22% of the PVI+linear ablation arm (P <.001), but freedom from AF did not differ among the 3 groups (P = .15). Freedom from AF was significantly higher in patients who presented to the laboratory in sinus rhythm (SR) compared to those without AF termination (63% vs 44%, P = .007). Patients with AF termination had an intermediate outcome (53%) that was not significantly different from those in SR (P = .84) or those who did not terminate (P = .08). AF termination was a univariable predictor of success (P = .007), but by multivariable analysis, presence of early SR was the strongest predictor of success (hazard ratio 0.67, P = .004). Prolongation of AFCL was not predictive of 18-month freedom from AF. Acute AF termination and prolongation in AFCL did not consistently predict 18-month freedom from AF. Presence of SR before or early during the ablation was the strongest predictor of better outcome. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study.

PubMed

Lubitz, Steven A; Yin, Xiaoyan; McManus, David D; Weng, Lu-Chen; Aparicio, Hugo J; Walkey, Allan J; Rafael Romero, Jose; Kase, Carlos S; Ellinor, Patrick T; Wolf, Philip A; Seshadri, Sudha; Benjamin, Emelia J

2017-02-01

To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF. © 2017 American Heart Association, Inc.

Termination of persistent atrial fibrillation during pulmonary vein isolation: insight from the MAGIC-AF trial.

PubMed

Singh, Sheldon M; d'Avila, Andre; Kim, Young-Hoon; Aryana, Arash; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Barrett, Conor D; Heist, E Kevin; Parides, Michael K; Thorpe, Kevin E; Reddy, Vivek Y

2017-10-01

Controversy on the optimal ablation strategy for persistent atrial fibrillation (AF) exists with limited work evaluating a strategy of pulmonary vein isolation (PVI) alone when AF terminates during PVI. Thirty-five patients had AF termination during PVI in the Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF; ClinicalTrials.gov number: NCT01014741) study. The objective of the current study is to report the 1-year outcome after PVI alone in this unique patient group. The 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs was reported for the 35 patients in the MAGIC-AF study with persistent AF termination during or upon completion of PVI. Freedom from recurrent atrial arrhythmia was achieved in 60% of patients where AF terminated during PVI. Cavotricuspid isthmus flutter was common when AF terminated to a macro re-entrant flutter during PVI, and responsible for 92% of all flutter circuits with AF termination. Persistent AF termination during PVI may identify a subgroup of patients who experience a similar long-term clinical outcome with PVI ablation alone when compared with other more extensive persistent AF ablation strategies. Pulmonary vein isolation alone may be an appropriate tactic in this subgroup of persistent AF patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Major element chemistry of glasses in Apollo 14 soil 14156.

NASA Technical Reports Server (NTRS)

Reid, A. M.; Ridley, W. I.; Harmon, R. S.; Jakes, P.

1973-01-01

Glasses in a soil sample (14156) from the middle layer of the trench at the Fra Mauro landing site show a wide range of compositions clustered around certain preferred compositions. Ninety per cent of the glasses are of two major types - Fra Mauro basalt (63%) with high K and 17 wt % Al2O3 and Highland basalt or anorthositic gabbro (27%) with low K and 25 to 26 wt % Al2O3. The glass population is almost identical with that of the comprehensive soil 14259.

Simulation of a Rotorcraft in Turbulent Flows

DTIC Science & Technology

1991-09-01

Knot) Aircraft Parallel Aircraft Parallel Aircraft Parallel To Ship’s To Port-To-Star- To Starboard- Centerline board Landing To-Port Landing Lineup ...Line Lineup Line 345 to 015/35 340 to 005/45 345 to 005145 016 t,) 040/30 006 to 035!35 006 to 025/40 041 to 180/45 036 to 050/30 026 to 040/30 181 to...WIND /FRA3 LOW REYNOLD’S NUMBER AERODYNAMICS FOR NACA0012 AIRFOIL REQUIRES DS/DM NACA0012/AIRFOIL NO SEQUENTIAL FILES REQUIRED INPUT FOR FORCE FRA3

Protective effects of Urtica dioica seed extract in aflatoxicosis: histopathological and biochemical findings.

PubMed

Uyar, A; Yener, Z; Dogan, A

2016-04-01

The ameliorative potential and antioxidant capacity of an extract of Urtica dioica seeds (UDS) was investigated using histopathological changes in liver and kidney, measuring serum marker enzymes, antioxidant defence systems and lipid peroxidation (malondialdehyde (MDA)) content in various tissues of broilers exposed to aflatoxin (AF). A total of 32 broilers were divided randomly into 4 groups: control, UDS extract-treated, AF-treated and AF+UDS extract-treated. Broilers in control and UDS extract-treated groups were fed on a diet without AF. The AF-treated group and AF+UDS extract-treated groups were treated with an estimated 1 mg total AF/kg feed. The AF+UDS extract groups received in addition 30 ml UDS extract/kg diet for 21 d. The AF-treated group had significantly decreased body weight gain when compared to the other groups. Biochemical analysis showed a small increase in the concentrations of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and lactate dehydrogenase in the AF-treated group compared to that of the control group, whereas concentrations of these enzymes were decreased in the AF+UDS group compared to that of the AF-treated group. Administration of supplementary UDS extract helped restore the AF-induced increase in MDA and reduced the antioxidant system towards normality, particularly in the liver, brain, kidney and heart. Hepatorenal protection by UDS extracts was further supported by the almost normal histology in AF+UDS extract-treated group as compared to the degenerative changes in the AF-treated broilers. It was concluded that UDS extract has a protective hepatorenal effect in broilers affected by aflatoxicosis, probably acting by promoting the antioxidative defence systems.

Anticoagulation therapy and clinical outcomes in patients with recently diagnosed atrial fibrillation: Insights from the ARISTOTLE trial.

PubMed

Guimarães, Patrícia O; Wojdyla, Daniel M; Alexander, John H; Thomas, Laine; Alings, Marco; Flaker, Greg C; Al-Khatib, Sana M; Hanna, Michael; Horowitz, John D; Wallentin, Lars; Granger, Christopher B; Lopes, Renato D

2017-01-15

Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed AF had a similar risk of stroke/systemic embolism (HR=1.07, 95% CI=0.80-1.42; p=0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR=1.21, 95% CI=1.02-1.43; p=0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AF diagnosis (all interaction p-values >0.12). Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators.

PubMed

Hart, R G; Pearce, L A; Rothbart, R M; McAnulty, J H; Asinger, R W; Halperin, J L

2000-01-01

This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation (AF). Although intermittent AF is common, relatively little is known about the attendant risk of stroke. A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years. Independent risk factors for ischemic stroke were identified by multivariate analysis. Patients with intermittent AF were, on average, younger (66 vs. 70 years, p < 0.001), were more often women (37% vs. 26% p < 0.001) and less often had heart failure (11% vs. 21%, p < 0.001) than those with sustained AF. The annualized rate of ischemic stroke was similar for those with intermittent (3.2%) and sustained AF (3.3%). In patients with intermittent AF, independent predictors of ischemic stroke were advancing age (relative risk [RR] = 2.1 per decade, p < 0.001), hypertension (RR = 3.4, p = 0.003) and prior stroke (RR = 4.1, p = 0.01). Of those with intermittent AF predicted to be high risk (24%), the observed stroke rate was 7.8% per year (95% confidence interval 4.5 to 14). In this large cohort of AF patients given aspirin, those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors. Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation. High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF.

Clinical predictors of risk for atrial fibrillation: implications for diagnosis and monitoring.

PubMed

Brunner, Kyle J; Bunch, T Jared; Mullin, Christopher M; May, Heidi T; Bair, Tami L; Elliot, David W; Anderson, Jeffrey L; Mahapatra, Srijoy

2014-11-01

To create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF). The AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA2DS2-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis. A total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820). We developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Calreticulin overexpression correlates with integrin-α5 and transforming growth factor-β1 expression in the atria of patients with rheumatic valvular disease and atrial fibrillation.

PubMed

Zhao, Fei; Zhang, Shijiang; Shao, Yongfeng; Wu, Yanhu; Qin, Jianwei; Chen, Yijiang; Chen, Liang; Gu, Haitao; Wang, Xiaowei; Huang, Chenjun; Zhang, Wei

2013-10-03

The aim of this study was to determine whether altered calreticulin expression and distribution contribute to the pathogenesis of atrial fibrillation (AF) associated with valvular heart disease (VHD). AF affects electrophysiological and structural changes that exacerbate AF. Atrial remodeling reportedly underlies AF generation, but the precise mechanism of atrial remodeling in AF remains unclear. Right and left atrial specimens were obtained from 68 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (SR; n=25), paroxysmal AF (PaAF; n=11), and persistent AF (PeAF; AF lasting >6 months; n=32) groups. Calreticulin, integrin-α5, and transforming growth factor-β1 (TGF-β1) mRNA and protein expression were measured. We also performed immunoprecipitation for calreticulin with either calcineurin B or integrin-α5. Calreticulin, integrin-α5, and TGF-β1 mRNA and protein expression were increased in the AF groups, especially in the left atrium in patients with mitral valve disease. Calreticulin interacted with both calcineurin B and integrin-α5. Integrin-α5 expression correlated with TGF-β1 expression, while calreticulin expression correlated with integrin-α5 and TGF-β1 expression. Despite similar cardiac function classifications, calreticulin expression was greater in the PeAF group than in the SR group. Calreticulin, integrin-α5, and TGF-β1 expression was increased in atrial tissue in patients with AF and was related to AF type, suggesting that calreticulin is involved in the pathogenesis of AF in VHD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Targeting Stable Rotors to Treat Atrial Fibrillation.

PubMed

Narayan, Sanjiv M; Krummen, David E

2012-09-01

Therapy for atrial fibrillation (AF) remains suboptimal, in large part because its mechanisms are unclear. While pulmonary vein ectopy may trigger AF, it remains uncertain how AF, once triggered, is actually sustained. Recent discoveries show that human AF is maintained by a small number of rotors or focal sources. AF sources are widely distributed in patient-specific locations, often remote from pulmonary veins and in the right atrium and stable for prolonged periods of time. In a multicentre experience, brief targeted ablation at sources (focal impulse and rotor modulation [FIRM]) terminated AF predominantly to sinus rhythm prior to pulmonary vein isolation and eliminated AF on rigorous followup. This review summarises the evidence for stable rotors and focal sources of human AF and their clinical role as ablation targets to eliminate paroxysmal, persistent and long-standing persistent AF.

Obstructive Sleep Apnoea and Atrial Fibrillation

PubMed Central

Zhang, Ling; Hou, Yuemei; Po, Sunny S

2015-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with significant morbidity and mortality. Obstructive sleep apnoea (OSA) is common among patients with AF. Growing evidence suggests that OSA is associated with the initiation and maintenance of AF. This association is independent of obesity, body mass index and hypertension. OSA not only promotes initiation of AF but also has a significant negative impact on the treatment of AF. Patients with untreated OSA have a higher AF recurrence rate with drug therapy, electrical cardioversion and catheter ablation. Treatment with continuous positive airway pressure (CPAP) has been shown to improve AF control in patients with OSA. In this article, we will review and discuss the pathophysiological mechanisms of OSA that may predispose OSA patients to AF as well as the standard and emerging therapies for patients with both OSA and AF. PMID:26835094

Genetic Risk Prediction of Atrial Fibrillation

PubMed Central

Lubitz, Steven A.; Yin, Xiaoyan; Lin, Henry J.; Kolek, Matthew; Smith, J. Gustav; Trompet, Stella; Rienstra, Michiel; Rost, Natalia S.; Teixeira, Pedro L.; Almgren, Peter; Anderson, Christopher D.; Chen, Lin Y.; Engström, Gunnar; Ford, Ian; Furie, Karen L.; Guo, Xiuqing; Larson, Martin G.; Lunetta, Kathryn L.; Macfarlane, Peter W.; Psaty, Bruce M.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Stott, David J.; Taylor, Kent D.; Weng, Lu-Chen; Yao, Jie; Geelhoed, Bastiaan; Verweij, Niek; Siland, Joylene E.; Kathiresan, Sekar; Roselli, Carolina; Roden, Dan; van der Harst, Pim; Darbar, Dawood; Jukema, J. Wouter; Melander, Olle; Rosand, Jonathan; Rotter, Jerome I.; Heckbert, Susan R.; Ellinor, Patrick T.; Alonso, Alvaro; Benjamin, Emelia J.

2017-01-01

Background Atrial fibrillation (AF) is common and has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 controls. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1×10−3 to <1×10−8 in a prior independent genetic association study. Results Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13–1.46; P=1.5×10−4) to 1.67 (25 variants; 95%CI, 1.47–1.90; P=9.3×10−15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629–0.811; maximum ΔC statistic from clinical score alone, 0.009–0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke, versus those in the lowest quartile (95%CI, 1.39–4.58; P=2.7×10−3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20–4.40; P=0.01). Conclusions Comprehensive AF genetic risk scores were associated with incident AF beyond clinical AF risk factors, with magnitudes of risk comparable to other clinical risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts to determine whether AF genetic risk may improve identification of subclinical AF or distinguish stroke mechanisms are warranted. PMID:27793994

Impact of pre-existing or new-onset atrial fibrillation on 30-day clinical outcomes following transcatheter aortic valve replacement: Results from the BRAVO 3 randomized trial.

PubMed

Hengstenberg, Christian; Chandrasekhar, Jaya; Sartori, Samantha; Lefevre, Thierry; Mikhail, Ghada; Meneveau, Nicolas; Tron, Christophe; Jeger, Raban; Kupatt, Christian; Vogel, Birgit; Farhan, Serdar; Sorrentino, Sabato; Sharma, Madhav; Snyder, Clayton; Husser, Oliver; Boekstegers, Peter; Hambrecht, Rainer; Widder, Julian; Hildick-Smith, David; De Carlo, Marco; Wijngaard, Peter; Deliargyris, Efthymios; Bernstein, Debra; Baber, Usman; Mehran, Roxana; Anthopoulos, Prodromos; Dangas, George

2017-11-15

Prior studies have suggested that patients with atrial fibrillation (AF) undergoing transcatheter aortic valve replacement (TAVR) are at higher risk for adverse cardiovascular events. Whether procedural bivalirudin compared with unfractionated heparin (UFH) has a beneficial effect on early outcomes in these patients is unknown. We examined for the effect of baseline or new-onset AF within 30 days of TAVR and explored for the effect of bivalirudin versus UFH by AF status, on 30-day outcomes from the BRAVO 3 trial. The BRAVO-3 trial multicenter randomized trial included 802 patients undergoing transfemoral TAVR randomized to bivalirudin or UFH. We compared AF and no-AF groups and examined for 30-day Bleeding Academic Research Consortium type ≥3b bleeding, major vascular complications and all ischemic endpoints. Adjusted outcomes were analyzed using logistic regression methods. Of the study population, 41.4% (n = 332) patients had baseline or new-onset AF within 30 days of TAVR, whereas 58.6% (n = 470) had no AF. Patients with AF had greater prevalence of renal dysfunction, lower left ventricular ejection fraction, and higher euroSCORE I compared with their counterparts without AF. Among AF and no-AF patients, there were no significant baseline differences between bivalirudin and UFH groups. At 30 days the incidence of death (6.0 vs. 4.5%, P = 0.324) and stroke (3.9 vs. 2.6%, P = 0.274) was similar in AF vs. no-AF patients. However, new-onset AF (n = 38) was associated with significantly greater crude risk of 30-day stroke compared with no AF (HR 4.49, 95% CI 1.37-14.67). Regardless of AF status, there were no differences in 30-day death (P-int = 0.652) or stroke (P-int = 0.066) by anticoagulation type. Prior or new-onset AF is noted in more than one-third of patients undergoing transfemoral TAVR. Despite greater baseline comorbidities than non-AF patients, AF was not associated with significantly higher risk of adjusted 30-day outcomes. In the BRAVO 3 trial, early outcomes were similar regardless of anticoagulant strategy in each group. © 2017 Wiley Periodicals, Inc.

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping

PubMed Central

Zaman, Junaid A. B.; Narayan, Sanjiv M.

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes. PMID:26306123

Characteristic appearances of fundus autofluorescence in treatment-naive and active polypoidal choroidal vasculopathy: a retrospective study of 170 patients.

PubMed

Zhao, Xinyu; Xia, Song; Chen, Youxin

2018-06-01

To investigate the characteristic appearances of fundus autofluorescence (FAF) in patients with treatment-naive and active polypoidal choroidal vasculopathy (PCV). Cases with the diagnosis of treatment-naive and active PCV from November 2012 to May 2017 at Peking Union Medical College Hospital were retrospectively reviewed. All patients underwent comprehensive ophthalmologic examination. Autofluorescence (AF) findings were described at the retinal sites of the corresponding lesions identified and diagnosed using indocyanine green angiography and spectral-domain optical coherence tomography. One hundred seventy patients with 192 affected eyes were included. The logMAR BCVA of the patients were 0.53 ± 0.28. The six AF patterns of 243 polypoidal lesions were confluent hypo-AF with hyper-AF ring (49.8%), confluent hypo-AF (22.6%), hyper-AF with hypo-AF ring (3.7%), granular hypo-AF (7.0%), blocked hypo-AF due to hemorrhage (8.6%), and polyps without apparent AF changes (8.2%). For 146 branching vascular networks (BVNs), 97.3% were granular hypo-AF, and others were blocked hypo-AF due to hemorrhage. In eyes with treatment-naive and active PCV, the polypoidal lesions and BVNs induce characteristic FAF changes. FAF images provide reliable adjunct reference for the diagnosis of PCV.

Ablating Atrial Fibrillation: Customizing Lesion Sets Guided by Rotor Mapping.

PubMed

Zaman, Junaid A B; Narayan, Sanjiv M

2015-01-01

Ablation occupies an increasing role in the contemporary management of atrial fibrillation (AF), but results are suboptimal, particularly for persistent AF. While an anatomic approach to ablation is a highly efficacious and safe method to isolate pulmonary vein (PV) triggers, recurrence of AF is not always associated with PV reconnection, and there is compelling evidence that non-PV sites sustain AF after it is triggered. Recent developments in wide-area mapping and signal processing now identify rotors in the vast majority of AF patients that sustain AF and whose elimination improves long-term freedom from AF in multicenter studies. Investigators have now demonstrated rotor and focal sources for AF that show many analogous properties between approaches: they lie in spatially reproducible regions temporally over hours to days, and they are amenable to targeted ablation. This review outlines the rationale and technical developments supporting this mechanistic paradigm for human AF, and discusses how rotor mapping may be implemented for individual patient customization of lesion sets. Mechanistic studies are required to explain why rotor elimination (or other ablation approaches) producing long-term elimination of AF may not always terminate AF acutely, how AF correlates with structural changes on magnetic resonance imaging, and how these findings can be integrated clinically with current ablation strategies to improve patient outcomes.

Bone marrow mesenchymal stem cells from infants with MLL-AF4+ acute leukemia harbor and express the MLL-AF4 fusion gene

PubMed Central

Catalina, Purificación; Rodríguez, René; Melen, Gustavo J.; Bueno, Clara; Arriero, Mar; García-Sánchez, Félix; Lassaletta, Alvaro; García-Sanz, Ramón

2009-01-01

MLL-AF4 fusion is a hallmark genetic abnormality in infant B-acute lymphoblastic leukemia (B-ALL) known to arise in utero. The cellular origin of leukemic fusion genes during human development is difficult to ascertain. The bone marrow (BM) microenvironment plays an important role in the pathogenesis of several hematological malignances. BM mesenchymal stem cells (BM-MSC) from 38 children diagnosed with cytogenetically different acute leukemias were screened for leukemic fusion genes. Fusion genes were absent in BM-MSCs of childhood leukemias carrying TEL-AML1, BCR-ABL, AML1-ETO, MLL-AF9, MLL-AF10, MLL-ENL or hyperdiploidy. However, MLL-AF4 was detected and expressed in BM-MSCs from all cases of MLL-AF4+ B-ALL. Unlike leukemic blasts, MLL-AF4+ BM-MSCs did not display monoclonal Ig gene rearrangements. Endogenous or ectopic expression of MLL-AF4 exerted no effect on MSC culture homeostasis. These findings suggest that MSCs may be in part tumor-related, highlighting an unrecognized role of the BM milieu on the pathogenesis of MLL-AF4+ B-ALL. MLL-AF4 itself is not sufficient for MSC transformation and the expression of MLL-AF4 in MSCs is compatible with a mesenchymal phenotype, suggesting a differential impact in the hematopoietic system and mesenchyme. The absence of monoclonal rearrangements in MLL-AF4+ BM-MSCs precludes the possibility of cellular plasticity or de-differentiation of B-ALL blasts and suggests that MLL-AF4 might arise in a population of prehematopoietic precursors. PMID:19995953

African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative.

PubMed

Perez, Marco V; Hoffmann, Thomas J; Tang, Hua; Thornton, Timothy; Stefanick, Marcia L; Larson, Joseph C; Kooperberg, Charles; Reiner, Alex P; Caan, Bette; Iribarren, Carlos; Risch, Neil

2013-09-01

Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans. © 2013.

Depression and Physical Inactivity as Confounding the Effect of Obesity on Atrial Fibrillation.

PubMed

Garimella, Roja S; Sears, Samuel F; Gehi, Anil K

2016-06-01

Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m(2)) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidence, type of atrial fibrillation and risk factors for stroke: a population-based cohort study

PubMed Central

Johansson, Cecilia; Dahlqvist, Erik; Andersson, Jonas; Jansson, Jan-Håkan; Johansson, Lars

2017-01-01

Purpose The aims of this study were to estimate the incidence of atrial fibrillation and atrial flutter (AF), to assess the presence of provoking factors and risk factors for stroke and systemic embolism, and to determine the type of AF in patients with first-diagnosed AF. Patients and methods This cohort study was performed in northern Sweden between January 1, 2011 and December 31, 2012. Diagnosis registries were searched for the International Classification of Diseases-10 code for AF (I48) to identify cases of incident AF. All AF diagnoses were electrocardiogram-verified. Data pertaining to provoking factors, type of AF and presence of risk factors for stroke and systemic embolism according to the CHA2DS2-VASc score were obtained from medical records. Results The incidence of AF in the entire population was 4.0 per 1,000 person-years. The incidence was 27.5 per 1,000 person-years in patients aged ≥80 years. A total of 21% of all patients had a provoking factor in association with the first-diagnosed episode of AF. The CHA2DS2-VASc score was 2 or higher in 81% of the patients. Permanent AF was the most common type of AF (29%). Conclusion There was a considerable increase in the incidence of AF with age, and a provoking factor was found in one-fifth. The most common type of AF was permanent AF. Four in five patients had a CHA2DS2-VASc score of 2 or more. PMID:28182159

Refinement of detecting atrial fibrillation in stroke patients: results from the TRACK-AF Study.

PubMed

Reinke, F; Bettin, M; Ross, L S; Kochhäuser, S; Kleffner, I; Ritter, M; Minnerup, J; Dechering, D; Eckardt, L; Dittrich, R

2018-04-01

Detection of occult atrial fibrillation (AF) is crucial for optimal secondary prevention in stroke patients. The AF detection rate was determined by implantable cardiac monitor (ICM) and compared to the prediction rate of the probability of incident AF by software based analysis of a continuously monitored electrocardiogram at follow-up (stroke risk analysis, SRA); an optimized AF detection algorithm is proposed by combining both tools. In a monocentric prospective study 105 out of 389 patients with cryptogenic stroke despite extensive diagnostic workup were investigated with two additional cardiac monitoring tools: (a) 20 months' monitoring by ICM and (b) SRA during hospitalization at the stroke unit. The detection rate of occult AF was 18% by ICM (n = 19) (range 6-575 days) and 62% (n = 65) had an increased risk for AF predicted by SRA. When comparing the predictive accuracy of SRA to ICM, the sensitivity was 95%, specificity 35%, positive predictive value 27% and negative predictive value 96%. In 18 patients with AF detected by ICM, SRA also showed a medium risk for AF. Only one patient with a very low risk predicted by SRA developed AF revealed by ICM after 417 days. A combination of SRA and ICM is a promising strategy to detect occult AF. SRA is reliable in predicting incident AF with a high negative predictive value. Thus, SRA may serve as a cost-effective pre-selection tool identifying patients at risk for AF who may benefit from further cardiac monitoring by ICM. © 2017 EAN.

A brief history of 'lone' atrial fibrillation: from 'a peculiar pulse irregularity' to a modern public health concern.

PubMed

Potpara, Tatjana S; Lip, Gregory Y H

2015-01-01

Ever since the original description of a 'peculiar pulse irregularity', atrial fibrillation (AF) has been studied extensively and has come a long journey from the recognition of its cardiac origins, to the modern concept of AF as a serious public health challenge with profound social and economic implications. This arrhythmia affects around 2% of adult population, and the most common underlying heart diseases accompanying AF in the modern era are hypertension, heart failure and coronary artery disease, as well as valvular heart diseases and numerous other cardiac as well as non-cardiac disorders which have been shown to predispose to AF. On occasions, AF occurs in young otherwise apparently healthy individuals (so called 'lone AF'). For a long time, 'lone' AF has been believed to bear a favourable prognosis as compared to AF with underlying structural heart disease, but increasing evidence suggests that 'lone' AF patients represent a rather heterogeneous cohort, with highly variable individual risk profiles due to the presence of various subclinical cardiovascular risk factors or genetically determined subtle alterations at the cellular or molecular level. For these reasons, the existence of truly 'lone' AF has recently been questioned. In this review article, we present a brief history of the recognition of the public health burden of AF. We discuss some of the misconceptions and breakthroughs on modern knowledge on AF, including the rise (and fall) of the 'lone' AF concept.

Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering.

PubMed

Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

2007-08-01

Engineering a functional replacement for the annulus fibrosus (AF) of the intervertebral disc is contingent upon recapitulation of AF structure, composition, and mechanical properties. In this study, we propose a new paradigm for AF tissue engineering that focuses on the reconstitution of anatomic fiber architecture and uses constitutive modeling to evaluate construct function. A modified electrospinning technique was utilized to generate aligned nanofibrous polymer scaffolds for engineering the basic functional unit of the AF, a single lamella. Scaffolds were tested in uniaxial tension at multiple fiber orientations, demonstrating a nonlinear dependence of modulus on fiber angle that mimicked the nonlinearity and anisotropy of native AF. A homogenization model previously applied to native AF successfully described scaffold mechanical response, and parametric studies demonstrated that nonfibrillar matrix, along with fiber connectivity, are key contributors to tensile mechanics for engineered AF. We demonstrated that AF cells orient themselves along the aligned scaffolds and deposit matrix that contributes to construct mechanics under loading conditions relevant to the in vivo environment. The homogenization model was applied to cell-seeded constructs and provided quantitative measures for the evolution of matrix and interfibrillar interactions. Finally, the model demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered material behaved much like native tissue, suggesting that engineered constructs replicate the physiologic behavior of the single AF lamella. Constitutive modeling provides a powerful tool for analysis of engineered AF neo-tissue and native AF tissue alike, highlighting key mechanical design criteria for functional AF tissue engineering.

Opportunistic screening of atrial fibrillation by automatic blood pressure measurement in the community.

PubMed

Omboni, Stefano; Verberk, Willem J

2016-04-12

Timely detection of atrial fibrillation (AF) may effectively prevent cardiovascular consequences. However, traditional diagnostic tools are either poorly reliable (pulse palpation) or not readily accessible (ECG) in general practice. We tested whether an automatic oscillometric blood pressure (BP) monitor embedded with an algorithm for AF detection might be effective for opportunistic screening of asymptomatic AF in the community. A community-based screening campaign in an unselected population to verify the feasibility of AF screening with a Microlife WatchBP Office BP monitor with a patented AFIB algorithm. When possible AF was detected (≥2 of 3 BP measurements reporting AF), a doctor immediately performed a single-lead ECG in order to confirm or exclude the presence of the arrhythmia. The main demographic and clinical data were also collected. 220 consecutive participants from an unselected sample of individuals in a small Italian community. Number of patients detected with AF and diagnosed risk factors for AF. In 12 of 220 participants, the device detected possible AF during the BP measurement: in 4 of them (1.8%), the arrhythmia was confirmed by the ECG. Patients with AF were more likely to be older (77.0±1.2 vs 57.2±15.2 years, p=0.010), obese (50.0 vs 14.4%, p=0.048) and to suffer from a cardiovascular disease (50.0 vs 10.6%, p=0.014) than patients without AF. Participants with a positive BP AF reading and non-AF arrhythmias (n=8) did not differ in their general characteristics from participants with a negative BP AF reading and were younger than patients with AF (mean age 56.4±14.8, p=0.027; 5 of 8 participants aged <65 years). Opportunistic screening of AF by BP measurement is feasible to diagnose this arrhythmia in unaware participants, particularly in those older than 65 years, who are the target patient group recommended by current AF screening guidelines. 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/

Preventing Gut Leakiness and Endotoxemia Contributes to the Protective Effect of Zinc on Alcohol-Induced Steatohepatitis in Rats123

PubMed Central

Zhong, Wei; Li, Qiong; Sun, Qian; Zhang, Wenliang; Zhang, Jiayang; Sun, Xinguo; Yin, Xinmin; Zhang, Xiang; Zhou, Zhanxiang

2015-01-01

Background: Zinc deficiency has been well documented in alcoholic liver disease. Objective: This study was undertaken to determine whether dietary zinc supplementation provides beneficial effects in treating alcohol-induced gut leakiness and endotoxemia. Methods: Male Sprague Dawley rats were divided into 3 groups and pair-fed (PF) Lieber-DeCarli liquid diet for 8 wk: 1) control (PF); 2) alcohol-fed (AF; 5.00–5.42% wt:vol ethanol); and 3) AF with zinc supplementation (AF/Zn) at 220 ppm zinc sulfate heptahydrate. The PF and AF/Zn groups were pair-fed with the AF group. Hepatic inflammation and endotoxin signaling were determined by immunofluorescence and quantitative polymerase chain reaction (qPCR). Alterations in intestinal tight junctions and aldehyde dehydrogenases were assessed by qPCR and Western blot analysis. Results: The AF rats had greater macrophage activation and cytokine production (P < 0.05) in the liver compared with the PF rats, whereas the AF/Zn rats showed no significant differences (P > 0.05). Plasma endotoxin concentrations of the AF rats were 136% greater than those of the PF rats, whereas the AF/Zn rats did not differ from the PF rats. Ileal permeability was 255% greater in the AF rats and 19% greater in the AF/Zn rats than in the PF rats. The AF group had reduced intestinal claudin-1, occludin, and zona occludens-1 (ZO-1) expression, and the AF/Zn group had upregulated claudin-1 and ZO-1 expression (P < 0.05) compared with the PF group. The intestinal epithelial expression and activity of aldehyde dehydrogenases were elevated (P < 0.05) in the AF/Zn rats compared with those of the AF rats. Furthermore, the ileal expression and function of hepatocyte nuclear factor 4α, which was impaired in the AF group, was significantly elevated in the AF/Zn group compared with the PF group. Conclusions: The results demonstrate that attenuating hepatic endotoxin signaling by preserving the intestinal barrier contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats. PMID:26468492

Naringenin targets ERK2 and suppresses UVB-induced photoaging.

PubMed

Jung, Sung Keun; Ha, Su Jeong; Jung, Chang Hwa; Kim, Yun Tai; Lee, Hoo-Keun; Kim, Myoung Ok; Lee, Mee-Hyun; Mottamal, Madhusoodanan; Bode, Ann M; Lee, Ki Won; Dong, Zigang

2016-05-01

A number of natural phytochemicals have anti-photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase-1 (MMP-1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB-induced MMP-1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3-dimensional (3-D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm(2)) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB-induced MMP-1 expression and AP-1 activity, and strongly suppressed UVB-induced phosphorylation of Fos-related antigen (FRA)-1 at Ser265. Importantly, UVB irradiation-induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen-activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB-induced extracellular signal-regulated kinase 2 (ERK2) activity and subsequently attenuated UVB-induced phosphorylation of p90(RSK) by competitively binding with ATP. Constitutively active MEK (CA-MEK) increased FRA1 phosphorylation and expression and also induced MMP-1 expression, whereas dominant-negative ERK2 (DN-ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP-1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB-induced wrinkle formation, trans-epidermal water loss and MMP-13 expression. Naringenin exerts potent anti-photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down-regulation of AP-1 transactivation and MMP-1 expression. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Measurement of fructose-asparagine concentrations in human and animal foods.

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

Wu, Jikang; Sabag-Daigle, Anice; Metz, Thomas O.

2018-01-10

The food-borne bacterial pathogen, Salmonella enterica, can utilize fructose-asparagine (F-Asn) as the sole carbon and nitrogen source. F-Asn is the product of an Amadori rearrangement following the non-enzymatic condensation of glucose and asparagine. Heating converts F-Asn via complex Maillard reactions to a variety of molecules which contribute to the color, taste, and aroma of heated foods. Among these is acrylamide, which is present in some foods, especially in fried potato products. The F-Asn utilization pathway in Salmonella, specifically FraB, is a potential drug target because inhibition of this enzyme would lead to intoxication of Salmonella in the presence of F-Asn.more » However, F-Asn would need to be packaged with the FraB inhibitor, or available in human foods. To determine if there are foods that have sufficient F-Asn, we measured F-Asn concentrations in a variety of human and animal foods. The 399 pmol/mg F-Asn found in mouse chow is sufficient to intoxicate a Salmonella fraB mutant in mouse models of salmonellosis, and several human foods were found to have this concentration or higher (fresh apricots, lettuce, asparagus, and in canned peaches). Much higher concentrations (11,000 to 35,000 pmol/mg dry weight) were found in heat-dried apricots, apples, and asparagus. This report clarifies the origins of F-Asn as a nutrient source for Salmonella, and identifies foods that could be used in concert with a FraB inhibitor as a therapeutic agent for Salmonella.« less

Measurement of Fructose–Asparagine Concentrations in Human and Animal Foods

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

Wu, Jikang; Sabag-Daigle, Anice; Metz, Thomas O.

The food-borne bacterial pathogen, Salmonella enterica, can utilize fructose-asparagine (F-Asn) as the sole carbon and nitrogen source. F-Asn is the product of an Amadori rearrangement following the non-enzymatic condensation of glucose and asparagine. Heating converts F-Asn via complex Maillard reactions to a variety of molecules which contribute to the color, taste, and aroma of heated foods. Among these is acrylamide, which is present in some foods, especially in fried potato products. The F-Asn utilization pathway in Salmonella, specifically FraB, is a potential drug target because inhibition of this enzyme would lead to intoxication of Salmonella in the presence of F-Asn.more » However, F-Asn would need to be packaged with the FraB inhibitor, or available in human foods. To determine if there are foods that have sufficient F-Asn, we measured F-Asn concentrations in a variety of human and animal foods. The 399 pmol/mg F-Asn found in mouse chow is sufficient to intoxicate a Salmonella fraB mutant in mouse models of salmonellosis, and several human foods were found to have this concentration or higher (fresh apricots, lettuce, asparagus, and in canned peaches). Much higher concentrations (11,000 to 35,000 pmol/mg dry weight) were found in heat-dried apricots, apples, and asparagus. This report clarifies the origins of F-Asn as a nutrient source for Salmonella, and identifies foods that could be used in concert with a FraB inhibitor as a therapeutic agent for Salmonella.« less

[Prediction of round window visibility in cochlear implantation with temporal bone high resolution computed tomography].

PubMed

Sun, S P; Lu, W; Lei, Y B; Men, X M; Zuo, B; Ding, S G

2017-08-07

Objective: To discuss the prediction of round window(RW) visibility in cochlear implantation(CI) with temporal bone high resolution computed tomography(HRCT). Methods: From January 2013 to January 2017, 130 cases underwent both HRCT and CI in our hospital were analyzed. The distance from facial nerve to posterior canal wall(FWD), the angle between facial nerve and inner margin of round window(FRA), and the angle between facial nerve and tympanic anulus to inner margin of round window(FRAA) were detected at the level of round window on axial temporal bone HRCT. A line parallel to the posterior wall of ear canal was drawn from the anterior wall of facial nerve at the level of round window on axial temporal bone HRCT and its relationship with round window was detected (facial-round window line, FRL): type0-posterior to the round window, type1-between the round window, type2-anterior to the round window. Their(FWD, FRA, FRAA, FRL) relationships with intra-operative round window visibility were analyzed by SPSS 17.0 software. Results: FWD( F =18.76, P =0.00), FRA( F =34.57, P =0.00), FRAA ( F =14.24, P =0.00) could affect the intra-operative RW visibility significantly. RW could be exposed completely during CI when preoperative HRCT showing type0 FRL. RW might be partly exposed and not exposed when preoperative HRCT showing type1 and type2 FRL respectively. Conclusion: FWD, FRA, FRAA and FRL of temporal bone HRCT can predict intra-operative round window visibility effectively in CI surgery.

The efficacy of intraoperative atrial radiofrequency ablation for atrial fibrillation during concomitant cardiac surgery-the Surgical Atrial Fibrillation Suppression (SAFS) Study.

PubMed

Veasey, Rick A; Segal, Oliver R; Large, Janet K; Lewis, Michael E; Trivedi, Uday H; Cohen, Andrew S; Hyde, Jonathan A J; Sulke, A Neil

2011-10-01

Studies assessing radiofrequency ablation (RFA) for atrial fibrillation (AF) performed at the time of concomitant cardiac surgery have reported high success rates. The efficacy of this treatment has primarily been determined by a single electrocardiogram (ECG) or 24-h Holter monitor at follow-up. We sought to assess the true efficacy of this procedure using prolonged cardiac rhythm monitoring. One hundred patients with paroxysmal (n = 47) and persistent AF (n = 53) requiring cardiac surgery were enrolled. Patients were clinically reviewed 6 weeks post-operatively and were monitored with 7-day Holter with full disclosure, 6 months post-surgery. A cohort of 50 patients also underwent 7 day Holter monitoring preoperatively. AF recurrence was defined as >30 s of AF. At 6 months, 75% of patients were in sinus rhythm according to a single ECG. However, only 62% of patients were free from AF on 7-day Holter; all AF episodes in these patients were asymptomatic. The procedure resulted in a significant decrease in AF burden from 56.2% at baseline to 27.5% at 6 months follow-up, (p < 0.001). Predictors of AF recurrence were (1) pre-operative AF duration; (2) persistent compared with paroxysmal AF; (3) increasing left atrial diameter and (4) requirement for mitral valve surgery. Surgical RFA for the treatment of AF, during concomitant cardiac surgery, is a successful procedure and significantly reduces AF burden. However, 13% of patients have asymptomatic AF episodes only identified with continuous monitoring. This has important implications for post-operative anti-arrhythmic and anticoagulant management and for the definition of surgical AF ablation success.

Comparison of the origin and coupling interval between ectopy with and without atrial fibrillation initiation.

PubMed

Kanda, Takashi; Masuda, Masaharu; Fujita, Masashi; Iida, Osamu; Okamoto, Shin; Ishihara, Takayuki; Nanto, Kiyonori; Sunaga, Akihiro; Tsujimura, Takuya; Matsuda, Yasuhiro; Ohashi, Takuya; Uematsu, Masaaki

2018-01-01

Differentiation of atrial fibrillation (AF) trigger ectopy from other ectopy is often difficult. The purpose of this study was to compare the origin and coupling intervals (CI) between AF-trigger and non-AF-trigger ectopy. This study consisted of 120 patients with AF who underwent an initial ablation. Isoproterenol was infused up to 20μg/min to provoke ectopy and AF. We measured the CI of all ectopy provoked by an isoproterenol infusion. The %CI was calculated as the CI of the ectopy/P-P interval of the preceding 2 beats. A total of 117 patients had at least one ectopy, and AF was induced in 56 (47%) patients. Of the 276 ectopies observed in this study, 211 (76%) originated from pulmonary veins and 77 (28%) were AF-trigger ectopy. AF-trigger ectopy more frequently originated from pulmonary veins (PVs) (74 vs. 3, p<0.001) and had a significantly shorter CI (201±70ms vs. 365±147ms, p<0.001) and lower %CI (29±11% vs. 55±14%, p<0.001) than that of non-AF-trigger ectopy. A receiver operating characteristics analysis revealed that a %CI of 40% was the best cut-off value for differentiating whether it was an AF-trigger or not. The identified trigger group, including patients with provoked AF-trigger ectopy or ectopy with a low %CI (<40%), had a significantly better AF recurrence-free survival rate than the other group (88% vs. 65%, p=0.004). AF-trigger ectopy predominantly originated from PVs and had a short CI. These findings may be useful for estimating whether ectopies are an AF-trigger or not. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Atrial Fibrillation Genetic Risk and Ischemic Stroke Mechanisms.

PubMed

Lubitz, Steven A; Parsons, Owen E; Anderson, Christopher D; Benjamin, Emelia J; Malik, Rainer; Weng, Lu-Chen; Dichgans, Martin; Sudlow, Cathie L; Rothwell, Peter M; Rosand, Jonathan; Ellinor, Patrick T; Markus, Hugh S; Traylor, Matthew

2017-06-01

Atrial fibrillation (AF) is a leading cause of cardioembolic stroke, but the relationship between AF and noncardioembolic stroke subtypes are unclear. Because AF may be unrecognized, and because AF has a substantial genetic basis, we assessed for predisposition to AF across ischemic stroke subtypes. We examined associations between AF genetic risk and Trial of Org 10172 in Acute Stroke Treatment stroke subtypes in 2374 ambulatory individuals with ischemic stroke and 5175 without from the Wellcome Trust Case-Control Consortium 2 using logistic regression. We calculated AF genetic risk scores using single-nucleotide polymorphisms associated with AF in a previous independent analysis across a range of preselected significance thresholds. There were 460 (19.4%) individuals with cardioembolic stroke, 498 (21.0%) with large vessel, 474 (20.0%) with small vessel, and 814 (32.3%) individuals with strokes of undetermined cause. Most AF genetic risk scores were associated with stroke, with the strongest association ( P =6×10 - 4 ) attributed to scores of 944 single-nucleotide polymorphisms (each associated with AF at P <1×10 - 3 in a previous analysis). Associations between AF genetic risk and stroke were enriched in the cardioembolic stroke subset (strongest P =1.2×10 - 9 , 944 single-nucleotide polymorphism score). In contrast, AF genetic risk was not significantly associated with noncardioembolic stroke subtypes. Comprehensive AF genetic risk scores were specific for cardioembolic stroke. Incomplete workups and subtype misclassification may have limited the power to detect associations with strokes of undetermined pathogenesis. Future studies are warranted to determine whether AF genetic risk is a useful biomarker to enhance clinical discrimination of stroke pathogeneses. © 2017 American Heart Association, Inc.

Impact of Atrial Fibrillation on Healthcare Utilization in the Community: The Atherosclerosis Risk in Communities Study

PubMed Central

Bengtson, Lindsay G. S.; Lutsey, Pamela L.; Loehr, Laura R.; Kucharska‐Newton, Anna; Chen, Lin Y.; Chamberlain, Alanna M.; Wruck, Lisa M.; Duval, Sue; Stearns, Sally C.; Alonso, Alvaro

2014-01-01

Background Atrial fibrillation (AF) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF‐related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study. Methods and Results Participants with incident AF enrolled in fee‐for‐service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF, respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF, respectively. Most utilization among AF patients was attributable to non‐AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease–related reasons was 4.58 (95% CI: 3.41 to 6.16) for those with AF versus those without AF. The association between AF and healthcare utilization was similar among men and women and among white and black participants. Conclusions Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease–related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities. PMID:25359400

Increasing atrial fibrillation prevalence in acute ischemic stroke and TIA.

PubMed

Otite, Fadar Oliver; Khandelwal, Priyank; Chaturvedi, Seemant; Romano, Jose G; Sacco, Ralph L; Malik, Amer M

2016-11-08

To evaluate trends in atrial fibrillation (AF) prevalence in acute ischemic stroke (AIS) and TIA in the United States. We used the Nationwide Inpatient Sample to retrospectively compute weighted prevalence of AF in AIS (n = 4,355,140) and TIA (n = 1,816,459) patients admitted to US hospitals from 2004 to 2013. Multivariate-adjusted models were used to evaluate the association of AF with clinical factors, mortality, length of stay, and cost. From 2004 to 2013, AF prevalence increased by 22% in AIS (20%-24%) and by 38% in TIA (12%-17%). AF prevalence varied by age (AIS: 6% in 50-59 vs 37% in ≥80 years; TIA: 4% in 50-59 vs 24% in ≥80 years), sex (AIS: male 19% vs female 25%; TIA: male 15% vs female 14%), race (AIS: white 26% vs black 12%), and region (AIS: Northeast 25% vs South 20%). Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF in AIS. AF in AIS was a risk factor for in-hospital death (odds ratio 1.93, 95% confidence interval 1.89-1.98) but mortality in AIS with AF decreased from 11.6% to 8.3% (p < 0.001). Compared to no AF, AF was associated with increased cost of $2,310 and length of stay 1.1 days in AIS. AF prevalence in AIS and TIA has continued to increase. Disparity in AF prevalence in AIS and TIA exists by patient and hospital factors. AF is associated with increased mortality in AIS. Innovative AIS preventive strategies are needed in patients with AF, especially in the elderly. © 2016 American Academy of Neurology.

Evaluating the HATCH score for predicting progression to sustained atrial fibrillation in ED patients with new atrial fibrillation.

PubMed

Barrett, Tyler W; Self, Wesley H; Wasserman, Brian S; McNaughton, Candace D; Darbar, Dawood

2013-05-01

Atrial fibrillation (AF) is often first detected in the emergency department (ED). Not all AF patients progress to sustained AF (ie, episodes lasting >7 days), which is associated with increased morbidity. The HATCH score stratifies patients with paroxysmal AF according to their risk for progression to sustained AF within 1 year. The HATCH score has previously never been tested in ED patients. We evaluated the accuracy of the HATCH score to predict progression to sustained AF within 1 year of initial AF diagnosis in the ED. We conducted a retrospective cohort study of 253 ED patients with new onset AF and known rhythm status for 1 year following the initial AF detection. The exposure variable was the HATCH score at initial ED evaluation. The primary outcome was rhythm status at 1 year following initial AF diagnosis. We constructed a receiver operating characteristic curve and calculated the area under the curve to estimate the HATCH score's accuracy of predicting progression to sustained AF. Overall, 61 (24%) of 253 of patients progressed to sustained AF within 1 year of initial detection, and the HATCH score receiver operating characteristic area under the curve was 0.62 (95% confidence interval, 0.54-0.70). Among ED patients with new onset AF, the HATCH score was a modest predictor of progression to sustained AF. Because only 2 patients had a HATCH greater than 5, this previously recommended cut-point was not useful in identifying high-risk patients in this cohort. Refinement of this decision aid is needed to improve its prognostic accuracy in the ED population. Copyright © 2013 Elsevier Inc. All rights reserved.

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels

PubMed Central

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L.; Bhatnagar, Deepak; Cleveland, Thomas E.

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus. PMID:24734028

Co-inoculation of aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus to study fungal invasion, colonization, and competition in maize kernels.

PubMed

Hruska, Zuzana; Rajasekaran, Kanniah; Yao, Haibo; Kincaid, Russell; Darlington, Dawn; Brown, Robert L; Bhatnagar, Deepak; Cleveland, Thomas E

2014-01-01

A currently utilized pre-harvest biocontrol method involves field inoculations with non-aflatoxigenic Aspergillus flavus strains, a tactic shown to strategically suppress native aflatoxin-producing strains and effectively decrease aflatoxin contamination in corn. The present in situ study focuses on tracking the invasion and colonization of an aflatoxigenic A. flavus strain (AF70), labeled with green fluorescent protein (GFP), in the presence of a non-aflatoxigenic A. flavus biocontrol strain (AF36), to better understand the competitive interaction between these two strains in seed tissue of corn (Zea mays). Corn kernels that had been co-inoculated with GFP-labeled AF70 and wild-type AF36 were cross-sectioned and observed under UV and blue light to determine the outcome of competition between these strains. After imaging, all kernels were analyzed for aflatoxin levels. There appeared to be a population difference between the co-inoculated AF70-GFP+AF36 and the individual AF70-GFP tests, both visually and with pixel count analysis. The GFP allowed us to observe that AF70-GFP inside the kernels was suppressed up to 82% when co-inoculated with AF36 indicating that AF36 inhibited progression of AF70-GFP. This was in agreement with images taken of whole kernels where AF36 exhibited a more robust external growth compared to AF70-GFP. The suppressed growth of AF70-GFP was reflected in a corresponding (upto 73%) suppression in aflatoxin levels. Our results indicate that the decrease in aflatoxin production correlated with population depression of the aflatoxigenic fungus by the biocontrol strain supporting the theory of competitive exclusion through robust propagation and fast colonization by the non-aflatoxigenic fungus.

Impact of catheter ablation with remote magnetic navigation on procedural outcomes in patients with persistent and long-standing persistent atrial fibrillation.

PubMed

Jin, Qi; Pehrson, Steen; Jacobsen, Peter Karl; Chen, Xu

2015-11-01

The objectives of this study were to assess the procedural outcomes of persistent and long-standing persistent atrial fibrillation (PsAF and L-PsAF) ablation guided by remote magnetic navigation (RMN), and to detect factors predicting acute restoration of sinus rhythm (SR) by ablation with RMN. A total of 313 patients (275 male, age 59 ± 9.5 years) with PsAF (187/313) or L-PsAF (126/313) undergoing ablation using RMN were included. Patients' disease history, pulmonary venous anatomy, left atrial (LA) volume, procedure time, mapping plus ablation time, radiofrequency (RF) ablation time, fluoroscopy time, radiation dose, and complications were assessed. Stepwise regression was used to predict which variable could best predict acute restoration from AF to SR by ablation. Compared to PsAF, procedure time and RF ablation time were significantly increased in patients with L-PsAF (P = 0.01 and P < 0.001, respectively). No major complications occurred during the procedures in either PsAF or L-PsAF patients. Fifty five of 313 patients converted directly to SR by ablation. Compared to L-PsAF, the rate of SR restoration was significantly higher in PsAF (21 vs 12%, P = 0.03). Stepwise regression analysis showed LA volume was the primary parameter affecting SR restoration (P = 0.01). The LA volume of patients without direct SR restoration by ablation was 24% greater than that of patients with SR restoration (P < 0.001). Catheter ablation using RMN is a safe and effective method for PsAF and L-PsAF. LA volume could be a predictor of direct restoration of SR from sustaining AF by ablation using RMN.

Benefit of Anticoagulation Therapy in Hyperthyroidism-Related Atrial Fibrillation.

PubMed

Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah

2015-08-01

Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.

Influence of atrial fibrillation on the mortality of patients with heart failure with preserved ejection fraction.

PubMed

Franco, Jonathan; Formiga, Francesc; Cepeda, Jose; Llacer, Pau; Arévalo-Lorido, Juan; Cerqueiro, Jose; González-Franco, Alvaro; Epelde, Francesc; Manzano, Luis; Montero Pérez-Barquero, Manuel

2018-05-23

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018). In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Atrial Fibrillation in Hypertrophic Cardiomyopathy: Prevalence, Clinical Correlations, and Mortality in a Large High‐Risk Population

PubMed Central

Siontis, Konstantinos C.; Geske, Jeffrey B.; Ong, Kevin; Nishimura, Rick A.; Ommen, Steve R.; Gersh, Bernard J.

2014-01-01

Background Atrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF, identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population. Methods and Results We identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF. The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM, 650 (18%) had AF. Patients with AF were older and more symptomatic (P<0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF (P<0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM, the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death. Conclusions In this large referral HCM population, approximately 1 in 5 patients had AF. AF was a strong predictor of mortality, even after adjustment for established risk factors. PMID:24965028

Morphologies of the atria and pulmonary veins in relation to lone atrial fibrillation progression: a dual-source computed tomography scan study.

PubMed

Liu, Xing-Peng; Xu, Xia; Tian, Ying; Tang, Ri-Bo; Yu, Rong-Hui; Long, De-Yong; Sang, Cai-Hua; Jiang, Chen-Xi; Ning, Man; Dong, Jian-Zeng; Ma, Chang-Sheng

2012-11-01

Atrial Remodeling and Lone Atrial Fibrillation. We sought to investigate the role of anatomic remodeling of the atria and pulmonary veins (PVs) in the progression of lone atrial fibrillation (AF) using dual-source computed tomography (DSCT). From 1,308 consecutive patients referred for an index ablation procedure for AF, we prospectively enrolled 29 consecutive patients with recently developed (<3 months) lone persistent AF (PsAF) and 23 consecutive patients with short-lasting (6-12 months) lone PsAF, all of whom had a history of paroxysmal AF (PAF). The control group consisted of 33 patients with lone PAF. On DSCT, the recently developed PsAF group showed more extensive atrial anatomic remodeling than the PAF group as shown by ∼40% higher spot biatrial volume, even though the mean duration of continuous AF was only 6 weeks. In contrast, the DSCT variables in the recently developed PsAF group and the short-lasting PsAF group were comparable, despite the fact that the mean duration of continuous AF in the latter group was 8 months. Series of cross-sectional areas of the ostial 1.5 cm of PV trunks were comparable in the PAF and PsAF groups in all but 3 ostial planes. A higher spot left atrial volume was the only independent factor associated with the progression of lone PAF to PsAF (OR: 1.06, 95% CI: 1.03-1.09, P<0.0001) on logistic regression. Prominent anatomic remodeling of the atria, rather than the PVs, underlies the mechanism of recent progression of lone paroxysmal AF to the persistent variety. © 2012 Wiley Periodicals, Inc.

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

PubMed Central

Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Breithardt, Günter; Hankey, Graeme J.; Becker, Richard C.; Singer, Daniel E.; Halperin, Jonathan L.; Hacke, Werner; Nessel, Christopher C.; Berkowitz, Scott D.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

2015-01-01

Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF. PMID:25209598

The future of anticoagulation management in atrial fibrillation in Europe: An assessment of today's challenges with recommendations for the future.

PubMed

Lichten, Catherine A; Castle-Clarke, Sophie; Manville, Catriona; Horvath, Veronika; Robin, Enora; Krapels, Joachim; Parks, Sarah; Sim, Megan; van Zijverden, Olga; Chataway, Joanna

2015-11-30

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia, affecting approximately 1-2 per cent of the population worldwide. Those who suffer from AF have a five times higher risk of stroke. AF prevalence increases with age and it affects roughly 18 per cent of the population over 85. Consequently, as populations age, AF is becoming an increasingly significant public health issue. Over recent years there have been developments in treatment and management options, both for treating the arrhythmia directly, and assessing and reducing the risk of AF-related stroke, but there is a need to ensure that available knowledge is applied optimally to benefit patients so that opportunities to prevent AF-related stroke are not missed. The aims of this project were to assess the current landscape and explore the direction of future developments in AF management in Europe, with a focus on the use of anticoagulants in the prevention of AF-related stroke. Through rapid evidence assessment, key informant interviews, PESTLE analysis and the development and exploration of future scenarios, we have developed sets of shorter- and longer-term recommendations for improving AF-related patient outcomes. The short-term recommendations are: i) improve AF awareness among the public and policymakers; ii) support education about AF management for healthcare professionals and patients; and iii) maintain engagement in AF-related research across the health services.

An illness-specific version of the Revised Illness Perception Questionnaire in patients with atrial fibrillation (AF IPQ-R): Unpacking beliefs about treatment control, personal control and symptom triggers.

PubMed

Taylor, Elaina C; O'Neill, Mark; Hughes, Lyndsay D; Moss-Morris, Rona

2018-04-01

This study modified the Revised Illness Perception Questionnaire (IPQ-R) in patients with persistent atrial fibrillation (AF). Qualitative interviews and think-aloud techniques informed modification of the IPQ-R to be specific to AF patients. Confirmatory Factor Analysis (CFA) (n = 198) examined the validity of the modified IPQ-R (AF-IPQ-R). Exploratory factor analysis (EFA) examined the new AF-triggers scale. Construct validity examined associations between the AF-IPQ-R, quality of life (QoL) and beliefs about medicines. Test-retest and internal reliability were examined. Interviews indicated that patients viewed triggers of AF rather than initial causes of illness as more applicable. Patients believed specific behaviours such as rest could control AF. Treatment control beliefs related to pharmacological and procedural treatments. These data were used to modify the IPQ-R subscales and to develop a triggers of AF scale. CFA indicated good model fit. EFA of the triggers scale indicated three factors: emotional; health behaviours; and over-exertion triggers. Expected correlations were found between the AF-IPQ-R, QoL and treatment beliefs, evidencing good construct validity. The AF-IPQ-R showed sound psychometric properties. It provides more detailed specification than the IPQ-R of beliefs that may help to understand poor QoL in AF patients, and guidance for future interventions in this area.

Novel pharmacological targets for the rhythm control management of atrial fibrillation.

PubMed

Burashnikov, Alexander; Antzelevitch, Charles

2011-12-01

Atrial fibrillation (AF) is a growing clinical problem associated with increased morbidity and mortality. Development of safe and effective pharmacological treatments for AF is one of the greatest unmet medical needs facing our society. In spite of significant progress in non-pharmacological AF treatments (largely due to the use of catheter ablation techniques), anti-arrhythmic agents (AADs) remain first line therapy for rhythm control management of AF for most AF patients. When considering efficacy, safety and tolerability, currently available AADs for rhythm control of AF are less than optimal. Ion channel inhibition remains the principal strategy for termination of AF and prevention of its recurrence. Practical clinical experience indicates that multi-ion channel blockers are generally more optimal for rhythm control of AF compared to ion channel-selective blockers. Recent studies suggest that atrial-selective sodium channel block can lead to safe and effective suppression of AF and that concurrent inhibition of potassium ion channels may potentiate this effect. An important limitation of the ion channel block approach for AF treatment is that non-electrical factors (largely structural remodeling) may importantly determine the generation of AF, so that "upstream therapy", aimed at preventing or reversing structural remodeling, may be required for effective rhythm control management. This review focuses on novel pharmacological targets for the rhythm control management of AF. Copyright © 2011 Elsevier Inc. All rights reserved.

Modulated exchange bias in NiFe/CoO/α-Fe2O3 trilayers and NiFe/CoO bilayers

NASA Astrophysics Data System (ADS)

Li, X.; Lin, K.-W.; Yeh, W.-C.; Desautels, R. D.; van Lierop, J.; Pong, Philip W. T.

2017-02-01

While the exchange bias in ferromagnetic/antiferromagnetic (FM/AF) bilayer and FM1/AF/FM2 trilayer configurations has been widely investigated, the role of an AF2 layer in FM/AF1/AF2 trilayer configurations is still not well understood. In this work, the magnetic properties of NiFe/CoO, NiFe/α-Fe2O3 bilayers, and NiFe/CoO/α-Fe2O3 trilayer were studied comparatively. The microstructure and chemical composition were characterized. Temperature dependent magnetometry reveals increased irreversibility temperature in NiFe/CoO/α-Fe2O3 trilayer compared with NiFe/CoO bilayer. The magnetic hysteresis loops show that the exchange bias (Hex) and coercivity (Hc) depend strongly on the anisotropy of AF layer (CoO, α-Fe2O3 and CoO/α-Fe2O3). Our work shows that the AF1/AF2 interfacial interactions can be used effectively for tuning the exchange bias in FM/AF1/AF2 trilayers.

Clinical and Economic Implications of AF Related Stroke.

PubMed

Ali, Ali N; Abdelhafiz, Ahmed

2016-01-01

A major cause of morbidity and mortality among patients with atrial fibrillation (AF) relates to the increased risk of stroke. The burden of illness that AF imparts on stroke is likely to increase with our aging populations and increasingly sophisticated cardiac monitoring techniques. Understanding the clinical and economic differences between AF related ischaemic stroke and non-AF related stroke is important if we are to improve future cost effectiveness analyses of potential preventative treatments, but also to help educate clinical and policy decision makers on use or availability of treatments to prevent AF related stroke. In this article we review the existing evidence that highlights differences in the clinical characteristics and outcomes between AF and non-AF stroke, as well as differences in their economic impact and discuss ways to improve future economic analyses.

In permanent atrial fibrillation, PDE3 reduces force responses to 5‐HT, but PDE3 and PDE4 do not cause the blunting of atrial arrhythmias

PubMed Central

Schwarz, Simon; Ravens, Ursula; Knaut, Michael

2016-01-01

Abstract Background and Purpose 5‐HT increases force and L‐type Ca2 + current (ICa,L) and causes arrhythmias through 5‐HT4 receptors in human atrium. In permanent atrial fibrillation (peAF), atrial force responses to 5‐HT are blunted, arrhythmias abolished but ICa,L responses only moderately attenuated. We investigated whether, in peAF, this could be due to an increased function of PDE3 and/or PDE4, using the inhibitors cilostamide (300 nM) and rolipram (1 μM) respectively. Experimental Approach Contractile force, arrhythmic contractions and ICa,L were assessed in right atrial trabeculae and myocytes, obtained from patients with sinus rhythm (SR), paroxysmal atrial fibrillation (pAF) and peAF. Key Results Maximum force responses to 5‐HT were reduced to 15% in peAF, but not in pAF. Cilostamide, but not rolipram, increased both the blunted force responses to 5‐HT in peAF and the inotropic potency of 5‐HT fourfold to sevenfold in trabeculae of patients with SR, pAF and peAF. Lusitropic responses to 5‐HT were not decreased in peAF. Responses of ICa,L to 5‐HT did not differ and were unaffected by cilostamide or rolipram in myocytes from patients with SR or peAF. Concurrent cilostamide and rolipram increased 5‐HT's propensity to elicit arrhythmias in trabeculae from patients with SR, but not with peAF. Conclusions and Implications PDE3, but not PDE4, reduced inotropic responses to 5‐HT in peAF, independently of lusitropy and ICa,L, but PDE3 activity was the same as that in patients with SR and pAF. Atrial remodelling in peAF abolished the facilitation of 5‐HT to induce arrhythmias by inhibition of PDE3 plus PDE4. PMID:27238373

Effect of Omega-3 Polyunsaturated Fatty Acid Supplementation in Patients with Atrial Fibrillation.

PubMed

Kumar, Sanjay; Qu, Sarah; Kassotis, John T

2012-01-01

Atrial fibrillation (AF) is the most common sustained atrial arrhythmia conferring a higher morbidity and mortality. Despite the increasing incidence of AF; available therapies are far from perfect. Dietary fish oils, containing omega 3 fatty acids, also called polyunsaturated fatty acid [PUFA] have demonstrated beneficial electrophysiological, autonomic and anti-inflammatory effects on both atrial and ventricular tissue. Multiple clinical trials, focusing on various subsets of patients with AF, have studied the role of PUFA and their potential role in reducing the incidence of this common arrhythmia. While PUFA appears to have a beneficial effect in the primary prevention of AF in the elderly with structural heart disease, this benefit has not been universally observed. In the secondary prevention of AF, PUFA seems to have a greater impact in the reducing AF in patients with paroxysmal or persistent AF, stages of AF associated with less atrial fibrosis and negative structural remodeling. However, AF suppression has not been consistently demonstrated in clinical trials. In patients undergoing heart surgery, increasing PUFA intake has yielded mixed results in terms of AF prevention post-operatively; however, increased PUFA has been associated with a reduction in hospital stay. Therefore recommending the use of PUFA for the purpose of AF reduction remains controversial. This is in part attributable to the complexity of AF. Other conflicting variables include: heterogeneous patient populations studied; variable dosing; duration of follow-up; comorbidities; and, concomitant pharmacotherapy. This review article reviews in detail available basic and clinical research studies of fish oil in the treatment of AF, and its role in the treatment of this common disorder. AF=Atrial fibrillation, CHS=Cardiovascular Health Study,CABG=Coronary artery bypass surgery, d=Day, DHA=Docosahexaenoic acid, EPA=Eicosapentaenoic acid, ERP= Effective refractory period, g=Gram, PAF= Paroxysmal atrial fibrillation, PeAF= Persistent atrial fibrillation PUFA= Polyunsaturated fatty acid.

Drosophila Fragile X Mental Retardation Protein Developmentally Regulates Activity-Dependent Axon Pruning

PubMed Central

Tessier, Charles R.; Broadie, Kendal

2014-01-01

Summary Fragile X Syndrome (FraX) is a broad-spectrum neurological disorder with symptoms ranging from hyperexcitability to mental retardation and autism. Loss of the fragile X mental retardation 1 (fmr1) gene product, the mRNA-binding translational regulator FMRP, causes structural over-elaboration of dendritic and axonal processes as well as functional alterations in synaptic plasticity at maturity. It is unclear, however, whether FraX is primarily a disease of development, a disease of plasticity or both; a distinction vital for engineering intervention strategies. To address this critical issue, we have used the Drosophila FraX model to investigate the developmental roles of Drosophila FMRP (dFMRP). dFMRP expression and regulation of chickadee/profilin coincides with a transient window of late brain development. During this time, dFMRP is positively regulated by sensory input activity, and required to limit axon growth and for efficient activity-dependent pruning of axon branches in the Mushroom Body learning/memory center. These results demonstrate that dFMRP has a primary role in activity-dependent neural circuit refinement in late brain development. PMID:18321984

A CGG-repeat expansion mutation in ZNF713 causes FRA7A: association with autistic spectrum disorder in two families.

PubMed

Metsu, Sofie; Rainger, Jacqueline K; Debacker, Kim; Bernhard, Birgitta; Rooms, Liesbeth; Grafodatskaya, Daria; Weksberg, Rosanna; Fombonne, Eric; Taylor, Martin S; Scherer, Stephen W; Kooy, R Frank; FitzPatrick, David R

2014-11-01

We report de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG-repeat expansion mutation (∼450 repeats) in a 5' intron of ZNF713. This expanded allele showed hypermethylation of the adjacent CpG island with reduced ZNF713 expression observed in a proband-derived lymphoblastoid cell line (LCL). His unaffected mother carried an unmethylated premutation (85 repeats). This CGG-repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. ZNF713 expression in LCLs in this family was increased in three of these four premutation carriers. A firm link cannot yet be established between ASD and the repeat expansion mutation but plausible pathogenic mechanisms are discussed. © 2014 WILEY PERIODICALS, INC.

First-line antituberculosis drug, pyrazinamide, its pharmaceutically relevant cocrystals and a salt.

PubMed

Sarmah, Kashyap Kumar; Rajbongshi, Trishna; Bhowmick, Sourav; Thakuria, Ranjit

2017-10-01

A few pyrazinamide (Pyz) cocrystals involving hydroxybenzoic/cinnamic acid derivatives [2,4-dihydroxybenzoic acid (24DHBA); 2,6-dihydroxybenzoic acid (26DHBA); 3,5-dihydroxybenzoic acid (35DHBA) and nutraceutical molecule ferulic acid (FRA)] and the first example of a molecular salt with p-toluenesulfonic acid (pTSA) have been prepared and characterized using various solid-state techniques. A high-temperature cocrystal polymorph of Pyz·FRA has been characterized from the endothermic peaks observed using differential scanning calorimetry. The presence of substituent groups carrying hydrogen bond donors or acceptors and their influence on supramolecular synthon formation has been investigated using a Cambridge Structural Database search. Equilibrium solubility of all the binary complexes of Pyz follows the order of their coformer solubility, i.e. Pyz + ·pTSA - > Pyz·35DHBA > Pyz > Pyz·26DHBA > Pyz·24DHBA > Pyz·FRA. A twofold enhancement in solubility of Pyz + ·pTSA - molecular salt compared with the parent drug suggests a potential drug formulation for the treatment of tuberculosis.

Photosynthesis Is Not Involved in the Mechanism of Action of Acifluorfen in Cucumber (Cucumis sativus L.)

PubMed Central

Duke, Stephen O.; Kenyon, William H.

1986-01-01

The possible role of photosynthesis in the mechanism of action of the herbicide acifluorfen (2-chloro-4-(trifluoromethyl)phenoxy-2-nitrobenzoate; AF) was examined. The sensitivity to AF of cotyledons of cucumber (Cucumis sativus L.) which had been grown under far red light (FR) and white light were compared. FR grown tissues which were photosynthetically imcompetent were hypersensitive to AF under white light and had approximately the same relative response to AF under blue and red light as green, white-light-grown tissues. Ultrastructural damage was apparent in FR-grown, AF-treated tissues within an hour after exposure to white light, with cytoplasmic and plastidic disorganization occurring simultaneously. In cucumber cotyledon tissue which had been greening for various time periods, there was no correlation between photosynthetic capacity and herbicidal efficacy of AF. PSII inhibitors (atrazine and DCMU) and the photophosphorylation inhibitor, tentoxin, had no effect on AF activity. Atrazine did not reduce AF activity at any concentration or light intensity tested, indicating that there is no second, photosynthetic-dependent mechanism of action operating at low AF concentrations or low fluence rates. Carbon dioxide-dependent O2 evolution of intact chloroplasts of spinach (Spinacia oleracea L.) had an AF I50 of 125 micromolar compared to 1000 micromolar for cucumber, whereas AF was much more herbicidally active in tissues of cucumber than of spinach. Differences in activity could not be accounted for by differences in uptake of AF. Our results indicate that there is no photosynthetic involvement in the mechanism of action of AF in cucumber. Images Fig. 2 PMID:16664919

Prospective study of atrial fibrillation termination during ablation guided by automated detection of fractionated electrograms.

PubMed

Porter, Michael; Spear, William; Akar, Joseph G; Helms, Ray; Brysiewicz, Neil; Santucci, Peter; Wilber, David J

2008-06-01

Complex fractionated atrial electrograms (CFAE) may identify critical sites for perpetuation of atrial fibrillation (AF) and provide useful targets for ablation. Current assessment of CFAE is subjective; automated detection algorithms may improve reproducibility, but their utility in guiding ablation has not been tested. In 67 patients presenting for initial AF ablation (42 paroxysmal, 25 persistent), LA and CS mapping were performed during induced or spontaneous AF. CFAE were identified by an online automated computer algorithm and displayed on electroanatomical maps. A mean of 28 +/- 18 sites/patient were identified (20 +/- 13% of mapped sites), and were more frequent during persistent AF. CFAE occurred most commonly within the CS, on the atrial septum, and around the pulmonary veins. Ablation initially targeting CFAE terminated AF in 88% of paroxysmal AF, but only 20% of persistent AF (P < 0.001). Subsequently, additional ablation was performed in all patients (PV isolation for paroxysmal AF, PV isolation + mitral and roof lines for persistent AF). Minimum follow-up was 1 year. One-year freedom from recurrent atrial arrhythmias without antiarrhythmic drug therapy after a single procedure was 90% for paroxysmal AF, and 68% for persistent AF. Ablation guided by automated detection of CFAE proved feasible, and was associated with a high AF termination rate in paroxysmal, but not persistent AF. As an adjunct to conventional techniques, it was associated with excellent long-term single procedure outcomes in both groups. Criteria for identifying optimal CFAE sites for ablation, and selection of patients most likely to benefit, require additional study.

Clinical presentation, management, and outcomes in the Indian Heart Rhythm Society-Atrial Fibrillation (IHRS-AF) registry.

PubMed

Vora, A; Kapoor, A; Nair, M; Lokhandwala, Y; Narsimhan, C; Ravikishore, A G; Dwivedi, S K; Namboodiri, N; Hygriv, R; Saxena, A; Nabar, A; Garg, S; Bardoloi, N; Yadav, R; Nambiar, A; Pandurangi, U; Jhala, D; Naik, A; Nagmallesh; Rajagopal, S; Selvaraj, R; Arora, V; Thachil, A; Thomas, J; Panicker, G

A national atrial fibrillation (AF) registry was conducted under the aegis of the Indian Heart Rhythm Society (IHRS), to capture epidemiological data-type of AF, clinical presentation and comorbidities, current treatment practices, and 1-year follow-up outcomes. A total of 1537 patients were enrolled from 24 sites in India in the IHRS-AF registry from July 2011 to August 2012. Their baseline characteristics and follow-up data were recorded in case report forms and subsequently analyzed. The average age of Indian AF patients was 54.7 years. There was a marginal female preponderance - 51.5% females and 48.5% males. At baseline, 20.4% had paroxysmal AF; 33% had persistent AF; 35.1% had permanent AF and 11% had first AF episode. At one-year follow-up, 45.6% patients had permanent AF. Rheumatic valvular heart disease (RHD) was present in 47.6% of patients. Hypertension, heart failure, coronary artery disease, and diabetes were seen in 31.4%, 18.7%, 16.2%, and 16.1%, respectively. Rate control was the strategy used in 75.2% patients, digoxin and beta-blockers being the most frequently prescribed rate-control drugs. Oral anticoagulation (OAC) drugs were used in 70% of patients. The annual mortality was 6.5%, hospitalization 8%, and incidence of stroke 1%. In India, AF patients are younger and RHD is still the most frequent etiology. Almost two-third of the patients have persistent/permanent AF. At one-year follow-up, there is a significant mortality and morbidity in AF patients in India. Copyright © 2016. Published by Elsevier B.V.

Successful Repeat Catheter Ablation of Recurrent Longstanding Persistent Atrial Fibrillation With Rotor Elimination as the Procedural Endpoint: A Case Series.

PubMed

Sommer, Philipp; Kircher, Simon; Rolf, Sascha; John, Silke; Arya, Arash; Dinov, Borislav; Richter, Sergio; Bollmann, Andreas; Hindricks, Gerhard

2016-03-01

There remains a lack of consensus regarding the ideal ablation strategy for atrial fibrillation (AF), particularly in patients with persistent or longstanding persistent AF. Given increasing evidence from clinical imaging studies that rotors sustain AF, rotor elimination may be a desirable procedural endpoint. However, there is no description to date of the clinical outcomes using rotor elimination during ablation as the procedural endpoint. Moreover, a series of studies question whether procedural AF termination is a desirable endpoint for ablation after many forms of AF ablation. We report a single-center experience of rotor elimination during AF ablation using Focal Impulse and Rotor Mapping (FIRM), describing 20 consecutive patients with case descriptions of 3 patients with recurrent longstanding persistent AF after prior ablation. In all cases, endocardial mapping using a 64-electrode basket catheter was performed to identify rotors, which were eliminated using radiofrequency catheter ablation. After it was verified that all identified rotors were eliminated, standard ablation consisting of PV isolation was performed. Notably, persistent AF terminated in only 1/20 (5%) patients. However, after a follow-up of 6 months, single-procedure freedom from AF was 80% (16/20 patients) with only 1 patient on antiarrhythmic drugs. All three patients in the highlighted series are AF free despite the lack of acute procedural AF termination. Patients with persistent AF including those with unsuccessful prior ablation can be treated successfully by rotor targeted ablation, using the elimination of all rotors rather than acute AF termination as the procedural endpoint. © 2015 Wiley Periodicals, Inc.

Continuous ECG monitoring for tracking down atrial fibrillation after stroke: Holter or automated analysis strategy?

PubMed

Suissa, Laurent; Lachaud, Sylvain; Mahagne, Marie-Hélène

2014-01-01

Tracking down atrial fibrillation (AF) in the stroke unit is a relevant challenge for the prevention of recurrent AF-related stroke. The optimal terms of use of continuous ECG monitoring (CEM) are unknown. We compared 24-hour routine Holter ECG with two different CEM analysis strategies for AF detection. We prospectively enrolled consecutive ischemic stroke patients. All AF-naïve patients received CEM during hospitalization. Two methods for reading CEM data were compared: manual analysis using the Holter function (hCEM) and semiautomated analysis using software (aCEM). The McNemar test was used to compare AF detection rates. Of the 362 patients included, 58 (16.0%) were non-AF-naïve patients and 304 were AF-naïve patients. AF-Naïve patients underwent CEM with a median duration of 5.3 days (3.4-9.7). We detected 22 new AF cases (7.2%) with first-24-hour hCEM, 31 (10.2%) with aCEM, and 42 (13.8%) with hCEM. hCEM and aCEM both significantly increased the AF detection rate compared to first-24-hour hCEM. hCEM detected more new AF cases than aCEM (+3.6%, p = 0.003). In stroke patients, early and prolonged aCEM and hCEM both increase the AF detection rate compared to first-24-hour hCEM. hCEM gives the best AF detection rate. We suggest that in aCEM, detection based only on the ventricular rhythm analysis explains its lower specificity and sensitivity. © 2014 S. Karger AG, Basel.

A structured reading algorithm improves telemetric detection of atrial fibrillation after acute ischemic stroke.

PubMed

Kallmünzer, Bernd; Breuer, Lorenz; Hering, Christiane; Raaz-Schrauder, Dorette; Kollmar, Rainer; Huttner, Hagen B; Schwab, Stefan; Köhrmann, Martin

2012-04-01

Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. Median effective telemetry monitoring time was 75.5 hours (interquartile range 64-86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

A systematic review of the health benefits of exercise rehabilitation in persons living with atrial fibrillation.

PubMed

Giacomantonio, Nicholas B; Bredin, Shannon S D; Foulds, Heather J A; Warburton, Darren E R

2013-04-01

This systematic review sought to evaluate critically the health benefits of physical activity among persons with atrial fibrillation (AF). AF is increasing in Western society. While health benefits of physical activity are well established, benefits of physical activity among individuals with AF are not clearly identified. Literature was retrieved systematically through searching electronic databases (MEDLINE, EMBASE, Cochrane), cross-referencing, and drawing on the authors' knowledge. Identified original research articles evaluated health benefits of physical activity among persons with AF or effects of physical activity on AF incidence. From 1056 individual citations, 36 eligible articles were identified. Moderate-intensity physical activity was found to improve exercise capacity, quality of life, and the ability to carry out activities of daily living among persons with AF (n = 6). Increased incidence of AF was not associated with physical activity among the general population (n = 2), although long-term vigorous endurance exercise may be associated with increased incidence of AF (n = 7), and greater risks may be associated with high-intensity physical activity among those with AF (n = 2). Moderate-intensity physical activity among individuals with AF does not adversely alter training outcomes, functional capacity, morbidity, or mortality compared with those in sinus rhythm (n = 12). Physical activity may improve management and treatment of AF (n = 6) and, among at-risk populations, may reduce incidence of AF (n = 3). In conclusion, moderate-intensity physical activity should be encouraged among persons with or at risk of AF. Further research is needed. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

PubMed Central

Pellman, Jason; Sheikh, Farah

2017-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca2+ current, various K+ currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. PMID:25880508

Lone atrial fibrillation: where are we now?

PubMed

Potpara, Tatjana S; Lip, Gregory Y

2011-10-01

There is a growing pandemic of atrial fibrillation (AF), affecting nearly 2% of the general adult population. Atrial fibrillation is commonly associated with structural heart disease, and AF itself causes a sequence of complex processes of electrical, contractile, and structural remodeling of the atrial myocardium, which facilitate further AF progression. Nonetheless, AF may also affect individuals aged ≤ 65 years who have no evidence of associated cardiopulmonary or other disease, including hypertension; this is otherwise referred to as "lone" AF and is considered to have a generally favorable prognosis. The true prevalence of lone AF is unknown. Growing insights into the diversity of numerous mechanisms involved in the pathogenesis of AF, including acute atrial stretch, structural and electrophysiological alterations, systemic inflammation, oxidative stress, autonomic imbalance, genetic predisposition, and many others, and increasing recognition of novel risk factors for AF, including obesity, metabolic syndrome, subclinical atherosclerosis, sleep apnea, alcohol consumption, and endurance sports, suggest that apparently lone AF might not be so "lone" in many patients, which could have important prognostic and therapeutic implications. In this article, we summarize the current knowledge of epidemiology, etiopathogenesis, and pathophysiology of so-called lone AF and discuss the issues of long-term prognosis and management of patients who have an apparently lone AF.

AF-6 is a positive modulator of the PINK1/parkin pathway and is deficient in Parkinson's disease

PubMed Central

Haskin, Joseph; Szargel, Raymonde; Shani, Vered; Mekies, Lucy N.; Rott, Ruth; Lim, Grace G. Y.; Lim, Kah-Leong; Bandopadhyay, Rina; Wolosker, Herman; Engelender, Simone

2013-01-01

Parkin E3 ubiquitin-ligase activity and its role in mitochondria homeostasis are thought to play a role in Parkinson's disease (PD). We now report that AF-6 is a novel parkin interacting protein that modulates parkin ubiquitin-ligase activity and mitochondrial roles. Parkin interacts with the AF-6 PDZ region through its C-terminus. This leads to ubiquitination of cytosolic AF-6 and its degradation by the proteasome. On the other hand, endogenous AF-6 robustly increases parkin translocation and ubiquitin-ligase activity at the mitochondria. Mitochondrial AF-6 is not a parkin substrate, but rather co-localizes with parkin and enhances mitochondria degradation through PINK1/parkin-mediated mitophagy. On the other hand, several parkin and PINK1 juvenile disease-mutants are insensitive to AF-6 effects. AF-6 is present in Lewy bodies and its soluble levels are strikingly decreased in the caudate/putamen and substantia nigra of sporadic PD patients, suggesting that decreased AF-6 levels may contribute to the accumulation of dysfunctional mitochondria in the disease. The identification of AF-6 as a positive modulator of parkin translocation to the mitochondria sheds light on the mechanisms involved in PD and underscores AF-6 as a novel target for future therapeutics. PMID:23393160

The Bcr Kinase Downregulates Ras Signaling by Phosphorylating AF-6 and Binding to Its PDZ Domain

PubMed Central

Radziwill, G.; Erdmann, R. A.; Margelisch, U.; Moelling, K.

2003-01-01

The protein kinase Bcr is a negative regulator of cell proliferation and oncogenic transformation. We identified Bcr as a ligand for the PDZ domain of the cell junction and Ras-interacting protein AF-6. The Bcr kinase phosphorylates AF-6, which subsequently allows efficient binding of Bcr to AF-6, showing that the Bcr kinase is a regulator of the PDZ domain-ligand interaction. Bcr and AF-6 colocalize in epithelial cells at the plasma membrane. In addition, Bcr, AF-6, and Ras form a trimeric complex. Bcr increases the affinity of AF-6 to Ras, and a mutant of AF-6 that lacks a specific phosphorylation site for Bcr shows a reduced binding to Ras. Wild-type Bcr, but not Bcr mutants defective in binding to AF-6, interferes with the Ras-dependent stimulation of the Raf/MEK/ERK pathway. Since AF-6 binds to Bcr via its PDZ domain and to Ras via its Ras-binding domain, we propose that AF-6 functions as a scaffold-like protein that links Bcr and Ras to cellular junctions. We suggest that this trimeric complex is involved in downregulation of Ras-mediated signaling at sites of cell-cell contact to maintain cells in a nonproliferating state. PMID:12808105

Rhythm-based heartbeat duration normalization for atrial fibrillation detection.

PubMed

Islam, Md Saiful; Ammour, Nassim; Alajlan, Naif; Aboalsamh, Hatim

2016-05-01

Screening of atrial fibrillation (AF) for high-risk patients including all patients aged 65 years and older is important for prevention of risk of stroke. Different technologies such as modified blood pressure monitor, single lead ECG-based finger-probe, and smart phone using plethysmogram signal have been emerging for this purpose. All these technologies use irregularity of heartbeat duration as a feature for AF detection. We have investigated a normalization method of heartbeat duration for improved AF detection. AF is an arrhythmia in which heartbeat duration generally becomes irregularly irregular. From a window of heartbeat duration, we estimate the possible rhythm of the majority of heartbeats and normalize duration of all heartbeats in the window based on the rhythm so that we can measure the irregularity of heartbeats for both AF and non-AF rhythms in the same scale. Irregularity is measured by the entropy of distribution of the normalized duration. Then we classify a window of heartbeats as AF or non-AF by thresholding the measured irregularity. The effect of this normalization is evaluated by comparing AF detection performances using duration with the normalization, without normalization, and with other existing normalizations. Sensitivity and specificity of AF detection using normalized heartbeat duration were tested on two landmark databases available online and compared with results of other methods (with/without normalization) by receiver operating characteristic (ROC) curves. ROC analysis showed that the normalization was able to improve the performance of AF detection and it was consistent for a wide range of sensitivity and specificity for use of different thresholds. Detection accuracy was also computed for equal rates of sensitivity and specificity for different methods. Using normalized heartbeat duration, we obtained 96.38% accuracy which is more than 4% improvement compared to AF detection without normalization. The proposed normalization method was found useful for improving performance and robustness of AF detection. Incorporation of this method in a screening device could be crucial to reduce the risk of AF-related stroke. In general, the incorporation of the rhythm-based normalization in an AF detection method seems important for developing a robust AF screening device. Copyright © 2016 Elsevier Ltd. All rights reserved.

Advancing the literature on designing audit and feedback interventions: identifying theory-informed hypotheses.

PubMed

Colquhoun, Heather L; Carroll, Kelly; Eva, Kevin W; Grimshaw, Jeremy M; Ivers, Noah; Michie, Susan; Sales, Anne; Brehaut, Jamie C

2017-09-29

Audit and feedback (A&F) is a common strategy for helping health providers to implement evidence into practice. Despite being extensively studied, health care A&F interventions remain variably effective, with overall effect sizes that have not improved since 2003. Contributing to this stagnation is the fact that most health care A&F interventions have largely been designed without being informed by theoretical understanding from the behavioral and social sciences. To determine if the trend can be improved, the objective of this study was to develop a list of testable, theory-informed hypotheses about how to design more effective A&F interventions. Using purposive sampling, semi-structured 60-90-min telephone interviews were conducted with experts in theories related to A&F from a range of fields (e.g., cognitive, health and organizational psychology, medical decision-making, economics). Guided by detailed descriptions of A&F interventions from the health care literature, interviewees described how they would approach the problem of designing improved A&F interventions. Specific, theory-informed hypotheses about the conditions for effective design and delivery of A&F interventions were elicited from the interviews. The resulting hypotheses were assigned by three coders working independently into themes, and categories of themes, in an iterative process. We conducted 28 interviews and identified 313 theory-informed hypotheses, which were placed into 30 themes. The 30 themes included hypotheses related to the following five categories: A&F recipient (seven themes), content of the A&F (ten themes), process of delivery of the A&F (six themes), behavior that was the focus of the A&F (three themes), and other (four themes). We have identified a set of testable, theory-informed hypotheses from a broad range of behavioral and social science that suggest conditions for more effective A&F interventions. This work demonstrates the breadth of perspectives about A&F from non-healthcare-specific disciplines in a way that yields testable hypotheses for healthcare A&F interventions. These results will serve as the foundation for further work seeking to set research priorities among the A&F research community.

Rabbit notochordal cells modulate the expression of inflammatory mediators by human annulus fibrosus cells cocultured with activated macrophage-like THP-1 cells.

PubMed

Kim, Joo Han; Moon, Hong Joo; Lee, Jin Hoon; Kim, Jong Hyun; Kwon, Taek Hyun; Park, Youn Kwan

2012-10-15

We evaluated the influence of rabbit notochordal cells on the expression of inflammatory mediators by human annulus fibrosus (AF) cells cocultured with macrophage-like cells. To identify the protective effect of rabbit notochordal cells on AF during in vitro inflammation. Discogenic pain, which is an important cause of intractable lower back pain, is associated with macrophage-mediated inflammation in the AF. Although rabbit notochordal cells prevent intervertebral disc degeneration, their effects on human AF inflammation remain unknown. Human AF pellets were cocultured for 48 hours with notochordal cell clusters from adult New Zealand White rabbits and phorbol myristate acetate (PMA)-stimulated human macrophage-like THP-1 cells. Conditioned media (CM) from the cocultures were assayed by enzyme-linked immunosorbent assay. The expression of inflammatory mediators in the AF pellets was evaluated by real-time reverse-transcription polymerase chain reaction. The levels of mRNA for interleukin (IL)-6, IL-8, and inducible nitric oxide synthase (iNOS) in the AF pellets cocultured with notochordal cells and macrophages (hAF[rNC-M]) were significantly lower than those in the AF pellets cultured with macrophages alone (hAF[M]) (P < 0.05). The levels of IL-6 and IL-8 proteins in the CM of hAF(rNC-M) were significantly lower than those in the CM of hAF(M) (P < 0.05). Coculturing with notochordal cells significantly decreased the levels of mRNA for IL-6, IL-8, and iNOS in the macrophage-exposed AF pellets (P < 0.05). After 1 ng/mL IL-1β stimulation, the levels of IL-6 and IL-8 mRNA and the level of IL-8 protein production were significantly decreased in the AF pellets with notochordal cells compared with naïve AF pellets (P < 0.05). In an in vitro coculture system, rabbit notochordal cells reduced the levels of main inflammatory mediators and gene expression in the human AF during inflammation. Therefore, rabbit notochordal cells may constitute an important protective tool against symptomatic disc development.

Chemistry of 1,1,2,2,9,9,10,10-octafluoro-[2,2]-paracyclophane: Its synthesis and reactions

NASA Astrophysics Data System (ADS)

Duan, Jian-Xin

This dissertation describes the first example of the synthesis of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane (AF4) under non-high-dilution conditions. Under very mild reaction conditions, bis-p-(chlorodifluoromethyl)benzene (TFPX dichloride) and its derivatives reacted with Zn dust in N,N-dimethyl acetamide (DMA) (Zinc method) affording the corresponding AF4 and its derivatives in moderate to good yields. Purification of products was also studied and an efficient purification process was developed. A new and very cheap method for preparation of TFPX dichloride is also disclosed. Using the very cheap fluorinating reagent, anhydrous hydrogen fluoride (AHF), 1,4-bis(trichloromethyl)benezene or its derivatives were converted to TFPX and its derivatives in high yields (F/Cl exchange reaction). With the success of the Zinc method and F/Cl exchange reaction, highly pure AF4 thus can be provided to the semiconductor industry and academy research scientists in large quantity and at a very low price. Starting from AF4, numerous AF4 derivatives were synthesized using convenient reaction conditions. Reaction of AF4 with fuming nitric acid at room temperature gave mono-nitroAF4 in almost quantitative yield. Reduction of the mono-nitroAF4 with iron powder in the presence of HCl in alcoholic solvent gave the aminoAF4 in 90% yield. Via the diazonium salt intermediate, iodoAF4 was also obtained in good yield. Under similar reaction conditions, disubstituted AF4 derivatives were also prepared in good yields. Heating a mixture of AF4, trifluoroacetyl peroxide and dichloromethane gave the trifluoromethylated dimeric AF4 as a mixture of diastereomers. When these products were heated to 170--180°C in the presence of I 2, 4-trifluoromethyl-AF4 was obtained in almost 87% yield. X-ray structural analysis showed that the C-C bond connecting the two cyclophane moieties to be longer than the normal C-C bond. Kinetic studies, conducted in the presence of excess amount of hydrogen donor, showed this bond to be quite weak. Oxidation of AF4 with HIO3 in the presence of catalytic amount of H2SO4 in trifluoroacetic acid gave AF4 quinone in one step. AF4 quinone can be easily reduced to the hydroquinone by Na 2S2O4 aqueous solution.

Porous silicon photoluminescence biosensor for rapid and sensitive detection of toxins

NASA Astrophysics Data System (ADS)

Melnyk, Yulia; Pavlova, Karyna; Myndrul, Valerii; Viter, Roman; Smyntyna, Valentyn; Iatsunskyi, Igor

2017-08-01

A rapid and low cost photoluminescence (PL) immunosensor for the determination of low concentrations of Ochratoxin A(OTA) and Aflatoxine B1 (AfB1) has been developed. This biosensor was based on porous silicon (PSi) fabricated by metal-assisted chemical etching (MACE) and modified by antibodies against OTA/AfB1 (anti-OTA/anti-AfB1). Biofunctionalization method of the PSi surface by anti-OTA/ anti-AfB1 was developed. The changes of the PL intensity after interaction of the immobilized anti-OTA/anti-AfB1with OTA/AfB1 antigens were used as biosensor signal, allowing sensitive and selective detection of OTA/AfB1 antigens in BSA solution. The sensitivity of the reported optical biosensor towards OTA/AfB1 antigens is in the range from 10-3 to 102 ng/ml.

Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48

PubMed Central

Gupta, Deepak K.; Shah, Amil M.; Giugliano, Robert P.; Ruff, Christian T.; Antman, Elliott M.; Grip, Laura T.; Deenadayalu, Naveen; Hoffman, Elaine; Patel, Indravadan; Shi, Minggao; Mercuri, Michele; Mitrovic, Veselin; Braunwald, Eugene; Solomon, Scott D.

2014-01-01

Aims The complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF. Methods and results Left atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF (R = −0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography. Conclusions In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients. Clinical Trial Registration: http://www.clinicaltrials.gov; ID = NCT00781391. PMID:24302269

The why, when and how to test for obstructive sleep apnea in patients with atrial fibrillation.

PubMed

Desteghe, Lien; Hendriks, Jeroen M L; McEvoy, R Doug; Chai-Coetzer, Ching Li; Dendale, Paul; Sanders, Prashanthan; Heidbuchel, Hein; Linz, Dominik

2018-04-12

Sleep apnea is associated with increased cardiovascular risk and may be important in atrial fibrillation (AF) management. It is present in up to 62% of the AF population and is highly under-recognized and underdiagnosed. Obstructive sleep apnea (OSA) is strongly associated with AF and non-randomized trials have shown that its treatment can help to reduce AF recurrences and maintain sinus rhythm. The 2016 European Society of Cardiology guidelines for the management of AF recommend that AF patients should be questioned regarding the symptoms of OSA and that OSA-treatment should be optimized to improve AF treatment results. However, strategies on how to implement OSA testing in the standard work-up of AF patients are not provided in the guidelines. Additionally, overnight OSA monitoring rather than interrogation for OSA-related clinical signs alone may be necessary to reliably identify OSA in the majority of AF patients. This review summarizes the available clinical data on OSA in AF patients, and discusses the following key questions: Why and When is testing for OSA needed in AF patients? How and Where should it be performed and coordinated? and Who should test for OSA? To implement OSA testing in a cardiology or electrophysiology clinic, we propose a multidisciplinary integrated care approach based on a chronic care model. We describe the tools, infrastructure and coordination needed to test for OSA in the standard workup of patients with symptomatic AF prior to the initiation of directed invasive or pharmacological rhythm control management.

Determination of trace cadmium in rice by liquid spray dielectric barrier discharge induced plasma - chemical vapor generation coupled with atomic fluorescence spectrometry

NASA Astrophysics Data System (ADS)

Liu, Xing; Zhu, Zhenli; Bao, Zhengyu; Zheng, Hongtao; Hu, Shenghong

2018-03-01

Cadmium contamination in rice has become an increasing concern in many countries including China. A simple, cost-effective, and highly sensitive method was developed for the determination of trace cadmium in rice samples based on a new high-efficient liquid spray dielectric barrier discharge induced plasma (LSDBD) vapor generation coupled with atomic fluorescence spectrometry (AFS). The analytical procedure involves the efficient formation of Cd volatile species by LSDBD plasma induced chemical processes without the use of any reducing reagents (Na/KBH4 in conventional hydride generation). The effects of the addition of organic substances, different discharge parameters such as discharge voltage and discharge gap, as well as the foreign ion interferences were investigated. Under optimized conditions, a detection limit of 0.01 μg L- 1 and a precision of 0.8% (RSD, n = 5, 1 μg L- 1 Cd) was readily achieved. The calibration curve was linear in the range between 0.1 and 10 μg L- 1, with a correlation coefficient of R2 = 0.9995. Compared with the conventional acid-BH4- vapor generation, the proposed method not only eliminates the use of unstable and expensive reagents, but also offers high tolerance for coexisting ions, which is well suited to the direct analysis of environmental samples. The validation of the proposed method was demonstrated by the analysis of Cd in reference material of rice (GBW080684). It was also successfully applied to the determination of trace cadmium in locally collected 11 rice samples, and the obtained Cd concentrations are ranged from 7.2 to 517.7 μg kg- 1.

Atrial fibrillation in the Middle East: unmapped, underdiagnosed, undertreated.

PubMed

Al-Shamkhani, Warkaa; Ayetey, Harold; Lip, Gregory Y H

2018-05-01

Atrial fibrillation (AF) is the commonest persistent cardiac arrhythmia with an estimated incidence rate of between 1.5-2% and an important cause of strokes. Few epidemiological studies and clinical trials on the management of AF have been conducted outside Europe and North America. These gaps in our understanding of AF likely lead to sub-optimal management of patients with AF in the rest of the world. Areas covered: We discuss the epidemiology, treatment and clinical outcomes for AF in the Middle East after systematic review of published work for AF from the Middle East. We also discuss important clinical trials on AF conducted in the West in the same period to help contextualize our findings. Expert commentary: The few available Middle East studies suggest important epidemiological differences between Middle Eastern and Western AF populations. In particular, the Middle Eastern AF population is younger and have more co-morbidities than patients in the West. We find that significant numbers of moderate to high risk patients with AF are either undertreated or untreated placing them at increased risk of complications such as stroke. More studies in the Middle Eastern population are required to aid the development of region-specific clinical guidelines to improve patient care.

Persistent atrial fibrillation vs paroxysmal atrial fibrillation: differences in management.

PubMed

Margulescu, Andrei D; Mont, Lluis

2017-08-01

Atrial fibrillation (AF) is the most common human arrhythmia. AF is a progressive disease, initially being nonsustained and induced by trigger activity, and progressing towards persistent AF through alteration of the atrial myocardial substrate. Treatment of AF aims to decrease the risk of stroke and improve the quality of life, by preventing recurrences (rhythm control) or controlling the heart rate during AF (rate control). In the last 20 years, catheter-based and, less frequently, surgical and hybrid ablation techniques have proven more successful compared with drug therapy in achieving rhythm control in patients with AF. However, the efficiency of ablation techniques varies greatly, being highest in paroxysmal and lowest in long-term persistent AF. Areas covered: In this review, we discuss the fundamental differences between paroxysmal and persistent AF and the potential impact of those differences on patient management, emphasizing the available therapeutic strategies to achieve rhythm control. Expert commentary: Treatment to prevent AF recurrences is suboptimal, particularly in patients with persistent AF. Emerging technologies, such as documentation of atrial fibrosis using magnetic resonance imaging and documentation of electrical substrate using advanced electrocardiographic imaging techniques are likely to provide valuable insights about patient-specific tailoring of treatments.

Management of recent-onset sustained atrial fibrillation: pharmacologic and nonpharmacologic strategies.

PubMed

Lau, Dennis H; Kalman, Jonathan; Sanders, Prashanthan

2014-09-01

Recent studies have highlighted significant variations in the management of recent-onset sustained atrial fibrillation (AF). We aim to provide a succinct and clear management algorithm for physicians treating patients with recent-onset sustained AF. We performed a comprehensive search of the literature on the management of recent-onset sustained AF with focus on studies reporting cardioversion of AF, antiarrhythmic agents, and anticoagulation. We also reviewed recent practice guidelines on AF management. This review provides a guide on a tailored management approach of patients with recent-onset sustained AF. After initial detailed clinical assessment, optimal rate and rhythm control options can be provided, depending on hemodynamic stability, duration of AF episode, and AF stroke risk. Issues surrounding electrical and pharmacologic cardioversion are discussed in detail. We emphasize the importance of thromboembolic risk assessment and appropriate anticoagulation surrounding the point of cardioversion. Last, we highlighted the need for appropriate specialized follow-up care after acute AF management. Despite the highly heterogeneous clinical presentations, management of recent-onset sustained AF must include stroke risk assessment, appropriate anticoagulation, and follow-up care in all patients beyond optimum rate and rhythm control strategies. Copyright © 2014. Published by Elsevier Inc.

Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival

PubMed Central

Fei, Dennis Liang; Motowski, Hayley; Chatrikhi, Rakesh; Gao, Shaojian; Kielkopf, Clara L.; Varmus, Harold

2016-01-01

We have asked how the common S34F mutation in the splicing factor U2AF1 regulates alternative splicing in lung cancer, and why wild-type U2AF1 is retained in cancers with this mutation. A human lung epithelial cell line was genetically modified so that U2AF1S34F is expressed from one of the two endogenous U2AF1 loci. By altering levels of mutant or wild-type U2AF1 in this cell line and by analyzing published data on human lung adenocarcinomas, we show that S34F-associated changes in alternative splicing are proportional to the ratio of S34F:wild-type gene products and not to absolute levels of either the mutant or wild-type factor. Preferential recognition of specific 3′ splice sites in S34F-expressing cells is largely explained by differential in vitro RNA-binding affinities of mutant versus wild-type U2AF1 for those same 3′ splice sites. Finally, we show that lung adenocarcinoma cell lines bearing U2AF1 mutations do not require the mutant protein for growth in vitro or in vivo. In contrast, wild-type U2AF1 is required for survival, regardless of whether cells carry the U2AF1S34F allele. Our results provide mechanistic explanations of the magnitude of splicing changes observed in U2AF1-mutant cells and why tumors harboring U2AF1 mutations always retain an expressed copy of the wild-type allele. PMID:27776121

10-year nationwide trends of the incidence, prevalence, and adverse outcomes of non-valvular atrial fibrillation nationwide health insurance data covering the entire Korean population.

PubMed

Kim, Daehoon; Yang, Pil-Sung; Jang, Eunsun; Yu, Hee Tae; Kim, Tae-Hoon; Uhm, Jae-Sun; Kim, Jong-Youn; Pak, Hui-Nam; Lee, Moon-Hyoung; Joung, Boyoung; Lip, Gregory Yh

2018-05-01

Most data on the clinical epidemiology of atrial fibrillation (AF) are reported from Western populations, and data for Asians are limited. We aimed to investigate the 10-year trends of the prevalence and incidence of non-valvular AF and provide prevalence projections till 2060 in Korea. We also investigated the annual risks of adverse outcomes among patients with AF. Using the Korean National Health Insurance Service database involving the entire Korean population, a total of 679,416 adults with newly diagnosed AF were identified from 2006 to 2015. The incidence and prevalence of AF and risk of adverse outcomes following AF onset were assessed. The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015. The trend of its incidence was flat with a 10-year overall incidence of 1.77 per 1,000 person-years. The prevalence of AF is expected to reach 5.81% (2,290,591 patients with AF) in 2060. For a decade, the risk of all-cause mortality following AF declined by 30% (adjusted hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.68-0.72), heart failure by 52% (adjusted HR: 0.48, 95% CI: 0.44-0.51), and ischemic stroke by 9% (adjusted HR: 0.91, 95% CI: 0.88-0.93). The burden of AF among Asian patients is increasing. Although the overall risks of cardiovascular events and death following AF onset have decreased over a decade, the event rates are still high. Optimized management of any associated comorbidities should be part of the holistic management approach for patients with AF. Copyright © 2018. Published by Elsevier Inc.