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Sample records for af cancer recti

  1. Diastasis recti

    MedlinePlus

    ... Call your health care provider right away if a child with diastasis recti: Develops redness or pain in the ... wall, umbilicus, peritoneum, mesenteries, omentum, and retroperitoneum. In: Townsend CM Jr, Beauchamp RD, Evers BM, Mattox KL, ...

  2. Bile acid transformations by Alcaligenes recti.

    PubMed

    Mazumder, I; Mahato, S B

    1993-02-01

    Metabolism of cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid by the grown cells of the bacterium Alcaligenes recti suspended in water was studied. Each isolated metabolite was characterized by the application of various spectroscopic methods. Cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid yielded methylated derivatives 3 alpha-methoxy-7 alpha, 12 alpha-dihydroxy-5 beta-cholanoic acid, 3 alpha-methoxy-7 alpha-hydroxy-5 beta-cholanoic acid, 3 alpha-methoxy-7 beta-hydroxy-5 beta-cholanoic acid, and 3 alpha-methoxy-12 alpha-hydroxy-5 beta-cholanoic acid, respectively. In addition, cholic acid furnished 7 alpha, 12 alpha-dihydroxy-3-oxochol-4-en-24-oic acid; chenodeoxycholic acid gave 7 alpha-hydroxy-3-oxo-5 beta-cholanoic acid and 7 alpha-hydroxy-3-oxochol-4-en-24-oic acid while ursodeoxycholic acid yielded 7 beta-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid. The formation of various metabolites showed that two competitive enzymic reactions, i.e., selective methylation of the 3 alpha-hydroxy group and dehydrogenation in the A/B rings, were operative. The methylation process was found to be enzymic involving an S-adenosyl-L-methionine (AdoMet)-dependent methyl transferase, and this reaction appeared to be inhibitory to the process of degradation of the ring system. In the other reaction sequence, degradation of the ring system was initiated by dehydrogenation of the 3 alpha-hydroxy group. A 7 beta-dehydratase activity producing the delta 6 double bond was also noticeable in the metabolism of ursodeoxycholic acid. PMID:8484188

  3. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

    PubMed

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D; Moriggl, Richard; Kenner, Lukas; Tse, William

    2015-08-21

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties. PMID:26079538

  4. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis

    PubMed Central

    Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T.; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bago-Horvath, Zsuzsanna; Gibson, Laura F.; Rojanasakul, Yon; Remick, Scot; Ivanov, Alexey; Pugacheva, Elena; Bunting, Kevin D.; Moriggl, Richard

    2015-01-01

    AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent “metastatic founder cells” which have invasive properties. PMID:26079538

  5. E1AF/PEA3 activates the Rho/Rho-associated kinase pathway to increase the malignancy potential of non-small-cell lung cancer cells.

    PubMed

    Hakuma, Nobuyuki; Kinoshita, Ichiro; Shimizu, Yasushi; Yamazaki, Koichi; Yoshida, Koichi; Nishimura, Masaharu; Dosaka-Akita, Hirotoshi

    2005-12-01

    E1AF/PEA3, an Ets family transcription factor, is frequently overexpressed in non-small-cell lung cancers (NSCLCs). Overexpression of E1AF increases motility and invasion of VMRC-LCD and NCI-H226 NSCLC cells, which lack endogenous E1AF expression, and the effect is synergistically increased by hepatocyte growth factor (HGF). The small GTPase Rho/Rho-associated kinase (ROCK) pathway is also involved in motility and invasion. To determine the role of the Rho/ROCK pathway in malignant phenotypes induced by E1AF, we analyzed VMRC-LCD cells transfected with an E1AF expression vector (LCD-E1AF cells) or with empty vector (LCD-vector cells). LCD-E1AF cells had more GTP-bound (active) Rho than LCD-vector cells and Rho activation was synergistically increased by HGF. The Rho activation by E1AF and HGF was also shown in NCI-H226 cells. Phosphorylation of myosin light chain (MLC), a downstream effector of ROCK signaling, was higher in LCD-E1AF cells than in LCD-vector cells, especially under HGF treatment. A specific ROCK inhibitor, Y27632, strongly suppressed MLC phosphorylation, cell motility, and invasion. In nude mice implanted s.c. and intrapulmonarily, LCD-E1AF cells made more local tumors than LCD-vector cells (six of six versus one of seven mice and four of seven versus one of seven mice, respectively). Three of the four mice with lung tumors from LCD-E1AF cells had lymph node metastases whereas the mouse with LCD-vector tumors did not. LCD-E1AF tumors showed higher MLC phosphorylation than LCD-vector tumors. These results suggest that E1AF activates the Rho/ROCK pathway in an HGF-enhanced manner and its activation is important in E1AF-induced motility and invasion as well as tumorigenesis and metastasis in NSCLC cells. PMID:16322223

  6. Flavonoid-enriched apple fraction AF4 induces cell cycle arrest, DNA topoisomerase II inhibition, and apoptosis in human liver cancer HepG2 cells.

    PubMed

    Sudan, Sudhanshu; Rupasinghe, H P Vasantha

    2014-01-01

    Apples are a major source of dietary phytochemicals such as flavonoids in the Western diet. Here we report anticancer properties and possible mechanism of action of apple flavonoid-enriched fraction (AF4) isolated from the peels of Northern Spy apples in human hepatocellular carcinoma cells, HepG2. Treatment with AF4 induced cell growth inhibition in HepG2 cells in time- and dose-dependent manner. Concentration of 50 μg/ml (50 μg total monomeric polyphenols/ml) AF4 was sufficient to induce a significant reduction in cell viability within 6 h of treatment (92%, P < 0.05) but had very low toxicity (minimum 4% to maximum 16%) on primary liver and lung cells, which was significantly lower than currently prescribed chemotherapy drug Sorafenib (minimum 29% to maximum 49%, P < 0.05). AF4 induced apoptosis in HepG2 cells within 6 h of treatment via activation of caspase-3. Cell cycle analysis via flow-cytometer showed that AF4 induced G2/M phase arrest. Further, results showed that AF4 acts as a strong DNA topoisomerase II catalytic inhibitor, which may be a plausible reason to drive the cells to apoptosis. Overall, our data suggests that AF4 possesses a significantly stronger antiproliferative and specific action than Sorafenib in vitro and is a potential natural chemotherapy agent for treatment of liver cancer. PMID:25256427

  7. Evidence for impaired retinoic acid receptor-thyroid hormone receptor AF-2 cofactor activity in human lung cancer.

    PubMed Central

    Moghal, N; Neel, B G

    1995-01-01

    Retinoic acid (RA) is required for normal airway epithelial cell growth and differentiation both in vivo and in vitro. One of the earliest events following the exposure of bronchial epithelial cells to RA is the strong induction of RA receptor beta (RAR beta) mRNA. Previous work established that many lung cancer cell lines and primary tumors display abnormal RAR beta mRNA expression, most often absence or weak expression of the RAR beta 2 isoform, even after RA treatment. Restoration of RAR beta 2 into RAR beta-negative lung cancer cell lines has been reported to inhibit tumorigenicity. Since RAR beta 2 inactivation may contribute to lung cancer, we have investigated the molecular mechanism of defective RAR beta 2 expression. Nuclear run-on assays and transient transfections with RAR beta 2 promoter constructs indicate the presence of trans-acting transcriptional defects in most lung cancer cell lines, which map to the RA response element (RARE). These defects cannot be complemented by RAR-retinoid X receptor cotransfection and can be separated into two types: (i) one affecting transcription from direct repeat RAREs, but not palindromic RAREs, and (ii) another affecting transcription from both types of RARE. Studies using chimeras between RAR alpha, TR alpha, and other transcription factors suggest the existence of novel RAR-thyroid hormone receptor AF-2-specific cofactors, which are necessary for high levels of transcription. Furthermore, these factors may be frequently inactivated in human lung cancer. PMID:7791800

  8. Loss of AF6/afadin, a marker of poor outcome in breast cancer, induces cell migration, invasiveness and tumor growth.

    PubMed

    Fournier, G; Cabaud, O; Josselin, E; Chaix, A; Adélaïde, J; Isnardon, D; Restouin, A; Castellano, R; Dubreuil, P; Chaffanet, M; Birnbaum, D; Lopez, M

    2011-09-01

    Afadin/AF6, an F-actin-binding protein, is ubiquitously expressed in epithelia and has a key role during development, through its regulatory role in cell-cell junction organization. Afadin loss of expression in 15% of breast carcinoma is associated with adverse prognosis and increased risk of metastatic relapse. To determine the role of afadin in breast cancer, we studied the functional consequences of afadin protein extinction using in vitro and in vivo models. Three different breast cancer cell lines representative of the major molecular subtypes were stably repressed for afadin expression (knockdown of afadin (afadin KD)) using RNA interference. Collective and individual migrations as well as Matrigel invasion were markedly increased in afadin KD cells. Heregulin-β1 (HRG-β1)-induced migration and invasion were increased by twofold in afadin KD cells. Conversely, ectopic expression of afadin in the afadin-negative T47D cell line inhibited spontaneous and HRG-β1-induced migrations. RAS/MAPK and SRC kinase pathways were activated in afadin KD cells. Activation levels positively correlated with migration and invasion strength. Use of MEK1/2 (U0126) and SRC kinases (SU6656) inhibitors reduced afadin-dependent migration and invasion. Afadin extinction in the SK-BR-3 cell line markedly accelerated tumor growth development in mouse mammary gland and lung metastasis formation. These results may explain why the loss of afadin expression in tumors correlates with high tumor size and poor metastasis-free survival in patients. PMID:21478912

  9. [Thomas Ionescu versus Wildhem von Waldeyer. Rectum sheath or fascia propria recti? The story of a wandering idea].

    PubMed

    Vasilescu, C

    2010-01-01

    Anatomical knowledge of rectum and its fascial relationship is crucial in modem surgery and it represents the basis of total mesorectal excision. Most of the contemporary authors make reference to Waldeyer's description and use the name fascia propria recti. However, there are evidence regarding Thomas Jonnesco's priority in describing this fascial structure 5 years before Waldeyer. Thomas Jonnesco's description was published in a famous anatomy textbook: Traité d'Anatomie Humaine, Paris, Bataille, 1894, editor P. Poirier, where Thomas Jonnesco was the author of volume 4, fascicule 1, containing the anatomy of the digestive system. His description of the rectum sheath precedes Waldeyer's publication (Das Becken, Cohen, Bonn, 1899). The description of the rectum sheath is included also into the second edition of Traité d'Anatomie Humaine (editors P. Poirier and A. Charpy) published again in 1901 at Masson Publishing House. This second version, better known by contemporary authors (Chapuis et al. Dis Colon Rectum 2002;45:1), probably revised by Charpy, is no more so simple and so clear as the first one. In our paper Thomas Jonnesco's original description of rectal fascia (rectum sheath), published in 1894, is facsimiled, the two succesive editions of the book are compared and a comparison with Waldeyer's description of fascia propria recti is done. The priority of Thomas Jonnesco seems to be well proved. In this respect our own research is in line with the observations of Chapuis and Bell si colab. PMID:20726295

  10. Expression of E1AF/PEA3, an Ets-related transcription factor in human non-small-cell lung cancers: its relevance in cell motility and invasion.

    PubMed

    Hiroumi, H; Dosaka-Akita, H; Yoshida, K; Shindoh, M; Ohbuchi, T; Fujinaga, K; Nishimura, M

    2001-09-01

    Cell invasion and metastasis characterize the malignant potential of non-small-cell lung cancers (NSCLCs). We have previously reported that E1AF, a member of the Ets-related transcription factor family, confers invasive phenotype on breast cancer and oral squamous-cell carcinoma cell lines. In our study, we analyzed the E1AF expression in cell lines and resected tumors of NSCLCs by Northern blot and in situ hybridization analyses and found that 15 of 17 cell lines and 12 of 19 tumors expressed E1AF mRNA while normal lung tissue and concomitant normal cells within tumors did not. To examine the biologic importance of E1AF in NSCLCs, we introduced the E1AF gene into VMRC-LCD and NCI-H226, NSCLC cell lines lacking E1AF expression, and examined cell motility and invasion activities. E1AF-transfected VMRC-LCD cells showed increased cell motility that was 2-fold that of parental and vector-transfected control cells (p < 0.01), and both cell motility and invasion were increased 1.6-fold in NCI-H226 (p < 0.01). Furthermore, hepatocyte growth factor (HGF), which is one of the most effective cell-scattering factors, stimulated the motile and invasive activities in E1AF-transfected VMRC-LCD and NCI-H226 cells but not in their parental or vector-transfected control cells. Ets-1 mRNA expression was found in E1AF-transfected VMRC-LCD cells but not in parental or vector-transfected cells. HGF further induced expression of the Ets-1 and urokinase-type plasminogen activator (uPA) genes specifically in E1AF-transfected cells. These findings suggest that E1AF plays a substantial role in the cell motility and invasion of NSCLCs. PMID:11519038

  11. Diastasis recti abdominis during pregnancy and 12 months after childbirth: prevalence, risk factors and report of lumbopelvic pain

    PubMed Central

    Tennfjord, Merete Kolberg; Hilde, Gunvor; Ellström-Engh, Marie; Bø, Kari

    2016-01-01

    Background/aim Diastasis recti abdominis (DRA) is defined as a separation of the 2 muscle bellies of rectus abdominis. To date there is scant knowledge on prevalence, risk factors, and consequences of the condition. The present study aimed to investigate the prevalence of DRA during pregnancy and post partum, presence of possible risk factors, and the occurrence of lumbopelvic pain among women with and without DRA. Methods This prospective cohort study followed 300 first-time pregnant women from pregnancy till 12 months post partum. Data were collected by electronic questionnaire and clinical examinations. DRA was defined as a palpated separation of ≥2 fingerbreadths either 4.5 cm above, at or 4.5 cm below the umbilicus. Women with and without DRA were compared with independent samples Student's t-test and χ2/Fisher exact test, and OR with significance level >0.05. Results Prevalence of DRA was 33.1%, 60.0%, 45.4%, and 32.6% at gestation week 21, 6 weeks, 6 months and 12 months post partum, respectively. No difference in risk factors was found when comparing women with and without DRA. OR showed a greater likelihood for DRA among women reporting heavy lifting ≥20 times weekly (OR 2.18 95% CI 1.05 to 4.52). There was no difference in reported lumbopelvic pain (p=0.10) in women with and without DRA. Conclusions Prevalence of mild DRA was high both during pregnancy and after childbirth. Women with and without DRA reported the same amount of lumbopelvic pain 12 months post partum. PMID:27324871

  12. Bisphenol AF-induced endogenous transcription is mediated by ERα and ERK1/2 activation in human breast cancer cells.

    PubMed

    Li, Ming; Guo, Jing; Gao, Wenhui; Yu, Jianlong; Han, Xiaoyu; Zhang, Jing; Shao, Bing

    2014-01-01

    Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERα and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERα-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERα-positive T47D and MCF7 cells as well as overexpression of ERα in ERα-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ERα and ERK1/2 activation in human breast cancer cells. PMID:24727858

  13. Bisphenol AF-Induced Endogenous Transcription Is Mediated by ERα and ERK1/2 Activation in Human Breast Cancer Cells

    PubMed Central

    Li, Ming; Guo, Jing; Gao, Wenhui; Yu, Jianlong; Han, Xiaoyu; Zhang, Jing; Shao, Bing

    2014-01-01

    Bisphenol AF (BPAF)-induced transcriptional activity has been evaluated by luciferase reporter assay. However, the molecular mechanism of BPAF-induced endogenous transcription in human breast cancer cells has not been fully elucidated. In the present study, we investigated the effect and mechanism of BPAF-induced endogenous transcription detected by real-time PCR in human breast cancer cells. We found that BPAF stimulated transcription of estrogen responsive genes, such as trefoil factor 1 (TFF1), growth regulation by estrogen in breast cancer 1 (GREB1) and cathepsin D (CTSD), through dose-dependent and time-dependent manners in T47D and MCF7 cells. Gene-silencing of ERα, ERβ and G protein-coupled estrogen receptor 1 (GPER) by small interfering RNA revealed that BPAF-induced endogenous transcription was dependent on ERα and GPER, implying both genomic and nongenomic pathways might be involved in the endogenous transcription induced by BPAF. ERα-mediated gene transcription was further confirmed by inhibition of ER activity using ICI 182780 in ERα-positive T47D and MCF7 cells as well as overexpression of ERα in ERα-negative MDA-MB-231 breast cancer cells. Moreover, we utilized Src tyrosine kinase inhibitor PP2 and two MEK inhibitors PD98059 and U0126 to elucidate the rapid nongenomic activation of Src/MEK/ERK1/2 cascade on endogenous transcription. Our data showed that BPAF-induced transcription could be significantly blocked by PP2, PD98059 and U0126, suggesting activation of ERK1/2 was also required to regulate endogenous transcription. Taken together, these results indicate that BPAF-induced endogenous transcription of estrogen responsive genes is mediated through both genomic and nongenomic pathways involving the ERα and ERK1/2 activation in human breast cancer cells. PMID:24727858

  14. Bisphenol AF stimulates transcription and secretion of C-X-C chemokine ligand 12 to promote proliferation of cultured T47D breast cancer cells.

    PubMed

    Li, Ming; Han, Xiaoyu; Gao, Wenhui; Chen, Feng; Shao, Bing

    2015-12-01

    Bisphenol AF (4,4'-hexafluoroisopropylidene-2-diphenol, BPAF), an endocrine disruptor, has been shown to stimulate the proliferation of human breast cancer cells. However, the underlying mechanism has not been fully elucidated. We found that BPAF promoted the in vitro proliferation of estrogen receptor α (ERα)-positive breast cancer cells (T47D and MCF7), but not ERα-negative cells (MDA-MB-231 and MDA-MB-435s). BPAF significantly stimulated the proliferation of cultured T47D cell in a dose-dependent manner, and the half-maximal effective concentration (EC50) was approximately 123 nM. We employed lentivirus-mediated short hairpin RNA (shRNA) to knockdown ERα and ER antagonist ICI 182780 to inhibit ER activation, which resulted in the repression of BPAF-induced proliferation of T47D and MCF7 cells. We observed that C-X-C chemokine ligand 12 (CXCL12) was up-regulated in T47D cells under treatment with BPAF. Quantitative real-time PCR results showed that BPAF caused a time and dose dependent increase in mRNA level of CXCL12. Furthermore, treatment of T47D cells with BPAF increased CXCL12 secretion according to ELISA assay. BPAF-induced CXCL12 transcription and secretion was significantly attenuated by small interfering RNA (siRNA) targeting ERα and ICI 182780, indicating BPAF-induced CXCL12 expression is mediated through ERα. Notably, knockdown CXCL12 in T47D cells significantly attenuated BPAF-induced cell proliferation. We also observed that inhibition of CXCL12 binding to its receptors CXCR4 and CXCR7 by chalcone 4 blocked BPAF-induced cell growth. Our results indicated that CXCL12 facilitated BPAF-induced proliferation of T47D cells. Taken together, our data provided support that BPAF stimulated transcription and secretion of CXCL12 depending on ERα, and ERα/CXCL12 signaling positively regulated BPAF-induced proliferation of cultured T47D breast cancer cells. PMID:26435001

  15. Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study)

    PubMed Central

    Takeuchi, K.; Togashi, Y.; Kamihara, Y.; Fukuyama, T.; Yoshioka, H.; Inoue, A.; Katsuki, H.; Kiura, K.; Nakagawa, K.; Seto, T.; Maemondo, M.; Hida, T.; Harada, M.; Ohe, Y.; Nogami, N.; Yamamoto, N.; Nishio, M.; Tamura, T.

    2016-01-01

    Background Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. Patients and methods In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. Result ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Conclusions Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. Registration number JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center). PMID:26487585

  16. Prevention of Obesity and Insulin Resistance by Estrogens Requires ERα Activation Function-2 (ERαAF-2), Whereas ERαAF-1 Is Dispensable

    PubMed Central

    Handgraaf, Sandra; Riant, Elodie; Fabre, Aurélie; Waget, Aurélie; Burcelin, Rémy; Lière, Philippe; Krust, Andrée; Chambon, Pierre; Arnal, Jean-François; Gourdy, Pierre

    2013-01-01

    The beneficial metabolic actions of estrogen-based therapies are mainly mediated by estrogen receptor α (ERα), a nuclear receptor that regulates gene transcription through two activation functions (AFs): AF-1 and AF-2. Using mouse models deleted electively for ERαAF-1 (ERαAF-1°) or ERαAF-2 (ERαAF-2°), we determined their respective roles in the actions of estrogens on body composition and glucose homeostasis in response to either a normal diet or a high-fat diet (HFD). ERαAF-2° males and females developed accelerated weight gain, massive adiposity, severe insulin resistance, and glucose intolerance—quite reminiscent of the phenotype observed in mice deleted for the entire ERα protein (ERα−/−). In striking contrast, ERαAF-1° and wild-type (wt) mice shared a similar metabolic phenotype. Accordingly, 17β-estradiol administration regulated key metabolic genes in insulin-sensitive tissues and conferred a strong protection against HFD-induced metabolic disturbances in wt and ERαAF-1° ovariectomized mice, whereas these actions were totally abrogated in ERαAF-2° and ERα−/− mice. Thus, whereas both AFs have been previously shown to contribute to endometrial and breast cancer cell proliferation, the protective effect of estrogens against obesity and insulin resistance depends on ERαAF-2 but not ERαAF-1, thereby delineating new options for selective modulation of ERα. PMID:23903353

  17. AFS controlling algorithm

    NASA Astrophysics Data System (ADS)

    Liu, Hong; Jiang, Lanfang; Wang, Gengjie; Wang, Li

    2008-12-01

    Adaptive front lighting system (i.e., AFS) is the development trend of lighting system of motor vehicles. AFS means that headlamp can adjust beam direction to get best illumination according to road condition and its bodywork. The paper discusses the AFS key techniques: establishing calculation formulae of vehicle body state concerned road condition and steering state. Because of sensor technology limitations, it only can deal with inclination and turn of vehicle body state by means of sensor's signals. This paper studies the relationship between inclination and turn of the body and lamp lighting on the base of relative standards, and gives out the calculation formulae for the body and lamp lighting adjustment, also discusses its dynamical properties. The study is basic work for lighting adjustment automatically.

  18. [Reducing the side effects of aggressive chemotherapy (cisplatin and epirubicin) with xenogenic peptides (factor AF2) in patients with hormone refractory metastatic prostate cancer. A prospective, randomized study].

    PubMed

    Papadopoulos, I; Wand, H

    1989-06-01

    The indication of a chemotherapy is advisable with patients who are suffering from a progressively metastasised, secondarily hormone refractory carcinoma of the prostate. In search of efficient chemotherapy protocols we combined cisplatin with epirubicin (PE scheme) in our clinic. Massive side effects of that aggressive chemotherapy scheme like gastro-intestinal trouble and myelotoxicity are the limiting factors of the scheme. With measures like reducing the dosage, delaying the next cycle, or breaking off the therapy the effective dosage can often not be achieved. The anti-emetics which are usually used today exclusively give anti-emetic protection. The additional administration of xenogenic peptides (Factor AF2) had additionally myeloprotective effect in former studies. In this study we examined whether, by additionally giving Factor AF2, the patients' subjective condition, and above all their hemogram, could be stabilised in order to achieve the effective dosage or dosage intensity. For that, the patients were prospectively randomised in two groups by means of a random selection board. The analysis of the data gained in the protocol showed that the additional administration of Factor AF2 improves the patients' subjective conditions significantly. Apart from that, we noticed a considerable reduction of the vomiting frequency. Concerning the objective measured parameters of the leukocytes, thrombocytes, erythrocytes, and the hemoglobin level, the significantly myeloprotective effect of Factor AF2 could be proved. Due to the fact that in the verum group there were considerably fewer cases of breaking off or delays of the treatment than in the control group, the effective dosage intensity could be achieved with a higher number of patients in that group. PMID:2691943

  19. Prevalence and risk factors of diastasis recti abdominis from late pregnancy to 6 months postpartum, and relationship with lumbo-pelvic pain.

    PubMed

    Fernandes da Mota, Patrícia Gonçalves; Pascoal, Augusto Gil Brites Andrade; Carita, Ana Isabel Andrade Dinis; Bø, Kari

    2015-02-01

    Diastasis recti abdominis (DRA) is an impairment characterized by a midline separation of the rectus abdominis muscles along the linea alba. It has its onset during pregnancy and the first weeks following childbirth. There is scant knowledge on both prevalence and risk factors for development of the condition. The aim of this study was to investigate the prevalence of DRA at gestational week 35 and three timepoints postpartum, possible risk factors, and the relationship between DRA and lumbo-pelvic pain. Ultrasound images of inter rectus distance (IRD) were recorded in 84 healthy primiparous women, at three locations on the linea alba. The IRD was measured at: gestational week 35 and 6-8, 12-14, and 24-26 weeks postpartum. Diagnosis of DRA was defined as 16 mm at 2 cm below the umbilicus. Independent sample t-test and binary logistic regression was used to assess differences and risk factors in women with and without DRA and women with and without lumbo-pelvic pain. P < 0.05 was considered statistically significant. The prevalence of DRA decreased from 100% at gestational week 35-39% at 6 months postpartum. No statistically significant differences were found in prepregnancy body mass index (BMI), weight gain, baby's birth weight or abdominal circumference between women with and without DRA at 6 months postpartum. Women with DRA at 6 months postpartum were not more likely to report lumbo-pelvic pain than women without DRA. DRA is prevalent at 6 months postpartum, but is not linked with lumbo-pelvic pain. PMID:25282439

  20. Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer.

    PubMed

    Letessier, A; Garrido-Urbani, S; Ginestier, C; Fournier, G; Esterni, B; Monville, F; Adélaïde, J; Geneix, J; Xerri, L; Dubreuil, P; Viens, P; Charafe-Jauffret, E; Jacquemier, J; Birnbaum, D; Lopez, M; Chaffanet, M

    2007-01-11

    Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors. PMID:16819513

  1. Pathophysiology of cancer therapy-provoked atrial fibrillation.

    PubMed

    Cheng, Wan-Li; Kao, Yu-Hsun; Chen, Shih-Ann; Chen, Yi-Jen

    2016-09-15

    Atrial fibrillation (AF) occurs with increased frequency in cancer patients, especially in patients who undergo surgery or chemotherapy. AF disturbs the prognosis of cancer patients and challenges therapeutic outcomes of cancer treatment. Elucidating the mechanisms of cancer-induced AF would help identify specific strategies for preventing AF occurrence. In addition to concurrent risk factors of cancer and AF, cancer surgery, side effects of anticancer agents, and cancer-associated immune responses play critical roles in the genesis of AF. In this review, we provide succinct potential mechanisms of AF genesis in cancer patients. PMID:27327505

  2. Genomic functions of U2AF in constitutive and regulated splicing

    PubMed Central

    Wu, Tongbin; Fu, Xiang-Dong

    2015-01-01

    The U2AF heterodimer is generally accepted to play a vital role in defining functional 3′ splice sites in pre-mRNA splicing. Given prevalent mutations in U2AF, particularly in the U2AF1 gene (which encodes for the U2AF35 subunit) in blood disorders and other human cancers, there are renewed interests in these classic splicing factors to further understand their regulatory functions in RNA metabolism in both physiological and disease settings. We recently reported that U2AF has a maximal capacity to directly bind ˜88% of functional 3′ splice sites in the human genome and that numerous U2AF binding events also occur in various exonic and intronic locations, thus providing additional mechanisms for the regulation of alternative splicing besides their traditional role in titrating weak splice sites in the cell. These findings, coupled with the existence of multiple related proteins to both U2AF65 and U2AF35, beg a series of questions on the universal role of U2AF in functional 3′ splice site definition, their binding specificities in vivo, potential mechanisms to bypass their requirement for certain intron removal events, contribution of splicing-independent functions of U2AF to important cellular functions, and the mechanism for U2AF mutations to invoke specific diseases in humans. PMID:25901584

  3. Atrial Fibrillation (AF or AFib)

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Atrial Fibrillation (AF or AFib) Updated:Feb 10,2016 What ... to the Terms and Conditions and Privacy Policy Atrial Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • ...

  4. Pathogenesis of AF: Impact on intracardiac signals

    PubMed Central

    Shah, Ashok J; Dubois, Rémi; Miyazaki, Shinsuke; Jadidi, Amir S; Scherr, Daniel; Wilton, Stephen B; Roten, Laurent; Pascale, Patrizio; Pedersen, Michala; Derval, Nicolas; Knecht, Sebastien; Sacher, Frederic; Jais, Pierre; Narayan, Sanjiv; Hocini, Mélèze; Haïssaguerre, Michel

    2014-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is responsible for the highest number of rhythm-related disorders and cardioembolic strokes worldwide. Intracardiac signal analysis during the onset of paroxysmal AF led to the discovery of pulmonary vein as a triggering source of AF, which has led to the development of pulmonary vein ablation—an established curative therapy for drug-resistant AF. Complex, multicomponent and rapid electrical activity widely involving the atrial substrate characterizes persistent/permanent AF. Widespread nature of the problem and complexity of signals in persistent AF reduce the success rate of ablation therapy. Although signal processing applied to extraction of relevant features from these complex electrograms has helped to improve the efficacy of ablation therapy in persistent/permanent AF, improved understanding of complex signals should help to identify sources of AF and further increase the success rate of ablation therapy. PMID:22255589

  5. Study about AFS swerve mode

    NASA Astrophysics Data System (ADS)

    Liu, Hong; Jiang, Lanfang; Zhao, Qin; Wang, Li

    2009-11-01

    A swerving mathematical model was established after stating the shortage of the present AFS swerving algorithm. The conception of 'expected lighting distance' was extended to 'expected lighting bound' and approximate treatment of geometry of light beam falling to ground of headlamp was processed. The expected lighting bound was ascertained and the lighting range of turning angle of headlamp was calculated. The calculation formula of turning angle of headlamp was worked out. It was indicated that the turning angle of inside and outside of headlamp calculated by revised algorithm was reasonable by comparing calculation. Finally the control strategy about the turning angle of inside and outside headlamp when turning was worked out. It is of practical significance in promoting the active safety, reducing the traffic accidents caused by insufficient angle and range of irradiation of headlamp.

  6. Eaton AF5000+Genesis Communication Driver

    Energy Science and Technology Software Center (ESTSC)

    1995-05-25

    Communication driver allows the Genesis Control Series software to interact with Eaton AF5000+ frequency drives via RS-232 communications. All Eaton AF5000+ parameters that support communications are supported by the Genesis driver. Multidrop addressing to multiple units is available with the Genesis communication driver.

  7. STBC AF relay for unmanned aircraft system

    NASA Astrophysics Data System (ADS)

    Adachi, Fumiyuki; Miyazaki, Hiroyuki; Endo, Chikara

    2015-01-01

    If a large scale disaster similar to the Great East Japan Earthquake 2011 happens, some areas may be isolated from the communications network. Recently, unmanned aircraft system (UAS) based wireless relay communication has been attracting much attention since it is able to quickly re-establish the connection between isolated areas and the network. However, the channel between ground station (GS) and unmanned aircraft (UA) is unreliable due to UA's swing motion and as consequence, the relay communication quality degrades. In this paper, we introduce space-time block coded (STBC) amplify-and-forward (AF) relay for UAS based wireless relay communication to improve relay communication quality. A group of UAs forms single frequency network (SFN) to perform STBC-AF cooperative relay. In STBC-AF relay, only conjugate operation, block exchange and amplifying are required at UAs. Therefore, STBC-AF relay improves the relay communication quality while alleviating the complexity problem at UAs. It is shown by computer simulation that STBC-AF relay can achieve better throughput performance than conventional AF relay.

  8. [Evaluation of the complementary drug Factor AF2 as a supportive agent in management of advanced urothelial carcinoma. Prospective randomized multicenter study].

    PubMed

    Krege, S; Hinke, A; Otto, T; Rübben, H

    2002-03-01

    This is a prospective randomized multicenter trial for evaluation of the biological response modifier Factor AF2 in advanced urothelial cancer treated with chemotherapy. Main aim of the study was the analysis of supportive effects. Additionally patients were examined with regard to tumor response, time to progression and survival. 106 patients with advanced urothelial cancer received chemotherapy with cisplatin and methotrexate. They were randomized for additional Factor AF2 (500 mg i.v., given at days 0-3, 7-10 and 11-14). Myelotoxicity was more common and severe in the group without Factor AF2 reaching statistical significance. Gastrointestinal side effects occurred in both groups, though grade III to IV toxicity was more common without Factor AF2. Overall remission rate was 38%, median survival 33 weeks, mean time to progression 20 weeks. There was no significant difference between the two groups with or without Factor AF2. PMID:11993095

  9. Cancer

    MedlinePlus

    ... Leukemia Liver cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer ... have any symptoms. In certain cancers, such as pancreatic cancer, symptoms often do not start until the disease ...

  10. Korean Atrial Fibrillation (AF) Network: Genetic Variants for AF Do Not Predict Ablation Success

    PubMed Central

    Choi, Eue-Keun; Park, Jae Hyung; Lee, Ji-Young; Nam, Chung Mo; Hwang, Min Ki; Uhm, Jae-Sun; Joung, Boyoung; Ko, Young-Guk; Lee, Moon-Hyoung; Lubitz, Steven A; Ellinor, Patrick T; Pak, Hui-Nam

    2015-01-01

    Background Genomewide association studies have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between top susceptibility loci and AF recurrence after ablation have not been examined in Asian populations. We examined whether the top single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (PITX2), 16q22 (ZFHX3), and 1q21 (KCNN3) were associated with AF in a Korean population and whether these SNPs were associated with clinical outcomes after catheter ablation for AF. Methods and Results We determined the association between 4 SNPs and AF in 1068 AF patients who underwent catheter ablation (74.6% male, aged 57.5±10.9 years, 67.9% paroxysmal AF) and 1068 age- and sex-matched controls. The SNPs at the PITX2 and ZFHX3 loci, but not the KCNN3 locus, were significantly associated with AF (PITX2/rs6843082_G: odds ratio 3.41, 95% CI 2.55 to 4.55, P=1.32×10−16; PITX2/rs2200733_T: odds ratio 2.05, 95% CI 1.66 to 2.53, P=2.20×10−11; ZFHX3/rs2106261_A: odds ratio 2.33, 95% CI 1.87 to 2.91, P=3.75×10−14; KCNN3/rs13376333_T: odds ratio 1.74, 95% CI 0.93 to 3.25, P=0.085). Among those patients who underwent catheter ablation for AF, none of the top AF-associated SNPs were associated with long-term clinical recurrence of AF after catheter ablation. Conclusions SNPs at the PITX2 and ZFHX3 loci were strongly associated with AF in Korean patients. In contrast to prior reports, none of the 4 top AF-susceptibility SNPs predicted clinical recurrence after catheter ablation. PMID:26272656

  11. Degradation of AF1Q by chaperone-mediated autophagy

    SciTech Connect

    Li, Peng; Ji, Min; Lu, Fei; Zhang, Jingru; Li, Huanjie; Cui, Taixing; Li Wang, Xing; Tang, Dongqi; Ji, Chunyan

    2014-09-10

    AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA. - Highlights: • Chaperone-mediated autophagy (CMA) is involved in the degradation of AF1Q. • Macroautophagy does not contribute to the AF1Q degradation. • AF1Q has a KFERQ-like motif that is recognized by CMA core components.

  12. AFS Estuaries Section - A Successful Partnership

    EPA Science Inventory

    The Estuaries Section of the American Fisheries Society offers travel awards to students in support of their attendance and presentations at the AFS meeting. Since 2007, the Southern Association of Marine Laboratories has partnered with the Estuaries Section to sponsor two stude...

  13. Health Information in Somali (af Soomaali): MedlinePlus

    MedlinePlus

    ... af Soomaali (Somali) Bilingual PDF Health Information Translations Animal Bites Animal Bites and Scratches Qaniinyada iyo Xagashada Xayawaanka - af ... Soomaali (Somali) Bilingual PDF Health Information Translations Radiation Therapy Preventing Infections When Your White Blood Cell Count ...

  14. Health Information in Somali (af Soomaali): MedlinePlus

    MedlinePlus

    ... Bilingual PDF Health Information Translations Appendectomy for a Child Qabsin-saarid ilmo - af Soomaali (Somali) Bilingual PDF ... Somali) Bilingual PDF Health Information Translations Asthma in Children Nebulizer Treatments Daawenta wal in Xaqiiqsanaan - af Soomaali ( ...

  15. Lessons from the dissection of the activation functions (AF-1 and AF-2) of the estrogen receptor alpha in vivo.

    PubMed

    Arnal, Jean-François; Fontaine, Coralie; Abot, Anne; Valera, Marie-Cécile; Laurell, Henrik; Gourdy, Pierre; Lenfant, Françoise

    2013-06-01

    Estrogens influence most of the physiological processes in mammals, including but not limited to reproduction, cognition, behavior, vascular system, metabolism and bone integrity. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen influence the pathophysiology of numerous diseases, including cancer (of the reproductive tract as breast, endometrial but also colorectal, prostate,…), as well as neurodegenerative, inflammatory-immune, cardiovascular and metabolic diseases, and osteoporosis. These actions are mediated by the activation of estrogen receptors (ER) alpha (ERα) and beta (ERβ), which regulate target gene transcription (genomic action) through two independent activation functions (AF)-1 and AF-2, but can also elicit rapid membrane initiated steroid signals (MISS). Targeted ER gene inactivation has shown that although ERβ plays an important role in the central nervous system and in the heart, ERα appears to play a prominent role in most of the other tissues. Pharmacological activation or inhibition of ERα and/or ERβ provides already the basis for many therapeutic interventions, from hormone replacement at menopause to prevention of the recurrence of breast cancer. However, the use of these estrogens or selective estrogen receptors modulators (SERMs) have also induced undesired effects. Thus, an important challenge consists now to uncouple the beneficial actions from other deleterious ones. The in vivo molecular "dissection" of ERα represents both a molecular and integrated approach that already allowed to delineate in mouse the role of the main "subfunctions" of the receptor and that could pave the way to an optimization of the ER modulation. PMID:23200732

  16. Microfluidic Pumps Containing Teflon [Trademark] AF Diaphragms

    NASA Technical Reports Server (NTRS)

    Willis, Peter; White, Victor; Grunthaner, Frank; Ikeda, Mike; Mathies, Richard A.

    2009-01-01

    Microfluidic pumps and valves based on pneumatically actuated diaphragms made of Teflon AF polymers are being developed for incorporation into laboratory-on-a-chip devices that must perform well over temperature ranges wider than those of prior diaphragm-based microfluidic pumps and valves. Other potential applications include implanted biomedical microfluidic devices, wherein the biocompatability of Teflon AF polymers would be highly advantageous. These pumps and valves have been demonstrated to function stably after cycling through temperatures from -125 to 120 C. These pumps and valves are intended to be successors to similar prior pumps and valves containing diaphragms made of polydimethylsiloxane (PDMS) [commonly known as silicone rubber]. The PDMS-containing valves ae designed to function stably only within the temperature range from 5 to 80 C. Undesirably, PDMS membranes are somwehat porous and retain water. PDMS is especially unsuitable for use at temperatures below 0 C because the formation of ice crystals increases porosity and introduces microshear.

  17. An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model

    PubMed Central

    Bergerson, Rachel J.; Collier, Lara S.; Sarver, Aaron L.; Been, Raha A.; Lugthart, Sanne; Diers, Miechaleen D.; Zuber, Johannes; Rappaport, Amy R.; Nixon, Molly J.; Silverstein, Kevin A. T.; Fan, Danhua; Lamblin, Anne-Francoise J.; Wolff, Linda; Kersey, John H.; Delwel, Ruud; Lowe, Scott W.; O'Sullivan, M. Gerard; Kogan, Scott C.; Adams, David J.

    2012-01-01

    Patients with a t(9;11) translocation (MLL-AF9) develop acute myeloid leukemia (AML), and while in mice the expression of this fusion oncogene also results in the development of myeloid leukemia, it is with long latency. To identify mutations that cooperate with Mll-AF9, we infected neonatal wild-type (WT) or Mll-AF9 mice with a murine leukemia virus (MuLV). MuLV-infected Mll-AF9 mice succumbed to disease significantly faster than controls presenting predominantly with myeloid leukemia while infected WT animals developed predominantly lymphoid leukemia. We identified 88 candidate cancer genes near common sites of proviral insertion. Analysis of transcript levels revealed significantly elevated expression of Mn1, and a trend toward increased expression of Bcl11a and Fosb in Mll-AF9 murine leukemia samples with proviral insertions proximal to these genes. Accordingly, FOSB and BCL11A were also overexpressed in human AML harboring MLL gene translocations. FOSB was revealed to be essential for growth in mouse and human myeloid leukemia cells using shRNA lentiviral vectors in vitro. Importantly, MN1 cooperated with Mll-AF9 in leukemogenesis in an in vivo BM viral transduction and transplantation assay. Together, our data identified genes that define transcription factor networks and important genetic pathways acting during progression of leukemia induced by MLL fusion oncogenes. PMID:22427200

  18. Context, Context, Context: New Gene Programs Linked to Bad Behavior in MLL-AF9-Initiated Leukemia.

    PubMed

    Watanabe, Tatsuro; Ernst, Patricia

    2016-07-11

    In this issue of Cancer Cell, Stavropoulou et al. report that expression of the MLL-AF9 fusion results in acute myelogenous leukemia (AML) with different behaviors depending on cell context, which leads them to identify a transcriptional signature surprisingly resembling that of the epithelial-to-mesenchymal (EMT) transition, correlating with aggressiveness of disease. PMID:27411579

  19. Cancer

    MedlinePlus

    ... body. Cancerous cells are also called malignant cells. Causes Cancer grows out of cells in the body. Normal ... of many cancers remains unknown. The most common cause of cancer-related death is lung cancer. In the U.S., ...

  20. 4:2:1 conduction of an AF initiating trigger

    PubMed Central

    Kojodjojo, Pipin; Chong, Eric; Lim, Toon Wei; Seow, Swee Chong

    2015-01-01

    A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus. PMID:27134438

  1. AF4 and AF4N protein complexes: recruitment of P-TEFb kinase, their interactome and potential functions

    PubMed Central

    Scholz, Bastian; Kowarz, Eric; Rössler, Tanja; Ahmad, Khalil; Steinhilber, Dieter; Marschalek, Rolf

    2015-01-01

    AF4/AFF1 and AF5/AFF4 are the molecular backbone to assemble “super-elongation complexes” (SECs) that have two main functions: (1) control of transcriptional elongation by recruiting the positive transcription elongation factor b (P-TEFb = CyclinT1/CDK9) that is usually stored in inhibitory 7SK RNPs; (2) binding of different histone methyltransferases, like DOT1L, NSD1 and CARM1. This way, transcribed genes obtain specific histone signatures (e.g. H3K79me2/3, H3K36me2) to generate a transcriptional memory system. Here we addressed several questions: how is P-TEFb recruited into SEC, how is the AF4 interactome composed, and what is the function of the naturally occuring AF4N protein variant which exhibits only the first 360 amino acids of the AF4 full-length protein. Noteworthy, shorter protein variants are a specific feature of all AFF protein family members. Here, we demonstrate that full-length AF4 and AF4N are both catalyzing the transition of P-TEFb from 7SK RNP to their N-terminal domain. We have also mapped the protein-protein interaction network within both complexes. In addition, we have first evidence that the AF4N protein also recruits TFIIH and the tumor suppressor MEN1. This indicate that AF4N may have additional functions in transcriptional initiation and in MEN1-dependend transcriptional processes. PMID:26171280

  2. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 14 2013-01-01 2013-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  3. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 14 2012-01-01 2012-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  4. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  5. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 14 2011-01-01 2011-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  6. 7 CFR Exhibits A-F to Subpart A... - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 14 2014-01-01 2014-01-01 false A Exhibits A-F to Subpart A of Part 1955 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS-COOPERATIVE... Real and Chattel Property Exhibits A-F to Subpart A of Part 1955...

  7. Part III: AFS - A Secure Distributed File System

    SciTech Connect

    Wachsmann, A.; /SLAC

    2005-06-29

    AFS is a secure distributed global file system providing location independence, scalability and transparent migration capabilities for data. AFS works across a multitude of Unix and non-Unix operating systems and is used at many large sites in production for many years. AFS still provides unique features that are not available with other distributed file systems even though AFS is almost 20 years old. This age might make it less appealing to some but with IBM making AFS available as open-source in 2000, new interest in use and development was sparked. When talking about AFS, people often mention other file systems as potential alternatives. Coda (http://www.coda.cs.cmu.edu/) with its disconnected mode will always be a research project and never have production quality. Intermezzo (http://www.inter-mezzo.org/) is now in the Linux kernel but not available for any other operating systems. NFSv4 (http://www.nfsv4.org/) which picked up many ideas from AFS and Coda is not mature enough yet to be used in serious production mode. This article presents the rich features of AFS and invites readers to play with it.

  8. Toward a petabyte-scale AFS service at CERN

    NASA Astrophysics Data System (ADS)

    van der Ster, Daniel; Moscicki, Jakub T.; Wiebalck, Arne

    2014-06-01

    AFS is a mature and reliable storage service at CERN, having worked for more than 20 years as the provider of Unix home directories and project areas. Recently, the AFS service has grown at unprecedented rates (200% in the past year); this growth was unlocked thanks to innovations in both the hardware and software components of our file servers. This work presents how AFS is used at CERN and how the service offering is evolving with the increasing storage needs of its local and remote user communities. In particular, we demonstrate the usage patterns for home directories, workspaces and project spaces, as well as show the daily work which is required to rebalance data and maintaining stability and performance. Finally, we highlight some recent changes and optimisations made to the AFS Service, thereby revealing how AFS can possibly operate at all while being subjected to frequent-almost DDOS-like-attacks from its users.

  9. Cancer

    MedlinePlus

    ... your life Being exposed to chemicals that can cause cancer Being at risk for skin cancer Depending on ... than nonsmokers. Other forms of tobacco can also cause cancer, such as cigars, chewing tobacco and snuff. If ...

  10. Vobatensines A-F, Cytotoxic Iboga-Vobasine Bisindoles from Tabernaemontana corymbosa.

    PubMed

    Sim, Dawn Su-Yin; Teoh, Wuen-Yew; Sim, Kae-Shin; Lim, Siew-Huah; Thomas, Noel F; Low, Yun-Yee; Kam, Toh-Seok

    2016-04-22

    Six new bisindole alkaloids of the iboga-vobasine type, vobatensines A-F (1-6), in addition to four known bisindoles (8-11), were isolated from a stem bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the spectroscopic data and in the case of vobatensines A (1), B (2), and 16'-decarbomethoxyvoacamine (8) also confirmed by partial syntheses. Nine of these alkaloids (1-5, 8-11) showed pronounced in vitro growth inhibitory activity against human KB, PC-3, LNCaP, HCT 116, HT-29, MCF7, MDA-MB-231, and A549 cancer cells. PMID:26918761

  11. An Implicit LU/AF FDTD Method

    NASA Technical Reports Server (NTRS)

    Beggs, John H.; Briley, W. Roger

    2001-01-01

    There has been some recent work to develop two and three-dimensional alternating direction implicit (ADI) FDTD schemes. These ADI schemes are based upon the original ADI concept developed by Peaceman and Rachford and Douglas and Gunn, which is a popular solution method in Computational Fluid Dynamics (CFD). These ADI schemes work well and they require solution of a tridiagonal system of equations. A new approach proposed in this paper applies a LU/AF approximate factorization technique from CFD to Maxwell s equations in flux conservative form for one space dimension. The result is a scheme that will retain its unconditional stability in three space dimensions, but does not require the solution of tridiagonal systems. The theory for this new algorithm is outlined in a one-dimensional context for clarity. An extension to two and threedimensional cases is discussed. Results of Fourier analysis are discussed for both stability and dispersion/damping properties of the algorithm. Results are presented for a one-dimensional model problem, and the explicit FDTD algorithm is chosen as a convenient reference for comparison.

  12. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)

    PubMed Central

    2012-01-01

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available. PMID:23210797

  13. Tuning the Music: Acoustic Force Spectroscopy (AFS) 2.0.

    PubMed

    Kamsma, Douwe; Creyghton, Ramon; Sitters, Gerrit; Wuite, Gijs J L; Peterman, Erwin J G

    2016-08-01

    AFS is a recently introduced high-throughput single-molecule technique that allows studying structural and mechanochemical properties of many biomolecules in parallel. To further improve the method, we developed a modelling tool to optimize the layer thicknesses, and a calibration method to experimentally validate the modelled force profiles. After optimization, we are able to apply 350pN on 4.5μm polystyrene beads, without the use of an amplifier, at the coverslip side of the AFS chip. Furthermore, we present the use of a transparent piezo to generate the acoustic force and we show that AFS can be combined with high-NA oil or water-immersion objectives. With this set of developments AFS will be applicable to a broad range of single-molecule experiments. PMID:27163865

  14. Cancer

    MedlinePlus

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  15. Effects of Iron Depletion on CALM-AF10 Leukemias

    PubMed Central

    Heath, Jessica L.; Weiss, Joshua M.

    2014-01-01

    Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis (CME). The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by CME. CALM-AF10 leukemias harbor a single copy of the normal CALM gene, and may therefore be more sensitive to the growth inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that Calm heterozygous (CalmHET) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor (sTfR) levels and reduced growth rates. CalmHET hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity towards cultured CalmHET CALM-AF10 leukemia cells and this effect was additive to that of chemotherapy. In mice transplanted with CalmHET CALM-AF10 leukemia, we found that dietary iron restriction reduces tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CalmHET CALM-AF10 leukemia. In summary, while Calm heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients. PMID:25193880

  16. [Cancer].

    PubMed

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  17. AF-GEOSpace Version 2.5: Space Environment Software

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Hall, T.; Roth, C.; Ling, A.; Ginet, G. P.; Madden, D.

    2010-12-01

    AF-GEOSpace is a graphics-intensive software program with space environment models and applications developed by the Space Weather Center of Excellence at AFRL. The software addresses a wide range of physical domains, e.g., solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. AF-GEOSpace has become a platform for developing and prototyping space weather visualization products. The new AF-GEOSpace Version 2.5 (release scheduled for 2010) expands on the content of Version 2.1 by including modules addressing the following new topics: (1) energetic proton maps for the South Atlantic Anomaly (from Ginet et al. [2007]), (2) GPS scintillation outage simulation tools, (3) magnetopause location determination (Shue et al. [1998]), (4) a plasmasphere model (Global Core Plasma Model, 2009 version based on Gallagher et al. [2000]), (5) a standard ionospheric model (International Reference Ionosphere 2007), (6) the CAMMICE/MICS model of inner magnetosphere plasma population (based on Roeder et al. [2005]), (7) magnetic field models (e.g., Tsyganenko and Sitnov [2005]), and (8) loading and displaying externally-produced 3D gridded data sets within AF-GEOSpace. Improvements to existing Version 2.1 capabilities include: (1) a 2005 update to the geomagnetic cutoff rigidity model of Smart and Shea [2003], (2) a 2005 update to the ionospheric scintillation Wide-Band Model (WBMOD) of Secan and Bussey [1994], and (3) improved magnetic field flux mapping options for the existing set of AF-GEOSpace radiation belt models. A basic review of these new AF-GEOSpace capabilities will be provided. To obtain a copy of the software, please contact the first author.

  18. AF-GEOSpace Version 2.1 Release

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Madden, D.; Perry, K. L.; Tautz, M.; Roth, C.

    2006-05-01

    AF-GEOSpace Version 2.1 is a graphics-intensive software program with space environment models and applications developed recently by the Space Weather Center of Excellence at AFRL. A review of new and planned AF-GEOSpace capabilities will be given. The software addresses a wide range of physical domains and addresses such topics as solar disturbance propagation, geomagnetic field and radiation belt configurations, auroral particle precipitation, and ionospheric scintillation. Building on the success of previous releases, AF-GEOSpace has become a platform for the rapid prototyping of automated operational and simulation space weather visualization products and helps with a variety of tasks, including: orbit specification for radiation hazard avoidance; satellite design assessment and post-event anomaly analysis; solar disturbance effects forecasting; determination of link outage regions for active ionospheric conditions; satellite magnetic conjugate studies, scientific model validation and comparison, physics research, and education. Previously, Version 2.0 provided a simplified graphical user interface, improved science and application modules, significantly enhanced graphical performance, common input data archive sets, and 1-D, 2-D, and 3- D visualization tools for all models. Dynamic capabilities permit multiple environments to be generated at user- specified time intervals while animation tools enable the display of satellite orbits and environment data together as a function of time. Building on the Version 2.0 software architecture, AF-GEOSpace Version 2.1 includes a host of new modules providing, for example, plasma sheet charged particle fluxes, neutral atmosphere densities, 3-D cosmic ray cutoff maps, low-altitude trapped proton belt flux specification, DMSP particle data displays, satellite magnetic field footprint mapping determination, and meteor sky maps and shower/storm fluxes with spacecraft impact probabilities. AF-GEOSpace Version 2.1 was

  19. GPIM AF-M315E Propulsion System

    NASA Technical Reports Server (NTRS)

    Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

    2014-01-01

    The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

  20. Induction of apoptosis in MCF-7 cells by the hemagglutinin-neuraminidase glycoprotein of Newcastle disease virus Malaysian strain AF2240.

    PubMed

    Ghrici, Mohamed; El Zowalaty, Mohamed; Omar, Abdul Rahman; Ideris, Aini

    2013-09-01

    Newcastle disease virus (NDV) exerts its naturally occurring oncolysis possibly through the induction of apoptosis. We hypothesized that the binding of the virus to the cell via the hemagglutinin-neuraminidase (HN) glycoprotein may be sufficient to not only induce apoptosis but to induce a higher apoptosis level than the parental NDV AF2240 virus. NDV AF2240 induction of apoptosis in MCF-7 human breast cancer cells was analyzed and quantified. In addition, the complete HN gene of NDV strain AF2240 was amplified, sequenced and cloned into the pDisplay eukaryotic expression vector. HN gene expression was first detected at the cell surface membrane of the transfected MCF-7 cells. HN induction of apoptosis in transfected MCF-7 cells was analyzed and quantified. The expression of the HN gene alone was able to induce apoptosis in MCF-7 cells but it was a less potent apoptosis inducer compared to the parental NDV AF2240 strain. In conclusion, the NDV AF2240 strain is a more suitable antitumor candidate agent than its recombinant HN gene unless the latter is further improved by additional modifications. PMID:23807159

  1. Molecular and functional identification of three interleukin-17A/F (IL-17A/F) homologues in large yellow croaker (Larimichthys crocea).

    PubMed

    Ding, Yang; Ao, Jingqun; Ai, Chunxiang; Chen, Xinhua

    2016-02-01

    The interleukin-17 (IL-17) cytokine family plays a central role in the coordination of inflammatory responses. In fish species, three genes that have a similar homology to both IL-17A and IL-17F were designated IL-17A/F1, 2, and 3. In this study, we identified three IL-17A/F homologues (LycIL-17A/F1, 2, and 3) from large yellow croaker (Larimichthys crocea). The deduced LycIL-17A/F1 and 3 had four cysteine residues conserved in teleost IL-17A/F1 and 3 homologues and shared a domain similar to the B chain of human IL-17F. The deduced LycIL-17A/F2 possessed the unique arrangement of six cysteine residues as teleost IL-17A/F2 (except Fugu IL-17A/F2) and higher vertebrate IL-17A and F, and shared a domain similar to the D/E chain of human IL-17A. Phylogenetic analysis showed that teleost IL-17A/F1 and 3 fall into a major clade, whereas IL-17A/F2 forms a separated clade and is clustered with IL-17N. Based on structural and phylogenetic analyses, we suggest that teleost IL-17A/Fs may be classified into two subgroups: one consisting of IL-17A/F1 and 3, and the other composed of IL-17A/F2. The three LycIL-17A/Fs were constitutively expressed in all tissues examined although at a different level. Following challenge with Aeromonas hydrophila, expression of these three LycIL-17A/Fs was rapidly increased in head kidney and gills. The in vivo assays showed that recombinant LycIL-17A/F1, 2, and 3 all were able to enhance the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α2), chemokines (CXCL8 and CXCL13), and antimicrobial peptide hepcidin in head kidney. Furthermore, LycIL-17A/Fs appeared to mediate pro-inflammatory responses via NF-κB signalling. These results therefore reveal similar functions between the two subgroup members,LycIL-17A/F1 and 3 and LycIL-17A/F2, in promoting inflammation and host defences. PMID:26429410

  2. Aminoflavone-loaded EGFR-targeted unimolecular micelle nanoparticles exhibit anti-cancer effects in triple negative breast cancer.

    PubMed

    Brinkman, Ashley M; Chen, Guojun; Wang, Yidan; Hedman, Curtis J; Sherer, Nathan M; Havighurst, Thomas C; Gong, Shaoqin; Xu, Wei

    2016-09-01

    Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer for which there is no available targeted therapy. TNBC cases contribute disproportionately to breast cancer-related mortality, thus the need for novel and effective therapeutic methods is urgent. We have previously shown that a National Cancer Institute (NCI) investigational drug aminoflavone (AF) exhibits strong growth inhibitory effects in TNBC cells. However, in vivo pulmonary toxicity resulted in withdrawal or termination of several human clinical trials for AF. Herein we report the in vivo efficacy of a nanoformulation of AF that enhances the therapeutic index of AF in TNBC. We engineered a unique unimolecular micelle nanoparticle (NP) loaded with AF and conjugated with GE11, a 12 amino acid peptide targeting epidermal growth factor receptor (EGFR), since EGFR amplification is frequently observed in TNBC tumors. These unimolecular micelles possessed excellent stability and preferentially released drug payload at endosomal pH levels rather than blood pH levels. Use of the GE11 targeting peptide resulted in enhanced cellular uptake and strong growth inhibitory effects in TNBC cells. Further, AF-loaded, GE11-conjugated (targeted) unimolecular micelle NPs significantly inhibit orthotopic TNBC tumor growth in a xenograft model, compared to treatment with AF-loaded, GE11-lacking (non-targeted) unimolecular micelle NPs or free AF. Interestingly, the animals treated with AF-loaded, targeted NPs had the highest plasma and tumor level of AF among different treatment groups yet exhibited no increase in plasma aspartate aminotransferase (AST) activity level or observable tissue damage at the time of sacrifice. Together, these results highlight AF-loaded, EGFR-targeted unimolecular micelle NPs as an effective therapeutic option for EGFR-overexpressing TNBC. PMID:27267625

  3. [PREDICTING FACTORS OF THE LIFE SPAN IN PATIENTS, SUFFERING METASTATIC COLORECTAL CANCER AND SYNCHRONOUS HEPATIC AFFECTION AFTER SURGICAL TREATMENT].

    PubMed

    Kolesnik, O O; Burlaka, A A; Lukashenko, A V; Pryimak, V V; Zhukov, Yu O; Makhmudov, D E; Volk, M O; Shchepotin, I B

    2015-05-01

    The results of treatment of 125 patients, suffering metastatic hepatic affection in colorectal cancer (pT1--4N0--2M1--in colonic cancer and pT1--3N0--2M1--in cancer recti), to whom in 2008-2015 yrs a one-staged (Group 1) or two-staged (Group II) surgical treatment was done. In affection of 4 regional lymph nodes and more (pN2) late results were less favorable, than in pN1 or pN0, not depending from surgical approach choosed. In 48 (38.4%) patients with one syndromal hepatic metastatic focus, the indices of general three-year and five-year cumulative survival were the best, than in other groups--82 and 63% (p = 0.001) accordingly; in monolobar affection--68 and 49%, and in bilobar--23 and 0%, not depending from method of surgical treatment (p < 0.001) choosed. Predictive factors were established, which impact negatively the indices of general survival in patients, suffering metastatic hepatic affection in colorectal cancer: hepatic metastatic foci number 4 and more, bilobar hepatic metastatic affection. PMID:26419027

  4. An Empirical Test of Oklahoma's A-F School Grades

    ERIC Educational Resources Information Center

    Adams, Curt M.; Forsyth, Patrick B.; Ware, Jordan; Mwavita, Mwarumba; Barnes, Laura L.; Khojasteb, Jam

    2016-01-01

    Oklahoma is one of 16 states electing to use an A-F letter grade as an indicator of school quality. On the surface, letter grades are an attractive policy instrument for school improvement; they are seemingly clear, simple, and easy to interpret. Evidence, however, on the use of letter grades as an instrument to rank and improve schools is scant…

  5. R2 AIRS/AFS FACILITY GIS LAYER

    EPA Science Inventory

    The AFS subsystem contains emissions, compliance, and permit data for stationary sources regulated by the U.S. EPA and state and local air pollution agencies. This information is used by states in preparation of State Implementation Plans (SIPs), to track the compliance status ...

  6. R2 AIRS/AFS PERMITS GIS LAYER

    EPA Science Inventory

    The Region 2 AIRS/AFS Permits Regulated Facility GIS layer contains identification (name, address, ID), and location (latitude, longitude, and locational metadata), attributes of stationary source(s) of air pollution associated with facilities that are regulated by the U. S. EPA....

  7. Treatment Guidelines of Atrial Fibrillation (AFib or AF)

    MedlinePlus

    ... Pressure Tools & Resources Stroke More Treatment Guidelines of Atrial Fibrillation (AFib or AF) Updated:Jun 23,2016 What ... content was last reviewed on 04/16/14. Atrial Fibrillation • Introduction • What is Atrial Fibrillation? • Why AFib Matters • ...

  8. Extracting uranium from seawater: Promising AF series adsorbents

    SciTech Connect

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; Janke, Christopher James; Kuo, Li-Jung; Gill, Gary; Wood, Jordana; Dai, Sheng

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8 ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.

  9. Extracting uranium from seawater: Promising AF series adsorbents

    DOE PAGESBeta

    Das, Sadananda; Oyola, Y.; Mayes, Richard T.; Janke, Christopher James; Kuo, Li-Jung; Gill, Gary; Wood, Jordana; Dai, Sheng

    2015-11-02

    Here, a new family of high surface area polyethylene fiber adsorbents (AF series) was recently developed at the Oak Ridge National Laboratory (ORNL). The AF series of were synthesized by radiation-induced graft polymerization of acrylonitrile and itaconic acid (at different monomer/co-monomer mol ratios) onto high surface area polyethylene fibers. The degree of grafting (%DOG) of AF series adsorbents was found to be 154 354%. The grafted nitrile groups were converted to amidoxime groups by treating with hydroxylamine. The amidoximated adsorbents were then conditioned with 0.44M KOH at 80 C followed by screening at ORNL with simulated seawater spiked with 8more » ppm uranium. Uranium adsorption capacity in simulated seawater screening ranged from 170-200 g-U/kg-ads irrespective of %DOG. A monomer/co-monomer mol ratio in the range of 7.57-10.14 seemed to be optimum for highest uranium loading capacity. Subsequently, the adsorbents were also tested with natural seawater at Pacific Northwest National Laboratory (PNNL) using flow-through exposure uptake experiments to determine uranium loading capacity with varying KOH conditioning time at 80 C. The highest adsorption capacity of AF1 measured after 56 days of marine testing was demonstrated as 3.9 g-U/kg-adsorbent and 3.2 g-U/kg-adsorbent for 1hr and 3hrs of KOH conditioning at 80 C, respectively. Based on capacity values of several AF1 samples, it was observed that changing KOH conditioning from 3hrs to 1hr at 80 C resulted in 22-27% increase in uranium loading capacity in seawater.« less

  10. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... record the focusing of environmental issues. ... 32 National Defense 6 2010-07-01 2010-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form...

  11. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... record the focusing of environmental issues. ... 32 National Defense 6 2011-07-01 2011-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form...

  12. 32 CFR 989.12 - AF Form 813, Request for Environmental Impact Analysis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... record the focusing of environmental issues. ... 32 National Defense 6 2013-07-01 2013-07-01 false AF Form 813, Request for Environmental Impact... FORCE ENVIRONMENTAL PROTECTION ENVIRONMENTAL IMPACT ANALYSIS PROCESS (EIAP) § 989.12 AF Form...

  13. Embossed Teflon AF Laminate Membrane Microfluidic Diaphragm Valves

    NASA Technical Reports Server (NTRS)

    Willis, Peter; Hunt, Brian; White,Victor; Grunthaner, Frank

    2008-01-01

    A microfluidic system has been designed to survive spaceflight and to function autonomously on the Martian surface. It manipulates microscopic quantities of liquid water and performs chemical analyses on these samples to assay for the presence of molecules associated with past or present living processes. This technology lies at the core of the Urey Instrument, which is scheduled for inclusion on the Pasteur Payload of the ESA ExoMars rover mission in 2013. Fabrication processes have been developed to make the microfabricated Teflon-AF microfluidic diaphragm pumps capable of surviving extreme temperature excursions before and after exposure to liquid water. Two glass wafers are etched with features and a continuous Teflon membrane is sandwiched between them (see figure). Single valves are constructed using this geometry. The microfabricated devices are then post processed by heating the assembled device while applying pneumatic pressure to force the Teflon diaphragm against the valve seat while it is softened. After cooling the device, the embossed membrane retains this new shape. This solves previous problems with bubble introduction into the fluid flow where deformations of the membrane at the valve seat occurred during device bonding at elevated temperatures (100-150 C). The use of laminated membranes containing commercial Teflon AF 2400 sheet sandwiched between spun Teflon AF 1600 layers performed best, and were less gas permeable than Teflon AF 1600 membranes on their own. Spinning Teflon AF 1600 solution (6 percent in FLOURINERT(Registered TradeMark) FC40 solvent, 3M Company) at 500 rpm for 1.5 seconds, followed by 1,000 rpm for 3 seconds onto Borofloat glass wafers, results in a 10-micron-thick film of extremely smooth Teflon AF. This spinning process is repeated several times on flat, blank, glass wafers in order to gradually build a thick, smooth membrane. After running this process at least five times, the wafer and Teflon coating are heated under vacuum

  14. Characterization of physically vapor deposited AF2400 thin films

    SciTech Connect

    Chow, R.; Spragge, M.K.; Loomis, G.E.; Rainer, F.; Ward, R.; Thomas, I.M.; Kozlowski, M.R.

    1993-11-01

    Anti-reflective coatings made with Teflon AF2400 had the highest damage thresholds recorded for physical vapor deposited coatings at the Lawrence Livermore National Laboratory damage facility. Physical vapor deposited layers of Teflon AF2400, a perfluorinated amorphous polymer, maintained the bulk optical properties of a high transmittance from 200 nm to 1600 nm, and a low refractive index. In addition, the refractive index can be intentionally reduced by control of two common deposition parameters, deposition rate and substrate temperature. Scanning electron microscopy and nuclear magnetic resonance observations indicated that morphological changes caused the variations in the refractive index rather than compositional changes. The coatings adhered to fused silica and silicon wafers under normal laboratory handling conditions.

  15. Sinuladiterpenes A-F, new cembrane diterpenes from Sinularia flexibilis.

    PubMed

    Lo, Kuang-Liang; Khalil, Ashraf Taha; Kuo, Yao-Haur; Shen, Ya-Ching

    2009-12-01

    Chromatographic investigation of the octocoral Sinularia flexibilis afforded six new cembrane diterpenes, sinuladiterpenes A-F (1-6, resp.), in addition to four known cembranolides, 11-episinulariolide acetate, 11-dehydrosinulariolide, 11-episinulariolide, and sinulariolide. Their structures were elucidated by spectroscopic analysis, especially 2D-NMR and HR-ESI-MS. Compound 2 exhibited significant in vitro cytotoxic activity against human colon adenocarcinoma (WiDr) cell line. PMID:20020460

  16. Durable Superhydrophobic Surfaces via Spontaneous Wrinkling of Teflon AF.

    PubMed

    Scarratt, Liam R J; Hoatson, Ben S; Wood, Elliot S; Hawkett, Brian S; Neto, Chiara

    2016-03-16

    We report the fabrication of both single-scale and hierarchical superhydrophobic surfaces, created by exploiting the spontaneous wrinkling of a rigid Teflon AF film on two types of shrinkable plastic substrates. Sub-100 nm to micrometric wrinkles were reproducibly generated by this simple process, with remarkable control over the size and hierarchy. Hierarchical Teflon AF wrinkled surfaces showed extremely high water repellence (contact angle 172°) and very low contact angle hysteresis (2°), resulting in droplets rolling off the surface at tilt angles lower than 5°. The wrinkling process intimately binds the Teflon AF layer with its substrate, making these surfaces mechanically robust, as revealed by macroscale and nanoscale wear tests: hardness values were close to that of commercial optical lenses and aluminum films, resistance to scratch was comparable to commercial hydrophobic coatings, and damage by extensive sonication did not significantly affect water repellence. By this fabrication method the size of the wrinkles can be reproducibly tuned from the nanoscale to the microscale, across the whole surface in one step; the fabrication procedure is extremely rapid, requiring only 2 min of thermal annealing to produce the desired topography, and uses inexpensive materials. The very low roll-off angles achieved in the hierarchical surfaces offer a potentially up-scalable alternative as self-cleaning and drag-reducing coatings. PMID:26910574

  17. Identification and functional characterization of grass carp IL-17A/F1: An evaluation of the immunoregulatory role of teleost IL-17A/F1.

    PubMed

    Du, Linyong; Feng, Shiyu; Yin, Licheng; Wang, Xinyan; Zhang, Anying; Yang, Kun; Zhou, Hong

    2015-07-01

    In mammals, IL-17A and IL-17F are hallmark cytokines of Th17 cells which act significant roles in eradicating extracellular pathogens. IL-17A and IL-17F homologs nominated as IL-17A/F1-3 have been revealed in fish and their functions remain largely undefined. Here we identified and characterized grass carp IL-17A/F1 (gcIL-17A/F1) in fish immune system. In this regard, both tissue distribution and inductive expression of gcIL-17A/F1 indicated its possible involvement in immune response. Moreover, recombinant gcIL-17A/F1 (rgcIL-17A/F1) was prepared and displayed an ability to enhance pro-inflammatory cytokines (IL-1β, TNF-α and IL-6) mRNA expression in head kidney leukocytes. It is suggestive of that gcIL-17A/F1 may act as a proinflammatory cytokine in fish immunity. Besides, rgcIL-17A/F1 induced gene expression and protein release of grass carp chemokine CXCL-8 (gcCXCL-8) in head kidney cells (HKCs), probably via NF-κB, p38 and Erk1/2 pathways. In particular, culture medium from the HKCs treated by rgcIL-17A/F1 could stimulate peripheral blood leukocytes migration and immunoneutralization of endogenous gcCXCL-8 could partially attenuate this stimulation, suggesting that rgcIL-17A/F1 could recruit immune cells through producing gcCXCL-8 as mammalian IL-17 A and F. Taken together, we not only identified the pro-inflammatory role of gcIL-17A/F1 in host defense, but also provided the basis for clarifying Th17 cells in teleost. PMID:25847875

  18. Penarines A-F, (nor-)sesquiterpene carboxylic acids from Hygrophorus penarius (Basidiomycetes).

    PubMed

    Otto, Alexander; Porzel, Andrea; Schmidt, Jürgen; Wessjohann, Ludger; Arnold, Norbert

    2014-12-01

    Five sesquiterpene carboxylic acids (1-5) and one nor-sesquiterpene carboxylic acid (6) of the very rare ventricosane type, named penarines A-F, were isolated from fruiting bodies of the basidiomycete Hygrophorus penarius (Hygrophoraceae). This is the first report of (nor)-sesquiterpenes isolated from basidiocarps of the family Hygrophoraceae. Their structures were elucidated on the basis of extensive 1D ((1)H, (13)C) and 2D (HSQC, HMBC, COSY, ROESY) NMR spectroscopic analyses as well as high-resolution mass spectrometry studies. Additionally, the only known member of this rare type of sesquiterpenes, ventricos-7(13)-ene (7), could be identified via headspace GC-MS analysis in a fruiting body of H. penarius. Compounds 1-6 were devoid of remarkable antifungal activity against Cladosporium cucumerinum. Additionally, the cytotoxic activities of compounds 1 and 2 were evaluated against the human prostate cancer cell line PC-3 and the colon cancer cell line HT-29 showing no significant cytotoxic activity. PMID:25269661

  19. Atrial Fibrillation is Associated With Morphine Treatment in Female Breast Cancer Patients

    PubMed Central

    Lee, Cynthia Wei-Sheng; Muo, Chih-Hsin; Liang, Ji-An; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract We investigated the relationship between morphine treatment and the risk of atrial fibrillation (AF) in female patients with breast cancer. We identified a malignancy cohort of 73,917 female breast cancer patients without an AF history before the date of breast cancer diagnosis between 2000 and 2010 by using the Longitudinal Health Insurance Database for Catastrophic Illness Patients in Taiwan. This malignancy cohort was divided into morphine and comparison cohorts comprising 18,671 and 55,246 patients, respectively, and the incidences of newly diagnosed AF were calculated. We used the Cox proportional hazard model with time-dependent exposure covariates to estimate the risk of AF. The effect of morphine was assessed through multivariable Cox proportional hazard regression controlling for age, the Charlson comorbidity index (CCI) score, and the use of bisphosphonates and paclitaxel. Compared with nonmorphine users, patients who received morphine exhibited a 4.37-fold (95% CI = 3.56–5.36) increase in the risk of developing AF. The risk of AF increased as the CCI score increased, but decreased in patients with tamoxifen treatment. This risk is especially significant in current morphine users of all ages and with low CCI score. AF risk increased as the duration of morphine use lengthened (P for trend <0.0001). The incidence of AF in female breast cancer patients in Taiwan is associated with morphine, but prevented by tamoxifen treatment. PMID:26986153

  20. Binding sites for two novel phosphoproteins, 3AF5 and 3AF3, are required for rbcS-3A expression.

    PubMed Central

    Sarokin, L P; Chua, N H

    1992-01-01

    Previous studies of boxes II (-151 to -138) and III (-125 to -114), binding sites for the nuclear factor GT-1 within the -166 deleted promoter of the ribulose-1,5-bisphosphate carboxylase-3A (rbcS-3A) gene, suggested that GT-1 might act in concert with an additional protein to confer light-responsive rbcS-3A expression. In this work, S1 analysis of RNA isolated from transgenic tobacco plants carrying mutant rbcS-3A constructs led to the identification of two short sequences located at the 5' and 3' ends of box III that are required for expression. These two sequences serve as binding sites for two novel proteins, 3AF5 and 3AF3. Gel shift studies using tetramerized binding sites for both 3AF5 and 3AF3 showed that complexes with faster mobilities were formed using nuclear extracts prepared from dark-adapted plants compared with those from light-grown tobacco plants. Phosphatase treatment of extracts from light-grown plants resulted in the formation of complexes with faster mobility. Although the binding of 3AF3 to its target site is dependent upon phosphorylation, the binding of 3AF5 does not appear to be affected by its phosphorylation state. These results suggest that the phosphorylated forms of both 3AF5 and 3AF3 are required for -166 rbcS-3A expression but that the mechanisms differ by which phosphorylation regulates the activities of 3AF5 and 3AF3. PMID:1498605

  1. The Advancing State of AF-M315E Technology

    NASA Technical Reports Server (NTRS)

    Masse, Robert; Spores, Ronald A.; McLean, Chris

    2014-01-01

    The culmination of twenty years of applied research in hydroxyl ammonium nitrate (HAN)-based monopropellants, the NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) will achieve the first on-orbit demonstration of an operational AF-M315E green propellant propulsion system by the end of 2015. Following an contextual overview of the completed flight design of the GPIM propellant storage and feed system, results of first operation of a flight-representative heavyweight 20-N engineering model thruster (to be conducted in mid-2014) are presented with performance comparisons to prior lab model (heavyweight) test articles.

  2. RX-26-AY/AF rifle bullet tests

    SciTech Connect

    Sharp, D.D.

    1980-11-01

    A series of rifle bullet tests was performed on two explosives, RX-26-AY and RX-26-AF, using the Pantex version of the Picatinny Arsenal Test (PA-2). With the exception of one test, both explosives displayed a relatively low sensitivity to bullet impact. However, a marked difference was noted in the average burn time duration between the two types of explosives being tested. A minor modification was made on the rifle barrel used at the test site in order to improve the sighting procedure.

  3. NMR study of the AF-SC-SC-AF phased transition in a pnictide superconductor LaFeAsO1-xHx

    NASA Astrophysics Data System (ADS)

    Fujiwara, Naoki; Sakurai, Ryosuke; Iimura, Soushi; Matsuishi, Satoru; Hosono, Hideo; Yamakawa, Youichi; Kontani, Hiroshi

    2014-03-01

    We have performed 75As and 1H NMR measurements in LaFeAsO1xHx, an isomorphic compound of LaFeAsO1xFx. LaFeAsO1xHx is an electron doped system, and O2- can be replaced with H- up to x = 0.5. LaFeAsO1xHx is known for having double superconducting (SC) domes on H doping. Recently, we discovered that a new antiferromagnetic (AF) phase follows the double SC domes on further H doping, forming a symmetric AF-SC-SC-AF phase alignment in the electronic phase diagram Unlike the AF ordering in the lightly H-doped regime, the AF ordering in the highly H-doped regime is attributed to the nesting between electron pockets. In the conference, we will show the data of both NMR spectra and the relaxation rate 1/T1 in the whole doping region. We will discuss the difference of electronic states between the lightly H-doped AF-SC phases and highly H-doped SC-AF phases. This work is supported by a Grant-in-Aid (Grant No. KAKENHI 23340101) from the Ministry of Education, Science, and Culture, Japan.

  4. AFS men and women differ most in their lifestyle choices

    USGS Publications Warehouse

    Connelly, N.A.; Brown, T.L.; Hardiman, J.M.

    2006-01-01

    The American Fisheries Society sponsored a survey to examine the career development choices of men and women and how they might differ by gender. A random sample of 700 men and 700 women was selected from the AFS membership database. The survey was mailed out in October 2004 and 991 questionnaires were returned for an adjusted response rate of 71%. Some differences exist between men and women in the areas of interest development, education, and employment, but the substantive differences occur in lifestyle choices. Women with a fisheries career are less likely to be married than men, even when age is controlled for, and women who are married are more likely to have dual-career considerations than their male counterparts. Among respondents without dependents in their home during their professional career, twice as many women as men think having children will adversely affect their career. For those with dependents, more than twice as many women as men said they had to put their career "on hold" because of their dependents. While AFS members do not represent all members of the fisheries profession, their experiences shed substantial light on the lifestyle choices likely faced by most members of the profession.

  5. Identification and characterization of the afsR homologue regulatory gene from Streptomyces peucetius ATCC 27952.

    PubMed

    Parajuli, Niranjan; Viet, Hung Trinh; Ishida, Kenji; Tong, Hang Thi; Lee, Hei Chan; Liou, Kwangkyoung; Sohng, Jae Kyung

    2005-01-01

    We have isolated an afsR homologue, called afsR-p, through genome analysis of Streptomyces peucetius ATCC 27952. AfsR-p shares 60% sequence identity with AfsR from Streptomyces coelicolor A3 (2). afsR-p was expressed under the control of the ermE* promoter in its hosts S. peucetius, Streptomyces lividans TK 24, Streptomyces clavuligerus and Streptomyces griseus. We observed overproduction of doxorubicin (4-fold) in S. peucetius, gamma-actinorhodin (2.6-fold) in S. lividans, clavulanic acid (1.5-fold) in S. clavuligerus and streptomycin (slight) in S. griseus. Overproduction was due to expression of the gene in these strains as compared to the wild-type strains harboring the vector only. Comparative study of the expression of afsR-p revealed that regulatory networking in Streptomyces is not uniform. We speculate that phosphorylated AfsR-p becomes bound to the promoter region of afsS. The latter activates other regulatory genes, including pathway regulatory genes, and induces the production of secondary metabolites including antibiotics. We identified specific conserved amino acids and exploited them for the isolation of the partial sequence of the afsR homologue from S. clavuligerus and Streptomyces achromogens (rubradirin producer). Such findings provide additional evidence for the presence of a serine/threonine and tyrosine kinase-dependent global regulatory network in Streptomyces. PMID:15921897

  6. Dual Function for U2AF35 in AG-Dependent Pre-mRNA Splicing

    PubMed Central

    Guth, Sabine; Tange, Thomas O/.; Kellenberger, Esther; Valcárcel, Juan

    2001-01-01

    The splicing factor U2AF is required for the recruitment of U2 small nuclear RNP to pre-mRNAs in higher eukaryotes. The 65-kDa subunit of U2AF (U2AF65) binds to the polypyrimidine (Py) tract preceding the 3′ splice site, while the 35-kDa subunit (U2AF35) contacts the conserved AG dinucleotide at the 3′ end of the intron. It has been shown that the interaction between U2AF35 and the 3′ splice site AG can stabilize U2AF65 binding to weak Py tracts characteristic of so-called AG-dependent pre-mRNAs. U2AF35 has also been implicated in arginine-serine (RS) domain-mediated bridging interactions with splicing factors of the SR protein family bound to exonic splicing enhancers (ESE), and these interactions can also stabilize U2AF65 binding. Complementation of the splicing activity of nuclear extracts depleted of U2AF by chromatography in oligo(dT)-cellulose requires, for some pre-mRNAs, only the presence of U2AF65. In contrast, splicing of a mouse immunoglobulin M (IgM) M1-M2 pre-mRNA requires both U2AF subunits. In this report we have investigated the sequence elements (e.g., Py tract strength, 3′ splice site AG, ESE) responsible for the U2AF35 dependence of IgM. The results indicate that (i) the IgM substrate is an AG-dependent pre-mRNA, (ii) U2AF35 dependence correlates with AG dependence, and (iii) the identity of the first nucleotide of exon 2 is important for U2AF35 function. In contrast, RS domain-mediated interactions with SR proteins bound to the ESE appear to be dispensable, because the purine-rich ESE present in exon M2 is not essential for U2AF35 activity and because a truncation mutant of U2AF35 consisting only of the pseudo-RNA recognition motif domain and lacking the RS domain is active in our complementation assays. While some of the effects of U2AF35 can be explained in terms of enhanced U2AF65 binding, other activities of U2AF35 do not correlate with increased cross-linking of U2AF65 to the Py tract. Collectively, the results argue that

  7. MLL-AF9 Expression in Hematopoietic Stem Cells Drives a Highly Invasive AML Expressing EMT-Related Genes Linked to Poor Outcome.

    PubMed

    Stavropoulou, Vaia; Kaspar, Susanne; Brault, Laurent; Sanders, Mathijs A; Juge, Sabine; Morettini, Stefano; Tzankov, Alexandar; Iacovino, Michelina; Lau, I-Jun; Milne, Thomas A; Royo, Hélène; Kyba, Michael; Valk, Peter J M; Peters, Antoine H F M; Schwaller, Juerg

    2016-07-11

    To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition (EMT) in solid cancers. Knockdown of the EMT regulator ZEB1 significantly reduced leukemic blast invasion. By classifying mouse and human leukemias according to Evi1/EVI1 and Erg/ERG expression, reflecting aggressiveness and cell of origin, and performing comparative transcriptomics, we identified several EMT-related genes that were significantly associated with poor overall survival of AML patients. PMID:27344946

  8. Transient potential receptor melastatin-2 (Trpm2) does not influence murine MLL-AF9-driven AML leukemogenesis or in vitro response to chemotherapy.

    PubMed

    Haladyna, Jessica N; Pastuer, Taylor; Riedel, Simone S; Perraud, Anne-Laure; Bernt, Kathrin M

    2016-07-01

    Transient potential receptor melastatin-2 (TRPM2) is a nonselective cationic, Ca(2+)-permeable transmembrane pore that is preferentially expressed in cells of the myeloid lineage and modulates signaling pathways converging into NF-kB. This is of potential interest for acute myeloid leukemia (AML) therapy, as NF-κB signaling is emerging as a key pathway, mediating drug resistance and leukemia-initiating cell survival in AML. Inhibition of NF-κB signaling has been found to be synergistic with chemotherapy. TRPM2 is overexpressed in AML compared with normal bone marrow, with the highest levels in the FAB M3-6 subtypes. To determine the effect of TRPM2 depletions in a defined genetic model, we established MLL-AF9-driven AML on a Trpm2(-/-) genetic background. Trpm2(-/-) MLL-AF9 leukemias displayed reduced NF-κB phosphorylation as well as nuclear translocation. In vivo, primary and secondary recipients of Trpm2(-/-) MLL-AF9 leukemias exhibit increased latency compared with recipients of wild-type leukemia cells. However, the difference in latency was small and was lost in tertiary transplants. The effect of loss of Trpm2 in a BCR-ABL/NUP98-HOXA9 fusion model was even smaller. Given reports that loss or inhibition of TRPM2 enhanced killing by DNA-damaging agents in neuroblastoma, breast cancer, and prostate cancer cell lines, we exposed Trpm2(-/-) and Trpm2(wt) primary MLL-AF9 leukemias to doxorubicin, cytarabine, and etoposide, but found no difference in IC50 values. The in vitro response to decitabine was also unaffected. In summary, Trpm2 does not seem to play a major role in myeloid leukemogenesis. Additionally, loss of Trpm2 does not augment the cytotoxicity of standard AML chemotherapeutic agents. PMID:27033163

  9. Pharmacokinetics of cefaclor AF: effects of age, antacids and H2-receptor antagonists.

    PubMed

    Satterwhite, J H; Cerimele, B J; Coleman, D L; Hatcher, B L; Kisicki, J; DeSante, K A

    1992-01-01

    The pharmacokinetics and bioavailability of cefaclor advanced formulation (cefaclor AF) were investigated in two studies, one comparing healthy elderly and younger volunteers and the other assessing the effects of an antacid and H2-receptor antagonist on cefaclor AF bioavailability. The pharmacokinetics of a 750 mg dose of cefaclor AF were studied in 30 subjects ranging in age from 65 to 84 years and 10 control subjects 21-45 years of age. Compared with controls, elderly subjects exhibited higher plasma concentrations of cefaclor which were attributed to lower plasma clearance. There was a strong association between age and renal function, and the plasma clearance of cefaclor was highly dependent upon renal function. Thus, elderly patients with impaired renal function had a reduced ability to eliminate cefaclor. Due to a short elimination half-life and wide therapeutic index, dosage adjustments are not necessary in patients exhibiting moderate renal dysfunction. The 15 healthy men in the second trial were crossed over to receive five treatments, including cefaclor AF (500 mg) alone, cefaclor AF with or preceded by cimetidine, cefaclor AF followed by Maalox TC and cefaclor immediate release (500 mg) alone. Cefaclor AF and immediate release cefaclor had similar bioavailability, but plasma concentrations were maintained for a longer period of time when cefaclor AF was administered. Cimetidine did not alter the bioavailability of cefaclor AF but Maalox TC, coadministered with cefaclor AF, reduced the extent of absorption. This suggests that cefaclor AF bioavailability is influenced by the antacid Maalox TC but not by H2-receptor antagonist cimetidine. PMID:1287615

  10. Penipyridones A-F, Pyridone Alkaloids from Penicillium funiculosum.

    PubMed

    Zhou, Haibo; Li, Liyuan; Wu, Chongming; Kurtán, Tibor; Mándi, Attila; Liu, Yankai; Gu, Qianqun; Zhu, Tianjiao; Guo, Peng; Li, Dehai

    2016-07-22

    Six new pyridone alkaloids, named penipyridones A-F (1-6), were isolated from the fermentation broth of an Antarctic moss-derived fungus, Penicillium funiculosum GWT2-24. Their structures were elucidated from extensive NMR and MS data. Although they possess the same major chromophore and some of them presented almost mirror ECD spectra, their absolute configurations were found to be uniformly S, as evidenced by X-ray single-crystal diffraction analysis, stereocontrolled total synthesis, and chemical conversions. TDDFT-ECD calculations of compounds 3 and 6 revealed that subtle conformational changes are responsible for the significantly different ECD curves. None of the compounds were cytotoxic (IC50 > 50 μM), while compounds 1, 2, 5, and 7 elicited lipid-lowering activity in HepG2 hepatocytes. PMID:27359163

  11. Optimised secure transmission through untrusted AF relays using link adaptation

    NASA Astrophysics Data System (ADS)

    Taki, Mehrdad; Sadeghi, Mohammad

    2016-05-01

    A new transmission scheme is presented for a two-hop relay network including two AF relays, considering physical layer security where relays are not able to detect signal with an acceptable bit error rate (BER) but the combined received signal is detected with an acceptable BER at the final receiver. It is assumed that there is no direct path between the transmitter and the receiver (relay network without diversity). Adaptive modulation and coding is utilised at the transmitter and transmission powers of the transmitter and of the relays are continuously adapted provisioning individual average power constraint for each node. Numerical evaluations show that an acceptable performance degradation is seen by the proposed secure relaying scheme compared to the optimum relay selection scheme without security constraint.

  12. Association between Postoperatively Developed Atrial Fibrillation and Long-Term Mortality after Esophagectomy in Esophageal Cancer Patients: An Observational Study

    PubMed Central

    Chin, Ji-Hyun; Moon, Young-Jin; Jo, Jun-Young; Han, Yun A.; Kim, Hyeong Ryul; Choi, In-Cheol

    2016-01-01

    Background Newly developed atrial fibrillation (AF) in patients who have undergone an esophagectomy increases the incidence of postoperative complications. However, the clinical implications of AF have not been fully elucidated in these patients. This retrospective observational study investigated the predictors for AF and the effect of AF on the mortality in esophageal cancer patients undergoing esophagectomy. Methods This study evaluated 583 patients undergoing esophagectomy, from January 2005 to April 2012. AF was defined as newly developed postoperative AF requiring treatment. The risk factors for AF and the association between AF and mortality were evaluated. The long-term mortality was the all-cause mortality, for which the cutoff date was May 31, 2014. Results AF developed in 63 patients (10.8%). Advanced age (odds ratio [OR] 1.099, 95% confidence interval [CI] 1.056–1.144, P < 0.001), preoperative calcium channel blocker (CCB) (OR 2.339, 95% CI 1.143–4.786, P = 0.020), and angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) (OR 0.206, 95% CI 0.067–0.635, P = 0.006) were associated with the incidence of AF. The Kaplan-Meier curve showed a significantly lower survival rate in the AF group compared to the non-AF group (P = 0.045), during a median follow-up of 50.7 months. The multivariable analysis revealed associations between AF and the 1-year mortality (hazard ratio [HR] 2.556, 95% CI 1.430–4.570, P = 0.002) and between AF and the long-term mortality (HR 1.507, 95% CI 1.003–2.266, P = 0.049). Conclusions In esophageal cancer patients, the advanced age and the preoperative medications (CCB, ACEI or ARB) were associated with the incidence of AF. Furthermore, postoperatively developed AF was associated with mortality in esophageal cancer patients after esophagectomy, suggesting that a close surveillance might be required in patients who showed AF during postoperative period. PMID:27148877

  13. Evaluation of the atoxigenic Aspergillus flavus strain AF36 in pistachio orchards

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The atoxigenic strain Aspergillus flavus AF36, which has been extensively used as a biocontrol agent in commercial corn and cotton fields to reduce aflatoxin contamination, was applied in research pistachio orchards from 2002 to 2005 and in commercial pistachio orchards from 2008 to 2011. AF36 was a...

  14. Mutant U2AF1 Expression Alters Hematopoiesis and Pre-mRNA Splicing In Vivo

    PubMed Central

    Shirai, Cara Lunn; Ley, James N.; White, Brian S.; Kim, Sanghyun; Tibbitts, Justin; Shao, Jin; Ndonwi, Matthew; Wadugu, Brian; Duncavage, Eric J.; Okeyo-Owuor, Theresa; Liu, Tuoen; Griffith, Malachi; McGrath, Sean; Magrini, Vincent; Fulton, Robert S.; Fronick, Catrina; O’Laughlin, Michelle; Graubert, Timothy A.; Walter, Matthew J.

    2015-01-01

    SUMMARY Heterozygous somatic mutations in the spliceosome gene U2AF1 occur in ~11% of patients with myelodysplastic syndromes (MDS), the most common adult myeloid malignancy. It is unclear how these mutations contribute to disease. We examined in vivo hematopoietic consequences of the most common U2AF1 mutation using a doxycycline-inducible transgenic mouse model. Mice expressing mutant U2AF1(S34F) display altered hematopoiesis and changes in pre-mRNA splicing in hematopoietic progenitor cells by whole transcriptome analysis (RNA-seq). Integration with human RNA-seq datasets determined that common mutant U2AF1-induced splicing alterations are enriched in RNA processing genes, ribosomal genes, and recurrently-mutated MDS and acute myeloid leukemia-associated genes. These findings support the hypothesis that mutant U2AF1 alters downstream gene isoform expression, thereby contributing to abnormal hematopoiesis in MDS patients. PMID:25965570

  15. Cancer Basics

    MedlinePlus

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  16. Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

    PubMed Central

    Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  17. Biotransformation of bisphenol AF to its major glucuronide metabolite reduces estrogenic activity.

    PubMed

    Li, Ming; Yang, Yunjia; Yang, Yi; Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  18. Atrial Fibrillation Management Strategies in Routine Clinical Practice: Insights from the International RealiseAF Survey

    PubMed Central

    Chiang, Chern-En; Naditch-Brûlé, Lisa; Brette, Sandrine; Silva-Cardoso, José; Gamra, Habib; Murin, Jan; Zharinov, Oleg J.; Steg, Philippe Gabriel

    2016-01-01

    Background Atrial fibrillation (AF) can be managed with rhythm- or rate-control strategies. There are few data from routine clinical practice on the frequency with which each strategy is used and their correlates in terms of patients’ clinical characteristics, AF control, and symptom burden. Methods RealiseAF was an international, cross-sectional, observational survey of 11,198 patients with AF. The aim of this analysis was to describe patient profiles and symptoms according to the AF management strategy used. A multivariate logistic regression identified factors associated with AF management strategy at the end of the visit. Results Among 10,497 eligible patients, 53.7% used a rate-control strategy, compared with 34.5% who used a rhythm-control strategy. In 11.8% of patients, no clear strategy was stated. The proportion of patients with AF-related symptoms (EHRA Class > = II) was 78.1% (n = 4396/5630) for those using a rate-control strategy vs. 67.8% for those using a rhythm-control strategy (p<0.001). Multivariate logistic regression analysis revealed that age <75 years or the paroxysmal or persistent form of AF favored the choice of a rhythm-control strategy. A change in strategy was infrequent, even in patients with European Heart Rhythm Association (EHRA) Class > = II. Conclusions In the RealiseAF routine clinical practice survey, rate control was more commonly used than rhythm control, and a change in strategy was uncommon, even in symptomatic patients. In almost 12% of patients, no clear strategy was stated. Physician awareness regarding optimal management strategies for AF may be improved. PMID:26800084

  19. Versixanthones A-F, Cytotoxic Xanthone-Chromanone Dimers from the Marine-Derived Fungus Aspergillus versicolor HDN1009.

    PubMed

    Wu, Guangwei; Yu, Guihong; Kurtán, Tibor; Mándi, Attila; Peng, Jixing; Mo, Xiaomei; Liu, Ming; Li, Hui; Sun, Xinhua; Li, Jing; Zhu, Tianjiao; Gu, Qianqun; Li, Dehai

    2015-11-25

    Six unusual xanthone-chromanone dimers, versixanthones A-F (1-6), featuring different formal linkages of tetrahydroxanthone and 2,2-disubstituted chroman-4-one monomers, were isolated from a culture of the mangrove-derived fungus Aspergillus versicolor HDN1009. The absolute configurations of 1-6, representing the central and axial chirality elements or preferred helicities, were established by a combination of X-ray diffraction analysis, chemical conversions, and TDDFT-ECD calculations. The interconversion of different biaryl linkages between 1 and 4 and between 2 and 3 in DMSO by a retro-oxa-Michael mechanism provided insight into the formation of the xanthone-chromanone dimers and supported the assignments of their absolute configurations. Compounds 1-6 exhibited cytotoxicities against the seven tested cancer cell lines, with the best IC50 value of 0.7 μM. Compound 5 showed further inhibitory activity against topoisomerase I. PMID:26506221

  20. Hsp90 Directly Modulates the Spatial Distribution of AF9/MLLT3 and Affects Target Gene Expression*

    PubMed Central

    Lin, Jeffrey J.; Hemenway, Charles S.

    2010-01-01

    AF9/MLLT3 contributes to the regulation of the gene encoding the epithelial sodium channel α, ENaCα, in renal tubular cells. Specifically, increases in AF9 protein lead to a reduction in ENaCα expression and changes in AF9 activity appear to be an important component of aldosterone signaling in the kidney. Whereas AF9 is found in the nucleus where it interacts with the histone H3 lysine 79 methyltransferase, Dot1, AF9 is also present in the cytoplasm. Data presented in this report indicate that the heat shock protein Hsp90 directly and specifically interacts with AF9 as part of an Hsp90-Hsp70-p60/Hop chaperone complex. Experimental manipulation of Hsp90 function by the inhibitor novobiocin, but not 17-AAG, results in redistribution of AF9 from a primarily nuclear to cytoplasmic location. Knockdown of Hsp90 with siRNA mimics the effect elicited by novobiocin. As expected, a shift in AF9 from the nucleus to the cytoplasm in response to Hsp90 interference leads to increased ENaCα expression. This is accompanied by a decrease in AF9 occupancy at the ENaCα promoter. Our data suggest that the interaction of Hsp90, Hsp70, and p60/Hop with AF9 is necessary for the proper subnuclear localization and activity of AF9. AF9 is among a growing number of nuclear proteins recognized to rely on the Hsp90 complex for nuclear targeting. PMID:20159978

  1. [Factor AF2--the 4th column in tumor therapy. Documentation No.22].

    PubMed

    Kast, A; Hauser, S P

    1990-04-17

    Factor AF2 is an extract from the spleen and liver of sheep embryos and lambs. The product contains biotechnologically produced, chromatographically uniform, molecularly standardized polypeptides, glycopeptides, glycolipids and nucleotides, deproteinized and free of pyrogens'. Factor AF2 is intended mainly for use in 'supportive antitumour therapy', as a 'biological antiemetic and analgesic'. The proposed duration of treatment is usually more than six months. The dosage varies considerably according to the indication. The average daily costs are, therefore, between DM 4.- (prevention of recurrence) and DM 107.- (adjuvant to chemotherapy). Allergic reactions have been reported in 'rare cases'. Factor AF2 was developed in the forties by Guarnieri in Rome. Since 1984, Factor AF2 is 'biotechnologically' produced and as a 'biological response modifier' (BRM) in the oncotherapy distributed by Biosyn Arzneimittel GmbH, Stuttgart. Dr. rer. nat. T. Stiefel and Dr. rer. nat. H. Porcher are the representatives of Biosyn Arzneimittel GmbH. In the past, both worked with Vitorgan Arzneimittel GmbH (cytoplasmatic therapy according to Theurer). It is claimed that Factor AF2 contains 'immunomodulating and immunorestorative biomolecules' assignable to the BRM group. Terms and investigations from current immunological research are applied to Factor AF2. No preclinical investigations are available which demonstrate any cytostatic effect of Factor AF2. In vivo, no effects were observed on the transplanted meth-A-sarcoma in mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2349412

  2. The Ras Target AF-6 is a Substrate of the Fam Deubiquitinating Enzyme

    PubMed Central

    Taya, Shinichiro; Yamamoto, Takaharu; Kano, Kyoko; Kawano, Yoji; Iwamatsu, Akihiro; Tsuchiya, Tomoko; Tanaka, Keiji; Kanai-Azuma, Masami; Wood, Stephen A.; Mattick, John S.; Kaibuchi, Kozo

    1998-01-01

    The Ras target AF-6 has been shown to serve as one of the peripheral components of cell–cell adhesions, and is thought to participate in cell–cell adhesion regulation downstream of Ras. We here purified an AF-6-interacting protein with a molecular mass of ∼220 kD (p220) to investigate the function of AF-6 at cell–cell adhesions. The peptide sequences of p220 were identical to the amino acid sequences of mouse Fam. Fam is homologous to a deubiquitinating enzyme in Drosophila, the product of the fat facets gene. Recent genetic analyses indicate that the deubiquitinating activity of the fat facets product plays a critical role in controlling the cell fate. We found that Fam accumulated at the cell–cell contact sites of MDCKII cells, but not at free ends of plasma membranes. Fam was partially colocalized with AF-6 and interacted with AF-6 in vivo and in vitro. We also showed that AF-6 was ubiquitinated in intact cells, and that Fam prevented the ubiquitination of AF-6. PMID:9722616

  3. Critical behavior of a triangular lattice Ising AF/FM bilayer

    NASA Astrophysics Data System (ADS)

    Žukovič, M.; Bobák, A.

    2016-03-01

    We study a bilayer Ising spin system consisting of antiferromagnetic (AF) and ferromagnetic (FM) triangular planes, coupled by ferromagnetic exchange interaction, by standard Monte Carlo and parallel tempering methods. The AF/FM bilayer is found to display the critical behavior completely different from both the single FM and AF constituents as well as the FM/FM and AF/AF bilayers. Namely, by finite-size scaling (FSS) analysis we identify at the same temperature a standard Ising transition from the paramagnetic to FM state in the FM plane that induces a ferrimagnetic state with a finite net magnetic moment in the AF plane. At lower temperatures there is another phase transition, that takes place only in the AF plane, to different ferrimagnetic state with spins on two sublattices pointing parallel and on one sublattice antiparallel to the spins on the FM plane. FSS indicates that the corresponding critical exponents are close to the two-dimensional three-state ferromagnetic Potts model values.

  4. U2AF1 Mutations Alter Sequence Specificity of pre-mRNA Binding and Splicing

    PubMed Central

    Okeyo-Owuor, Theresa; White, Brian S.; Chatrikhi, Rakesh; Mohan, Dipika R.; Kim, Sanghyun; Griffith, Malachi; Ding, Li; Ketkar-Kulkarni, Shamika; Hundal, Jasreet; Laird, Kholiswa M.; Kielkopf, Clara L.; Ley, Timothy J.; Walter, Matthew J.; Graubert, Timothy A.

    2014-01-01

    We previously identified missense mutations in the U2AF1 splicing factor affecting codons S34 (S34F and S34Y) or Q157 (Q157R and Q157P) in 11% of patients with de novo myelodysplastic syndromes (MDS). Although the role of U2AF1 as an accessory factor in the U2 snRNP is well established, it is not yet clear how mutations affect splicing or contribute to MDS pathophysiology. We analyzed splice junctions in RNA-seq data generated from transfected CD34+ hematopoietic cells and found significant differences in the abundance of known and novel junctions in samples expressing mutant U2AF1 (S34F). For selected transcripts, splicing alterations detected by RNA-seq were confirmed by analysis of primary de novo MDS patient samples. These effects were not due to impaired U2AF1 (S34F) localization as it co-localized normally with U2AF2 within nuclear speckles. We further found evidence in the RNA-seq data for decreased affinity of U2AF1 (S34F) for uridine (relative to cytidine) at the e-3 position immediately upstream of the splice acceptor site and corroborated this finding using affinity binding assays. These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis. PMID:25311244

  5. Ternary complex formation and competition quench fluorescence of ZnAF family zinc sensors.

    PubMed

    Staszewska, Anna; Kurowska, Ewa; Bal, Wojciech

    2013-11-01

    Our current understanding of the intracellular thermodynamics and kinetics of Zn(ii) ions is largely based on the application of fluorescent sensor molecules, used to study and visualize the concentration, distribution and transport of Zn(ii) ions in real time. Such agents are designed for high selectivity for zinc in respect to other biological metal ions. However, the issue of their sensitivity to physiological levels of low molecular weight Zn(ii) ligands (LMWLs) has not been addressed. We followed the effects of eight such compounds on the fluorescence of ZnAF-1 and ZnAF-2F, two representatives of the ZnAF family of fluorescein-based zinc sensors containing the N,N-bis(2-pyridylmethyl)ethylenediamine chelating unit. Fluorescence titrations of equimolar Zn(ii)-ZnAF-1 and Zn(ii)-ZnAF-2F solutions with acetate, phosphate, citrate, glycine, glutamic acid, histidine, ATP and GSH demonstrated strong fluorescence quenching. These results are interpreted in terms of an interplay of the formation of the [ZnAF-Zn(ii)-LMWL] ternary complexes and the competition for Zn(ii) between ZnAF and LMWLs. UV-vis spectroscopic titrations revealed the existence of supramolecular interactions between the fluorescein moiety of ZnAF-1 and ATP and His, which, however, did not contribute to fluorescence quenching. Therefore, the obtained results show that the ZnAF sensors, other currently used zinc sensors containing the N,N-bis(2-pyridylmethyl)ethylenediamine unit, and, in general, all sensors that do not saturate the Zn(ii) coordination sphere may co-report cellular metabolites and Zn(ii) ions, leading to misrepresentations of the concentrations and fluxes of biological zinc. PMID:23939683

  6. Hospitalizations in patients with atrial fibrillation: an analysis from ROCKET AF

    PubMed Central

    DeVore, Adam D.; Hellkamp, Anne S.; Becker, Richard C.; Berkowitz, Scott D.; Breithardt, Guenter; Hacke, Werner; Halperin, Jonathan L.; Hankey, Graeme J.; Mahaffey, Kenneth W.; Nessel, Christopher C.; Singer, Daniel E.; Fox, Keith A. A.; Patel, Manesh R.; Piccini, Jonathan P.

    2016-01-01

    Aims The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. Methods and results The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29–1.66], diabetes [1.22, (1.11–1.34)], prior MI [1.27, (1.13–1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04–1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. Conclusion Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization. PMID:27174904

  7. Colorectal Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Hindi (हिन्दी) Japanese (日本語) Korean (한국어) Portuguese (português) Russian (Русский) Somali (af Soomaali) Spanish (español) Tagalog ( ... 한국어 (Korean) Bilingual PDF Health Information Translations Portuguese (português) Cancer of the Colon and Rectum Câncer do ...

  8. The Inhibition of Inflammasome by Brazilian Propolis (EPP-AF)

    PubMed Central

    Hori, Juliana I.; Zamboni, Dario S.; Carrão, Daniel B.; Goldman, Gustavo Henrique; Berretta, Andresa A.

    2013-01-01

    Propolis extracts have gained the attention of consumers and researchers due to their unique chemical compositions and functional properties such as its anti-inflammatory activity. Recently, it was described a complex that is also important in inflammatory processes, named inflammasome. The inflammasomes are a large molecular platform formed in the cell cytosol in response to stress signals, toxins, and microbial infections. Once activated, the inflammasome induces caspase-1, which in turn induces the processing of inflammatory cytokines such as IL-1β and IL-18. So, to understand inflammasomes regulation becomes crucial to treat several disorders including autoinflammatory diseases. Since green propolis extracts are able to regulate inflammatory pathways, this work purpose was to investigate if this extract could also act on inflammasomes regulation. First, the extract was characterized and it demonstrated the presence of important compounds, especially Artepillin C. This extract was effective in reducing the IL-1β secretion in mouse macrophages and this reduction was correlated with a decrease in activation of the protease caspase-1. Furthermore, we found that the extract at a concentration of 30 μg/mL was not toxic to the cells even after a 18-hour treatment. Altogether, these data indicate that Brazilian green propolis (EPP-AF) extract has a role in regulating the inflammasomes. PMID:23690844

  9. Flacourtosides A-F, phenolic glycosides isolated from Flacourtia ramontchi.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Eydoux, Cécilia; Guillemot, Jean-Claude; Canard, Bruno; Rasoanaivo, Philippe; Guéritte, Françoise; Litaudon, Marc

    2012-04-27

    In an effort to identify novel inhibitors of chikungunya (CHIKV) and dengue (DENV) virus replication, a systematic study with 820 ethyl acetate extracts of madagascan plants was performed in a virus-cell-based assay for CHIKV, and a DENV NS5 RNA-dependent RNA polymerase (RdRp) assay. The extract obtained from the stem bark of Flacourtia ramontchi was selected for its significant activity in both assays. Six new phenolic glycosides, named flacourtosides A-F (1-6), phenolic glycosides itoside H, xylosmin, scolochinenoside D, and poliothrysoside, and betulinic acid 3β-caffeate were obtained using the bioassay-guided isolation process. Their structures were elucidated by comprehensive analyses of NMR spectroscopic and mass spectrometric data. Even though several extracts and fractions showed significant selective antiviral activity in the CHIKV virus-cell-based assay, none of the purified compounds did. However, in the DENV RNA polymerase assay, significant inhibition was observed with betulinic acid 3β-caffeate (IC(50) = 0.85 ± 0.1 μM) and to a lesser extent for the flacourtosides A and E (1 and 5, respectively), and scolochinenoside D (IC(50) values ~10 μM). PMID:22439591

  10. Cancer - Multiple Languages: MedlinePlus

    MedlinePlus

    ... न्दी) Japanese (日本語) Khmer (Khmer) Korean (한국어) Portuguese (português) Russian (Русский) Somali (af Soomaali) Spanish (español) Tagalog ( ... 정보 - 한국어 (Korean) PDF American Cancer Society Portuguese (português) Cancer Câncer - português (Portuguese) Bilingual PDF Health Information ...

  11. Vaginal cancer

    MedlinePlus

    Vaginal cancer; Cancer - vagina; Tumor - vaginal ... Most vaginal cancers occur when another cancer, such as cervical or endometrial cancer , spreads. This is called secondary vaginal cancer. Cancer ...

  12. Totally thorascopic surgical ablation of persistent AF and long-standing persistent atrial fibrillation using the "Dallas" lesion set.

    PubMed

    Edgerton, James R; Jackman, Warren M; Mahoney, Cecile; Mack, Michael J

    2009-12-01

    Minimally invasive surgery consisting of bipolar radiofrequency pulmonary vein (PV) isolation and limited ganglionated plexus ablation is effective in eliminating atrial fibrillation (AF) in patients with paroxysmal AF but is less effective in those with persistent AF or long-standing persistent AF. The purpose of this study was examine the results of minimally invasive surgery incorporating an additional set of radiofrequency ablation lines replicating a left-sided Cox maze III procedure. Thirty patients with persistent AF (n = 10) or long-standing persistent AF (n = 20) underwent minimally invasive surgery with an extended lesion set and PV isolation for a minimum follow-up of 6 months. Linear lesions were created at the roof line, at the anterior line, and between the roof line and the left atrial appendage. All patients underwent limited ganglionated plexus ablation and left atrial appendage excision as well as PV isolation verification. Block across the roof and anterior lines was confirmed in 29 (96.6%) of the 30 patients. Follow-up included 2-week event monitoring with auto-trigger in 21 patients, pacemaker interrogation in 8, and ECG in 1 who was in AF and refused longer-term monitoring. No operative mortality or major morbidity occurred. At 6 months, 24 (80%) of the 30 patients were free of AF: 15 (75%) with long-standing persistent AF and 9 (90%) with persistent AF. Among the six failures, burden of AF was low: one had 1 episode >15 seconds, two had 4 episodes, one had 6 episodes, one had >50 episodes, and one had AF on ECG and refused further monitoring. Early results of minimally invasive surgery with a new extended linear lesion set suggest increased efficacy over PV isolation and limited ganglionated plexus ablation in patients with persistent AF or long-standing persistent AF. PMID:19959146

  13. 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

  14. Anaerobic treatment of strong sewage by a two stage system of AF and UASB reactors.

    PubMed

    Sawajneh, Z; Al-Omari, A; Halalsheh, M

    2010-01-01

    An anaerobic treatment system that consists of an Anaerobic Filter (AF) and an Upflow Anaerobic Sludge Blanket (UASB) in series was built and operated to investigate its performance in treating strong domestic wastewater with high suspended solids fraction under Jordan's ambient temperatures of 25 degrees C for summer and 18 degrees C for winter. The system was operated from September 2003 until early April 2004. The system was operated at a Hydraulic Retention Time (HRT) of 4 hours for the first stage AF and 8 hours for the second stage UASB. Average COD(t) and COD(ss) removal efficiencies of the AF/UASB were 58% and 81% respectively for the operation period. The results showed that the first stage AF was effective in removing suspended solids. In addition, hydrolysis, acidification and methanogenesis took place in the first stage AF which was advantageous to the second stage UASB. It was concluded that the AF/UASB system is effective in treating strong domestic wastewater with high suspended solids content under Jordan's ambient temperatures. PMID:20418638

  15. PUF60: a novel U2AF65-related splicing activity.

    PubMed Central

    Page-McCaw, P S; Amonlirdviman, K; Sharp, P A

    1999-01-01

    We have identified a new pyrimidine-tract binding factor, PUF, that is required, together with U2AF, for efficient reconstitution of RNA splicing in vitro. The activity has been purified and consists of two proteins, PUF60 and the previously described splicing factor p54. p54 and PUF60 form a stable complex in vitro when cotranslated in a reaction mixture. PUF activity, in conjunction with U2AF, facilitates the association of U2 snRNP with the pre-mRNA. This reaction is dependent upon the presence of the large subunit of U2AF, U2AF65, but not the small subunit U2AF35. PUF60 is homologous to both U2AF65 and the yeast splicing factor Mud2p. The C-terminal domain of PUF60, the PUMP domain, is distantly related to the RNA-recognition motif domain, and is probably important in protein-protein interactions. PMID:10606266

  16. Oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system.

    PubMed

    Meng, Yao; Jost, Carsten; Mumme, Jan; Wang, Kaijun; Linke, Bernd

    2016-07-01

    In order to investigate the oxygen tolerance capacity of upflow anaerobic solid-state (UASS) with anaerobic filter (AF) system, the effect of microaeration on thermophilic anaerobic digestion of maize straw was investigated under batch conditions and in the UASS with AF system. Aeration intensities of 0-431mL O2/gvs were conducted as pretreatment under batch conditions. Aeration pretreatment obviously enhanced anaerobic digestion and an aeration intensity of 431mL O2/gvs increased the methane yield by 82.2%. Aeration intensities of 0-355mL O2/gvs were conducted in the process liquor circulation of the UASS with AF system. Dissolved oxygen (DO) of UASS and AF reactors kept around 1.39±0.27 and 0.99±0.38mg/L, respectively. pH was relatively stable around 7.11±0.04. Volatile fatty acids and soluble chemical oxygen demand concentration in UASS reactor were higher than those in AF reactor. Methane yield of the whole system was almost stable at 85±7mL/gvs as aeration intensity increased step by step. The UASS with AF system showed good oxygen tolerance capacity. PMID:27372134

  17. Detection of early bronchial cancer by autofluorescence: results in patients with H&N cancer

    NASA Astrophysics Data System (ADS)

    Gabrecht, Tanja; Radu, Alexandre; Zellweger, Matthieu; Lovisa, Blaise; Goujon, Didier; Grosjean, Pierre; van den Bergh, Hubert; Monnier, Philippe; Wagnières, Georges

    2007-07-01

    Head and neck (H&N) cancer patients have a high incidence of second primary tumours in the tracheobronchial tree. Diagnostic autofluorescence bronchoscopy (DAFE) has shown promising results in the detection of early neoplastic and pre-neoplastic changes in the bronchi. We have investigated the medical impact of DAFE in a population of H&N cancer patients. The bronchoscopies were performed using a modified commercially available DAFE system. Endoscopic imaging of the tissue autofluorescence (AF) was combined with an online image analysis procedure allowing to discriminate between true and false positive results. White light (WL) bronchoscopy was performed as a control. Twenty-one patients with high lung cancer risk factors underwent WL and AF bronchoscopy with this improved system. Forty-one biopsies were taken on macroscopicall suspicious (WL or AF positive) sites. Seven patients were found to have second primary tumours in the bronchi. The sensitivity for the detection of these early lesions with the DAFE was 1.6 times larger than the sensitivity of WL bronchoscopy only. The positive predictive value (PPV) for AF is 79% (33% for WL alone). The PPV of both methods together is 100%. DAFE proved to be efficient for the detection of second primary lesions in H&N cancer patients and can be used as a simple addition to pre-operative work-up or follow-up in this patient population.

  18. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia.

    PubMed

    Sanjuan-Pla, Alejandra; Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W; Marschalek, Rolf; Menéndez, Pablo

    2015-12-17

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a "multiple-and-sequential-hit" model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one "big-hit" might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  19. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    PubMed Central

    Bueno, Clara; Prieto, Cristina; Acha, Pamela; Stam, Ronald W.; Marschalek, Rolf; Menéndez, Pablo

    2015-01-01

    Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinical management and survival (∼85-90%) of childhood B-ALL, the outcome of infants with MLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infant B-ALL, t(4;11)+ patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiveness and short latency, current progress on its etiology, pathogenesis, and cellular origin is limited as evidenced by the lack of mouse/human models recapitulating the disease phenotype/latency. We propose this is because infant cancer is from an etiologic and pathogenesis standpoint distinct from adult cancer and should be seen as a developmental disease. This is supported by whole-genome sequencing studies suggesting that opposite to the view of cancer as a “multiple-and-sequential-hit” model, t(4;11) alone might be sufficient to spawn leukemia. The stable genome of these patients suggests that, in infant developmental cancer, one “big-hit” might be sufficient for overt disease and supports a key contribution of epigenetics and a prenatal cell of origin during a critical developmental window of stem cell vulnerability in the leukemia pathogenesis. Here, we revisit the biology of t(4;11)+ infant B-ALL with an emphasis on its origin, genetics, and disease models. PMID:26463423

  20. AF9 promotes hESC neural differentiation through recruiting TET2 to neurodevelopmental gene loci for methylcytosine hydroxylation

    PubMed Central

    Qiao, Yunbo; Wang, Xiongjun; Wang, Ran; Li, Yuanyuan; Yu, Fang; Yang, Xianfa; Song, Lu; Xu, Guoliang; Chin, Y Eugene; Jing, Naihe

    2015-01-01

    AF9 mutations have been implicated in human neurodevelopmental diseases and murine Af9 mediates histone methylation during cortical neuron generation. However, AF9 function and related mechanisms in human neurodevelopment remain unknown. Here we show that AF9 is necessary and sufficient for human embryonic stem cell (hESC) neural differentiation and neurodevelopmental gene activation. The 5-methylcytosine (5mC) dioxygenase TET2, which was identified in an AF9-associated protein complex, physically interacted with AF9. Both AF9 and TET2 co-localized in 5-hydroxymethylcytosine (5hmC)-positive hESC-derived neurons and were required for appropriate hESC neural differentiation. Upon binding to AAC-containing motifs, AF9 recruited TET2 to occupy the common neurodevelopmental gene loci to direct 5mC-to-5hmC conversion, which was followed by sequential activation of neural target genes and hESC neural commitment. These findings define an AF9–TET2 regulatory complex for modulating human neural development and reveal a novel mechanism by which the AF9 recognition specificity and TET2 hydroxylation activity cooperate to control neurodevelopmental gene activation. PMID:27462416

  1. Statin Therapy for the Prevention of Atrial Fibrillation Trial (SToP AF trial)

    PubMed Central

    Negi, Smita; Shukrullah, Irfan; Veledar, Emir; Bloom, Heather L.; Jones, Dean P.; Dudley, Samuel C.

    2010-01-01

    Background Inflammation and oxidative stress are associated with atrial fibrillation (AF). Statins have antioxidant and anti-inflammatory properties. We tested if atorvastatin reduced AF recurrence after DC cardioversion (CV) by modifying systemic oxidative stress and inflammation. (NCT00252967) Methods and Results In a randomized, double-blinded, placebo-controlled trial, patients with atrial fibrillation/flutter (AF) were randomized to receive either atorvastatin 80 mg (n=33) or placebo (n=31) before CV. Treatment was continued for 12 months or until AF recurred. Serum oxidative stress markers (ratios of oxidized to reduced glutathione and cysteine, derivatives of reactive oxygen species, isoprostanes) and inflammatory markers [ high sensitivity C- reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α (TNFα)] were measured at baseline and on follow-up. AF recurred in 22 (66.7%) of atorvastatin and 26 (83.9%) of placebo group (p=0.2). The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 (95% CI: 0.98-1.01, p=0.3). There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates (median (IR): 29 (2-145) days vs. 22 (7-70) days, p=0.9). While no significant effect was seen on oxidative stress, 2 of 4 inflammatory markers, IL-6 (adjusted OR: 0.59, 95% CI: 0.35-0.97, p= 0.04) and hs-CRP (adjusted OR: 0.59, 95% CI: 0.37-0.95, p=0.03) were significantly lowered with atorvastatin. Cholesterol levels significantly decreased with atorvastatin (p=0.03). Conclusions High dose atorvastatin did not reduce the recurrence of AF after CV. It reduced selective markers of inflammation without affecting systemic oxidative stress. Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress. PMID:20946227

  2. Natalizumab-induced POU2AF1/Spi-B upregulation

    PubMed Central

    Meira, Maria; Sievers, Claudia; Hoffmann, Francine; Haghikia, Aiden; Rasenack, Maria; Décard, Bernhard F.; Kuhle, Jens; Derfuss, Tobias; Kappos, Ludwig

    2016-01-01

    Objectives: To assess messenger RNA (mRNA) expression of POU2AF1 and Spi-B and their potential regulatory microRNAs (miRNAs) in natalizumab-treated patients with multiple sclerosis and in therapy-associated progressive multifocal leukoencephalopathy (PML). Methods: Expression of POU2AF1/Spi-B was analyzed by using real-time reverse transcription PCR assays on isolated B/CD8+ T lymphocytes and peripheral blood mononuclear cells (PBMCs) from cohorts of untreated and natalizumab-treated patients with and without PML. Longitudinal expression analysis was performed on CD4+, CD8+ T and B cells from 14 patients who interrupted natalizumab therapy for 8 weeks. The miRNA profiling was conducted in PBMCs from 5 untreated and 5 natalizumab-treated patients using low-density arrays followed by validation with single miRNAs assays in untreated and natalizumab-treated patients. Results: POU2AF1 and Spi-B mRNAs were upregulated in B and CD8+ T cells from natalizumab-treated patients, which was validated in PBMCs from different cohorts of natalizumab-treated patients with and without PML, with a noteworthy higher expression of Spi-B in patients with PML. In contrast, downregulation of POU2AF1/Spi-B expression was measured in B and CD8+ T cells after natalizumab discontinuation. Seventeen differentially expressed miRNAs including miR-10b, a regulator of POU2AF1 mRNA, were identified in long-term natalizumab-treated patients compared with untreated ones. Conclusions: Upregulation of POU2AF1 and Spi-B, known transactivators of the JC virus, the causative agent for PML, and its association with occurrence of PML in natalizumab-treated patients, corroborates POU2AF1/Spi-B as potential biomarkers for PML risk, which merits further evaluation. PMID:27088119

  3. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    SciTech Connect

    Thakker, A.B.; Cowles, B.A.

    1983-04-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  4. A simple web-based tool to compare freshwater fish data collected using AFS standard methods

    USGS Publications Warehouse

    Bonar, Scott A.; Mercado-Silva, Norman; Rahr, Matt; Torrey, Yuta T.; Cate, Averill, Jr.

    2016-01-01

    The American Fisheries Society (AFS) recently published Standard Methods for Sampling North American Freshwater Fishes. Enlisting the expertise of 284 scientists from 107 organizations throughout Canada, Mexico, and the United States, this text was developed to facilitate comparisons of fish data across regions or time. Here we describe a user-friendly web tool that automates among-sample comparisons in individual fish condition, population length-frequency distributions, and catch per unit effort (CPUE) data collected using AFS standard methods. Currently, the web tool (1) provides instantaneous summaries of almost 4,000 data sets of condition, length frequency, and CPUE of common freshwater fishes collected using standard gears in 43 states and provinces; (2) is easily appended with new standardized field data to update subsequent queries and summaries; (3) compares fish data from a particular water body with continent, ecoregion, and state data summaries; and (4) provides additional information about AFS standard fish sampling including benefits, ongoing validation studies, and opportunities to comment on specific methods. The web tool—programmed in a PHP-based Drupal framework—was supported by several AFS Sections, agencies, and universities and is freely available from the AFS website and fisheriesstandardsampling.org. With widespread use, the online tool could become an important resource for fisheries biologists.

  5. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    PubMed

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development. PMID:24551202

  6. Low strain, long life creep fatigue of AF2-1DA and INCO 718

    NASA Technical Reports Server (NTRS)

    Thakker, A. B.; Cowles, B. A.

    1983-01-01

    Two aircraft turbine disk alloys, GATORIZED AF2-DA and INCO 718 were evaluated for their low strain long life creep-fatigue behavior. Static (tensile and creep rupture) and cyclic properties of both alloys were characterized. The cntrolled strain LCF tests were conducted at 760 C (1400 F) and 649 C (1200 F) for AF2-1DA and INCO 718, respectively. Hold times were varied for tensile, compressive and tensile/compressive strain dwell (relaxation) tests. Stress (creep) hold behavior of AF2-1DA was also evaluated. Generally, INCO 718 exhibited more pronounced reduction in cyclic life due to hold than AF2-1DA. The percent reduction in life for both alloys for strain dwell tests was greater at low strain ranges (longer life regime). Changing hold time from 0 to 0.5, 2.0 and 15.0 min. resulted in corresponding reductions in life. The continuous cycle and cyclic/dwell initiation failure mechanism was predominantly transgranular for AF2-1DA and intergranular for INCO 718.

  7. Effect of X irradiation on optical properties of Teflon-AF

    NASA Astrophysics Data System (ADS)

    Jahan, M. S.; Ermer, D. R.; Cooke, D. W.

    1993-03-01

    Radiation effects in optical-grade amorphous fluoropolymer, Teflon-AF, is investigated by UV-visible absorption and electron spin resonance (ESR) measurements. When irradiated with low-energy (40 kVp) X-rays at room temperature in air, Teflon-AF is found to develop a broad, structureless UV-absorption band in the wavelength interval 200-350 nm. While the UV absorption increases as a function of X-ray dose, with relative rates of approx 2 × 10 -5 Gy -1 (1 × 10 -5 Gy -1) in Teflon-AF 1600 (Teflon-AF 2400), its optical transparency for a given dose of 67.5 kGy, however, remains unaffected. Additional measurements conducted using electron spin resonance (ESR) technique reveal that the observed UV absorption is caused by the X-ray induced peroxy radical (POO .˙). The results also suggest that the inclusion of dioxole monomer in the PTFE chain not only improves the optical clarity of Teflon-AF, as reported, but also increases its radiation tolerance. During a post-irradiation storage in air at RT for about 30 days the peroxy radical is observed to decay, with a concomitant decrease in UV absorption. A tentative model is proposed to explain the radiation damage and recovery mechanisms.

  8. Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction

    PubMed Central

    Washington, Erica J.; Mukhtar, M. Shahid; Finkel, Omri M.; Wan, Li; Kieber, Joseph J.; Dangl, Jeffery L.

    2016-01-01

    HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis. We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site-specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID:27274076

  9. A Critical Role for CRM1 in Regulating HOXA Gene Transcription in CALM-AF10 Leukemias

    PubMed Central

    Conway, Amanda E.; Haldeman, Jonathan M.; Wechsler, Daniel S.; Lavau, Catherine P.

    2014-01-01

    The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor. PMID:25027513

  10. An Evaluation of the Impacts of AF-M315E Propulsion Systems for Varied Mission Applications

    NASA Technical Reports Server (NTRS)

    Deans, Matthew C.; Oleson, Steven R.; Fittje, James; Colozza, Anthony; Packard, Tom; Gyekenyesi, John; McLean, Christopher H.; Spores, Ronald A.

    2015-01-01

    The purpose of the AF-M315E COMPASS study is to identify near-term (3-5 years) and long term (5 years +) opportunities for infusion, specifically the thruster and associated component technologies being developed as part of the GPIM project. Develop design reference missions which show the advantages of the AF-M315E green propulsion system. Utilize a combination of past COMPASS designs and selected new designs to demonstrate AF-M315E advantages. Use the COMPASS process to show the puts and takes of using AF-M315E at the integrated system level.

  11. Outcomes registry for better informed treatment of atrial fibrillation II: Rationale and design of the ORBIT-AF II registry

    PubMed Central

    Steinberg, Benjamin A.; Blanco, Rosalia G.; Ollis, Donna; Kim, Sunghee; Holmes, DaJuanicia N.; Kowey, Peter R.; Fonarow, Gregg C.; Ansell, Jack; Gersh, Bernard; Go, Alan S.; Hylek, Elaine; Mahaffey, Kenneth W.; Thomas, Laine; Chang, Paul; Peterson, Eric D.; Piccini, Jonathan P.

    2014-01-01

    Background Recent clinical trials have demonstrated the safety and efficacy of several non–vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF). However, there are limited data on their use and outcomes in routine clinical practice, particularly among patients newly diagnosed as having AF and patients with AF recently transitioned to a NOAC. Methods/Design ORBIT-AF II is a multicenter, national registry of patients with AF that is enrolling up to 15,000 newly diagnosed patients with AF and/or those with AF recently transitioned to a NOAC from 300 US outpatient practices. These patients will be followed for up to 2 years, including clinical status, outcomes (major adverse cardiovascular events, bleeding), and management of anticoagulation surrounding bleeding events. In addition, detailed data regarding the use of these agents in and around cardiac procedures, their complications, and management of such complications will be collected. Conclusions The ORBIT-AF II registry will provide valuable insights into the safety and effectiveness of NOACs used in AF in community practice settings. PMID:25066554

  12. SIP1/NHERF2 enhances estrogen receptor alpha transactivation in breast cancer cells

    PubMed Central

    Meneses-Morales, Ivan; Tecalco-Cruz, Angeles C.; Barrios-García, Tonatiuh; Gómez-Romero, Vania; Trujillo-González, Isis; Reyes-Carmona, Sandra; García-Zepeda, Eduardo; Méndez-Enríquez, Erika; Cervantes-Roldán, Rafael; Pérez-Sánchez, Víctor; Recillas-Targa, Félix; Mohar-Betancourt, Alejandro; León-Del-Río, Alfonso

    2014-01-01

    The estrogen receptor alpha (ERα) is a ligand-activated transcription factor that possesses two activating domains designated AF-1 and AF-2 that mediate its transcriptional activity. The role of AF-2 is to recruit coregulator protein complexes capable of modifying chromatin condensation status. In contrast, the mechanism responsible for the ligand-independent AF-1 activity and for its synergistic functional interaction with AF-2 is unclear. In this study, we have identified the protein Na+/H+ Exchanger RegulatoryFactor 2 (NHERF2) as an ERα-associated coactivator that interacts predominantly with the AF-1 domain of the nuclear receptor. Overexpression of NHERF2 in breast cancer MCF7 cells produced an increase in ERα transactivation. Interestingly, the presence of SRC-1 in NHERF2 stably overexpressing MCF7 cells produced a synergistic increase in ERα activity. We show further that NHERF2 interacts with ERα and SRC-1 in the promoter region of ERα target genes. The binding of NHERF2 to ERα in MCF7 cells increased cell proliferation and the ability of MCF7 cells to form tumors in a mouse model. We analyzed the expression of NHERF2 in breast cancer tumors finding a 2- to 17-fold increase in its mRNA levels in 50% of the tumor samples compared to normal breast tissue. These results indicate that NHERF2 is a coactivator of ERα that may participate in the development of estrogen-dependent breast cancer tumors. PMID:24771346

  13. Design and position control of AF lens actuator for mobile phone using IPMC-EMIM

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Joo; Kim, Chul-Jin; Park, No-Cheol; Yang, Hyun-Seok; Park, Young-Pil; Park, Kang-Ho; Lee, Hyung-Kun; Choi, Nak-Jin

    2008-03-01

    IPMC-EMIM (Ionic Polyer Metal Composites + 1-ethyl-3- methyl imidazolium trifluromethane sulfonate, EMIM-Tfo) is fabricated by substituting ionic liquid for water in Nafion film, which improves water sensitiveness of IPMC and guarantees uniform performance regardless of the surrounding environment. In this paper, we will briefly introduce the procedure of fabrication of IPMC-EMIM and proceed to introduce the Hook-type actuator using IPMC-EMIM and application to AF Lens actuator. Parameters of Hook-type actuator are estimated from experimental data. In the simulation, The proposed AF Lens Actuator is assumed to be a linear system and based on estimated parameters, PID controller will be designed and controlled motion of AF Lens actuator will be shown through simulation.

  14. Cloning and characterization of two duplicated interleukin-17A/F2 genes in common carp (Cyprinus carpio L.): Transcripts expression and bioactivity of recombinant IL-17A/F2.

    PubMed

    Li, Hongxia; Yu, Juhua; Li, Jianlin; Tang, Yongkai; Yu, Fan; Zhou, Jie; Yu, Wenjuan

    2016-04-01

    Interleukin-17 (IL-17) plays an important role in inflammation and host defense in mammals. In this study, we identified two duplicated IL-17A/F2 genes in the common carp (Cyprinus carpio) (ccIL-17A/F2a and ccIL-17A/F2b), putative encoded proteins contain 140 amino acids (aa) with conserved IL-17 family motifs. Expression analysis revealed high constitutive expression of ccIL-17A/F2s in mucosal tissues, including gill, skin and intestine, their expression could be induced by Aeromonas hydrophila, suggesting a potential role in mucosal immunity. Recombinant ccIL-17A/F2a protein (rccIL-17A/F2a) produced in Escherichia coli could induce the expression of proinflammatory cytokines (IL-1β) and the antimicrobial peptides S100A1, S100A10a and S100A10b in the primary kidney in a dose- and time-dependent manner. Above findings suggest that ccIL-17A/F2 plays an important role in both proinflammatory and innate immunity. Two duplicated ccIL-17A/F2s showed different expression level with ccIL-17A/F2a higher than b, comparison of two 5' regulatory regions indicated the length from anticipated promoter to transcriptional start site (TSS) and putative transcription factor binding site (TFBS) were different. Promoter activity of ccIL-17A/F2a was 2.5 times of ccIL-17A/F2b which consistent with expression results of two genes. These suggest mutations in 5'regulatory region contributed to the differentiation of duplicated genes. To our knowledge, this is the first report to analyze 5'regulatory region of piscine IL-17 family genes. PMID:26921542

  15. Compliance testing of the Clear AFS Power Plant, coal-fired boiler 1, Clear AFS, Alaska. Final report, 18-23 April 1989

    SciTech Connect

    Scott, P.T.

    1989-10-01

    The 13 MWS/DE through HQ AFSPACECOM/SG requested AFOEHL Quality Function conduct source emission testing of the Clear AFS Power Plant to determine compliance with applicable Alaska Air Quality Control Codes. The Alaska Department of Environmental Conservation required testing of one representative boiler for permit compliance and to determine operating limitations for each boiler. At 80,000 lbs steam/hour particulate emission were within emission limits allowed by the State of Alaska.

  16. 27. "SITE PLAN." Specifications No. OC15775, Drawing No. AF600915, sheet ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    27. "SITE PLAN." Specifications No. OC1-57-75, Drawing No. AF-60-09-15, sheet 1 of 96, D.O. Series No. AF 1394/20, Rev. B. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract no. 5296 Rev. B, Date: 11/17/59. Site plan of 20,000-foot track, including construction phasing notes. - Edwards Air Force Base, South Base Sled Track, Edwards Air Force Base, North of Avenue B, between 100th & 140th Streets East, Lancaster, Los Angeles County, CA

  17. Multi-object spectroscopy data reduction: the AF2+WYFFOS pipeline

    NASA Astrophysics Data System (ADS)

    Domínquez Palmero, Lilian; Jackson, Richard; Molaeinezhad, Alireza; Fariña, Cecilia; Balcells, Marc; Benn, Chris R.

    2014-08-01

    The scientific productivity of complex instrumentation strongly depends on the availability of data-reduction pipelines. In the case of AF2+WYFFOS, the multi-object one-degree field-of-view fibre-fed spectrograph at the 4.2 m William Herschel Telescope (WHT), the full scientific exploitation of the data has often been slowed down because of the non-availability of a pipeline. A dedicated pipeline has been developed to overcome this. Running in IDL, it performs full reduction of AF2+WYFFOS data: fibre-to-fibre sensitivity corrections, fibre tracing, wavelength calibration, optimal extraction, sky subtraction.

  18. Modeling spall in HY100, HY130, and AF1410 steels

    NASA Astrophysics Data System (ADS)

    Garrett, R. K.; Rajendran, A. M.; Last, H. R.

    1996-05-01

    A comparison spall analysis between three matensitic steels: HY100, HY130, and AF1410 is presented Metallurgical observations on the fracture surfaces of uniaxial tensile specimens as well as the spalled target plates confirmed the nucleation, growth, and coalescence of microvoids in these steels. The threshold stress for void nucleation in these steels were determined from the spall analysis using the EPIC finite element code. According to the model, the spall nucleation occurred at higher stress levels in AF1410 compared to HY100 and HY130. A complete set of material model constants has been determined for these three steels.

  19. A CALM-derived nuclear export signal is essential for CALM-AF10–mediated leukemogenesis

    PubMed Central

    Conway, Amanda E.; Scotland, Paula B.; Lavau, Catherine P.

    2013-01-01

    The t(10;11) chromosomal translocation gives rise to the CALM-AF10 fusion gene and is found in patients with aggressive and difficult-to-treat hematopoietic malignancies. CALM-AF10–driven leukemias are characterized by HOXA gene up-regulation and a global reduction in H3K79 methylation. DOT1L, the H3K79 methyltransferase, interacts with the octapeptide/leucine zipper domain of AF10, and this region has been shown to be necessary and sufficient for CALM-AF10–mediated transformation. However, the precise role of CALM in leukemogenesis remains unclear. Here, we show that CALM contains a nuclear export signal (NES) that mediates cytoplasmic localization of CALM-AF10 and is necessary for CALM-AF10–dependent transformation. Fusions of the CALM NES (NESCALM-AF10) or NES motifs from heterologous proteins (ABL1, Rev, PKIA, APC) in-frame with AF10 are sufficient to immortalize murine hematopoietic progenitors in vitro. The CALM NES is essential for CALM-AF10–dependent Hoxa gene up-regulation and aberrant H3K79 methylation, possibly by mislocalization of DOT1L. Finally, we observed that CALM-AF10 leukemia cells are selectively sensitive to inhibition of nuclear export by Leptomycin B. These findings uncover a novel mechanism of leukemogenesis mediated by the nuclear export pathway and support further investigation of the utility of nuclear export inhibitors as therapeutic agents for patients with CALM-AF10 leukemias. PMID:23487024

  20. The splicing factor U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis

    SciTech Connect

    Kim, Jeonghee; Chung, In Kwon

    2014-01-17

    Highlights: •Identification of U2AF65 as a novel TRF1-interacting protein. •U2AF65 stabilizes TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. •U2AF65 interferes with the interaction between TRF1 and Fbx4. •U2AF65 represents a new route for modulating TRF1 function at telomeres. -- Abstract: The human telomeric protein TRF1 is a component of the six-subunit protein complex shelterin, which provides telomere protection by organizing the telomere into a high-order structure. TRF1 functions as a negative regulator of telomere length by controlling the access of telomerase to telomeres. Thus, the cellular abundance of TRF1 at telomeres should be maintained and tightly regulated to ensure proper telomere function. Here, we identify U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 (U2AF65), an essential pre-mRNA splicing factor, as a novel TRF1-interacting protein. U2AF65 interacts with TRF1 in vitro and in vivo and is capable of stabilizing TRF1 protein by inhibiting its ubiquitin-dependent proteolysis. We also found that U2AF65 interferes with the interaction between TRF1 and Fbx4, an E3 ubiquitin ligase for TRF1. Depletion of endogenous U2AF65 expression by short interfering RNA (siRNA) reduced the stability of endogenous TRF1 whereas overexpression of U2AF65 significantly extended the half-life of TRF1. These findings demonstrate that U2AF65 plays a critical role in regulating the level of TRF1 through physical interaction and ubiquitin-mediated proteolysis. Hence, U2AF65 represents a new route for modulating TRF1 function at telomeres.

  1. Studies on electrochemical oxidation of estrogenic disrupting compound bisphenol AF and its interaction with human serum albumin.

    PubMed

    Wang, Xin; Yang, Jichun; Wang, Yuejiao; Li, Yanhui; Wang, Fang; Zhang, Lei

    2014-07-15

    Bisphenol AF (BPAF) is an environmental pollutant to disrupt endocrine system or cause cancer, thus the detection of trace BPAF is very important. In this study, a simple and highly sensitive electroanalytical method for the determination of BPAF was developed. In pH 6.0 phosphate buffer solutions, carboxyl functionalized multi-walled carbon nanotubes (MWCNT-COOH) modified glassy carbon electrode exhibits an enhanced effectiveness for the oxidation of BPAF. This electrode exhibited two linear relationships with BPAF concentration range of 0.02μmolL(-1) to 8.0μmolL(-1) and a detection limit of 0.0077μmolL(-1) (S/N=3). The proposed method was successfully applied to determine BPAF in real samples and the results were satisfactory. The MWCNT-COOH/GCE electrode showed good reproducibility, stability and anti-interference. The electrochemistry and spectroscopy methods are also described for the evaluation of BPAF-HSA interaction. In the presence of HSA, the peak currents of BPAF decreased linearly due to the formation of a super-molecular complex. The binding constant between BPAF and HSA, obtained by differential pulse voltammetry (DPV), was consistent with the fluorescence analysis. The molecular modeling studies were carried out to clearly describe the interaction between BPAF and HSA. PMID:24866560

  2. 77 FR 14287 - Aspergillus flavus AF36; Amendment to an Exemption From the Requirement of a Tolerance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-09

    ...This regulation amends the existing temporary tolerance exemption for Aspergillus flavus AF36 by establishing a permanent exemption from the requirement of a tolerance for residues of the microbial pesticide, Aspergillus flavus AF36, in or on pistachio when applied as an antifungal agent and used in accordance with good agricultural practices. On behalf of the Arizona Cotton Research and......

  3. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea.

    PubMed

    Dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues; Goldman, Gustavo H; Riaño-Pachón, Diego M

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  4. Identification and Characterization of an Antifungal Protein, AfAFPR9, Produced by Marine-Derived Aspergillus fumigatus R9.

    PubMed

    Rao, Qi; Guo, Wenbin; Chen, Xinhua

    2015-05-01

    A fungal strain, R9, was isolated from the South Atlantic sediment sample and identified as Aspergillus fumigatus. An antifungal protein, AfAFPR9, was purified from the culture supernatant of Aspergillus fumigatus R9. AfAFPR9 was identified to be restrictocin, which is a member of the ribosome-inactivating proteins (RIPs), by MALDI-TOF-TOF-MS. AfAFPR9 displayed antifungal activity against plant pathogenic Fusarium oxysporum, Alternaria longipes, Colletotrichum gloeosporioides, Paecilomyces variotii, and Trichoderma viride at minimum inhibitory concentrations of 0.6, 0.6, 1.2, 1.2, and 2.4 μg/disc, respectively. Moreover, AfAFPR9 exhibited a certain extent of thermostability, and metal ion and denaturant tolerance. The iodoacetamide assay showed that the disulfide bridge in AfAFPR9 was indispensable for its antifungal action. The cDNA encoding for AfAFPR9 was cloned from A. fumigatus R9 by RTPCR and heterologously expressed in E. coli. The recombinant AfAFPR9 protein exhibited obvious antifungal activity against C. gloeosporioides, T. viride, and A. longipes. These results reveal the antifungal properties of a RIP member (AfAFPR9) from marine-derived Aspergillus fumigatus and indicated its potential application in controlling plant pathogenic fungi. PMID:25394604

  5. Draft Genome Sequence of Komagataeibacter intermedius Strain AF2, a Producer of Cellulose, Isolated from Kombucha Tea

    PubMed Central

    dos Santos, Renato Augusto Corrêa; Berretta, Andresa Aparecida; Barud, Hernane da Silva; Ribeiro, Sidney José Lima; González-García, Laura Natalia; Zucchi, Tiago Domingues

    2015-01-01

    Here, we present the draft genome sequence of Komagataeibacter intermedius strain AF2, which was isolated from Kombucha tea and is capable of producing cellulose, although at lower levels compared to another bacterium from the same environment, K. rhaeticus strain AF1. PMID:26634755

  6. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  7. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  8. 40 CFR 180.1206 - Aspergillus flavus AF36; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... tolerance is established for residues of Aspergillus flavus AF36 in or on corn, field, forage; corn, field, grain; corn, field, stover; corn, field, aspirated grain fractions; corn, sweet, kernel plus cob with husk removed; corn, sweet, forage; corn, sweet, stover; corn, pop, grain; and corn, pop, stover,...

  9. Fracture Mechanics Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, J. W.; Martinez, J.; McLean, C.

    2016-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant on orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent processing flaws will not cause failure during the design life of the tank. Material property inputs for this analysis require testing to determine the stress intensity factor for environment-assisted cracking (KEAC) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched, or SE(B), specimens representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to AF-M315E at 50 C for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor for environment-assisted cracking of the Ti 6Al-4V forged tank material was found to be at least 22 ksivin and at least 31 ksivin for the weld material when exposed to AF-M315E monopropellant.

  10. K-theory of the chair tiling via AF-algebras

    NASA Astrophysics Data System (ADS)

    Julien, Antoine; Savinien, Jean

    2016-08-01

    We compute the K-theory groups of the groupoid C∗-algebra of the chair tiling, using a new method. We use exact sequences of Putnam to compute these groups from the K-theory groups of the AF-algebras of the substitution and the induced lower dimensional substitutions on edges and vertices.

  11. 28. Site Plan: AF Station P67, Fort Custer, Michigan, Plot ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. Site Plan: AF Station P-67, Fort Custer, Michigan, Plot Plan (to accompany FY 1956 project planning report), USACOE, 22 July 1954. - Fort Custer Military Reservation, P-67 Radar Station, .25 mile north of Dickman Road, east of Clark Road, Battle Creek, Calhoun County, MI

  12. Acutangulosides A-F, monodesmosidic saponins from the bark of Barringtonia acutangula.

    PubMed

    Mills, Clive; Carroll, Anthony R; Quinn, Ronald J

    2005-03-01

    Nine triterpene saponins, acutangulosides A-F (2-7), and acutanguloside D-F methyl esters (5a-7a) and a single triterpene aglycone (1) were isolated from a water extract of the bark of Barringtonia acutangula. Their structures were assigned on the basis of spectroscopic data. PMID:15787427

  13. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.

    PubMed

    Zhou, Haixia; Brekman, Angelika; Zuo, Wu-Lin; Ou, Xuemei; Shaykhiev, Renat; Agosto-Perez, Francisco J; Wang, Rui; Walters, Matthew S; Salit, Jacqueline; Strulovici-Barel, Yael; Staudt, Michelle R; Kaner, Robert J; Mezey, Jason G; Crystal, Ronald G; Wang, Guoqing

    2016-04-01

    In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU domain class 2-associating factor 1 (POU2AF1), a known transcription cofactor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of upregulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation, and analysis of differentiating single basal cell clones. Lentivirus-mediated upregulation of POU2AF1 in airway basal cells induced upregulation of host defense genes, including MX1, IFIT3, IFITM, and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, and BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a host defense tone even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium. PMID:26927796

  14. Bisphenol AF Is a Full Agonist for the Estrogen Receptor ERα but a Highly Specific Antagonist for ERβ

    PubMed Central

    Matsushima, Ayami; Liu, Xiaohui; Okada, Hiroyuki; Shimohigashi, Miki; Shimohigashi, Yasuyuki

    2010-01-01

    Background Bisphenol AF has been acknowledged to be useful for the production of CF3-containing polymers with improved chemical, thermal, and mechanical properties. Because of the lack of adequate toxicity data, bisphenol AF has been nominated for comprehensive toxicological characterization. Objectives We aimed to determine the relative preference of bisphenol AF for the human nuclear estrogenic receptors ERα and ERβ and the bisphenol A–specific estrogen-related receptor ERRγ, and to clarify structural characteristics of receptors that influence bisphenol AF binding. Methods We examined receptor-binding activities of bisphenol AF relative to [3H]17β-estradiol (for ERα and ERβ) and [3H]bisphenol A (for ERRγ). Functional luciferase reporter gene assays were performed to assess receptor activation in HeLa cells. Results We found that bisphenol AF strongly and selectively binds to ERs over ERRγ. Furthermore, bisphenol AF receptor-binding activity was three times stronger for ERβ [IC50 (median inhibitory concentration) = 18.9 nM] than for ERα. When examined using a reporter gene assay, bisphenol AF was a full agonist for ERα. In contrast, it was almost completely inactive in stimulating the basal constitutive activity of ERβ. Surprisingly, bisphenol AF acted as a distinct and strong antagonist against the activity of the endogenous ERβ agonist 17β-estradiol. Conclusion Our results suggest that bisphenol AF could function as an endocrine-disrupting chemical by acting as an agonist or antagonist to perturb physiological processes mediated through ERα and/or ERβ. PMID:20427257

  15. TYPE AF CERTIFICATE FOR TRANSPORTATION OF LOW ENRICHED URANIUM OXIDE (LEUO) FOR DISPOSAL

    SciTech Connect

    Opperman, E; Kenneth Yates, K

    2007-10-19

    Washington Savannah River Company (WSRC) operates the Savannah River Site (SRS) in Aiken, SC under contract with the U.S. Department of Energy (DOE). SRS had the need to ship 227 drums of low enriched uranium oxide (LEUO) to a disposal site. The LEUO had been packaged nearly 25 years ago in U.S. Department of Transportation (DOT) 17C 55-gallon drums and stored in a warehouse. Since the 235U enrichment was just above 1 percent by weight (wt%) the material did not qualify for the fissile material exceptions in 49 CFR 173.453, and therefore was categorized as 'fissile material' for shipping purposes. WSRC evaluated all existing Type AF packages and did not identify any feasible packaging. Applying for a new Type AF certificate of compliance was considered too costly for a one-time/one-way shipment for disposal. Down-blending the material with depleted uranium (to reduce enrichment below 1 wt% and enable shipment as low specific activity (LSA) radioactive material) was considered, but appropriate blending facilities do not exist at SRS. After reviewing all options, WSRC concluded that seeking a DOT Special Permit was the best option to enable shipment of the material for permanent disposal. WSRC submitted the Special Permit application to the DOT, and after one request-for-additional-information (RAI) the permit was considered acceptable. However, in an interesting development that resulted from the DOT Special Permit application process, it was determined that it was more appropriate for the DOE to issue a Type AF certificate [Ref. 1] for this shipping campaign. This paper will outline the DOT Special Permit application and Type AF considerations, and will discuss the issuance of the new DOE Type AF certificate of compliance.

  16. Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4-MLL Fusion Protein.

    PubMed

    Sabiani, Samaneh; Geppert, Tim; Engelbrecht, Christian; Kowarz, Eric; Schneider, Gisbert; Marschalek, Rolf

    2015-05-01

    We have recently demonstrated that Taspase1-mediated cleavage of the AF4-MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4-MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4-MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4-MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4-MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID:26137584

  17. Eye Cancer

    MedlinePlus

    ... Eye Cancer - Overview Request Permissions Print to PDF Eye Cancer - Overview Approved by the Cancer.Net Editorial Board , ... Cancer Research and Advocacy Survivorship Blog About Us Eye Cancer Guide Cancer.Net Guide Eye Cancer Overview Statistics ...

  18. Cancer - resources

    MedlinePlus

    Resources - cancer ... The following organizations are good resources for information on cancer : American Cancer Society -- www.cancer.org Cancer Care -- www.cancercare.org National Cancer Institute -- www.cancer.gov

  19. Steroid hormone receptors and prostate cancer: role of structural dynamics in therapeutic targeting.

    PubMed

    Kumar, Raj

    2016-01-01

    Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time. Therefore, to maximize the efficacy of SHR-based therapeutics, the possibility of developing unique modulators that act to control AF1 activity must be considered. Recent studies targeting androgen receptor's (AR's) ID AF1 domain for the castration-resistant prostate cancer has provided the possibility of therapeutically targeting ID NTD/AF1 surfaces by allosteric modulations to achieve desired effects. In this review article, we discuss how inter- and intra- molecular allosteric regulations controlled by AR's structural flexibility and dynamics particularly the ID NTD/AF1 is an emerging area of investigation, which could be exploited for drug development and therapeutic targeting of prostate cancer. PMID:27364545

  20. Steroid hormone receptors and prostate cancer: role of structural dynamics in therapeutic targeting

    PubMed Central

    Kumar, Raj

    2016-01-01

    Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time. Therefore, to maximize the efficacy of SHR-based therapeutics, the possibility of developing unique modulators that act to control AF1 activity must be considered. Recent studies targeting androgen receptor's (AR's) ID AF1 domain for the castration-resistant prostate cancer has provided the possibility of therapeutically targeting ID NTD/AF1 surfaces by allosteric modulations to achieve desired effects. In this review article, we discuss how inter- and intra- molecular allosteric regulations controlled by AR's structural flexibility and dynamics particularly the ID NTD/AF1 is an emerging area of investigation, which could be exploited for drug development and therapeutic targeting of prostate cancer. PMID:27364545

  1. Binding of hnRNP H and U2AF65 to Respective G-codes and a Poly-Uridine Tract Collaborate in the N50-5'ss Selection of the REST N Exon in H69 Cells

    PubMed Central

    Ortuño-Pineda, Carlos; Galindo-Rosales, José Manuel; Calderón-Salinas, José Victor; Villegas-Sepúlveda, Nicolás; Saucedo-Cárdenas, Odila; De Nova-Ocampo, Mónica; Valdés, Jesús

    2012-01-01

    The splicing of the N exon in the pre-mRNA coding for the RE1-silencing transcription factor (REST) results in a truncated protein that modifies the expression pattern of some of its target genes. A weak 3'ss, three alternative 5'ss (N4-, N50-, and N62-5'ss) and a variety of putative target sites for splicing regulatory proteins are found around the N exon; two GGGG codes (G2-G3) and a poly-Uridine tract (N-PU) are found in front of the N50-5'ss. In this work we analyzed some of the regulatory factors and elements involved in the preferred selection of the N50-5'ss (N50 activation) in the small cell lung cancer cell line H69. Wild type and mutant N exon/β-globin minigenes recapitulated N50 exon splicing in H69 cells, and showed that the N-PU and the G2-G3 elements are required for N50 exon splicing. Biochemical and knockdown experiments identified these elements as U2AF65 and hnRNP H targets, respectively, and that they are also required for N50 exon activation. Compared to normal MRC5 cells, and in keeping with N50 exon activation, U2AF65, hnRNP H and other splicing factors were highly expressed in H69 cells. CLIP experiments revealed that hnRNP H RNA-binding occurs first and is a prerequisite for U2AF65 RNA binding, and EMSA and CLIP experiments suggest that U2AF65-RNA recognition displaces hnRNP H and helps to recruit other splicing factors (at least U1 70K) to the N50-5'ss. Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5'ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes. PMID:22792276

  2. Small-Protein-Stabilized Semiconductor Nanoprobe for Targeted Imaging of Cancer Cells.

    PubMed

    Zhao, Ning; Liu, Siyu; Jiang, Qike; Lan, Tian; Cheng, Zhen; Liu, Hongguang

    2016-07-01

    Recently, semiconductor nanoparticles such as quantum dots (QDs) have attracted significant attention for bioimaging. Complex chemical functionalization, surface modification, and bioconjugation chemistry are generally required to tag biomolecules to QDs for imaging of different biomarkers. In this study, we report a simple method for production of QDs stabilized by the small protein, Affibody (AF-QDs) for fluorescent imaging of the human epidermal growth factor receptor type 2 (HER2) in human A549 lung cancer cells. This one-pot synthesis of AF-QDs avoids complex chemical conjugation procedures and demonstrates a promising approach for the preparation of fluorescent nanoprobes for imaging of cancer targets. PMID:27123671

  3. Molecular genetic analysis of U2AF59 in Schizosaccharomyces pombe: differential sensitivity of introns to mutational inactivation.

    PubMed Central

    Romfo, C M; Lakhe-Reddy, S; Wise, J A

    1999-01-01

    The large subunit of the mammalian U2AF heterodimer (U2AF65) is essential for splicing in vitro. To expand our understanding of how this protein functions in vivo, we have created a null allele of the gene encoding the Schizosaccharomyces pombe ortholog, U2AF59, and employed it in a variety of genetic complementation assays. First, analysis of an extensive series of double amino acid substitutions indicates that this splicing factor is surprisingly refractory to mutations. Second, despite extensive structural conservation, we find that metazoan large subunit orthologs cannot substitute in vivo for fission yeast U2AF59. Third, because the activity of U2AF65 in vitro involves binding to the 3' polypyrimidine tract, we examined the splicing of introns containing or lacking this feature in a U2AF59 mutant described here as well as a previously isolated temperature-sensitive mutant (Potashkin et al., 1993, Science 262:573-575). Our data indicate that all four introns tested, including two that lack extensive runs of pyrimidines between the branchpoint and 3' splice site, show splicing defects upon shifting to the nonpermissive condition. In all cases, splicing is blocked prior to the first transesterification reaction in the mutants, consistent with the role inferred for human U2AF65 based on in vitro experiments. PMID:9917066

  4. In vivo diagnosis of colonic precancer and cancer using near-infrared autofluorescence spectroscopy and biochemical modeling

    NASA Astrophysics Data System (ADS)

    Shao, Xiaozhuo; Zheng, Wei; Huang, Zhiwei

    2011-06-01

    The aim of this study is to evaluate the biochemical foundation and clinical capability of an image-guided near-infrared (NIR) autofluorescence (AF) spectroscopy technique for in vivo diagnosis of colonic malignancies during clinical colonoscopy. A novel endoscopic fiber-optic AF system was utilized for in vivo NIR AF measurements at 785 nm excitation. A total of 263 in vivo NIR AF spectra of colonic tissues were measured from 100 patients, in which 164 spectra were from benign tissue (116 normal and 48 hyperplastic polyps), 34 spectra were from precancer (adenomatous polyps), and 65 spectra were from cancer. The non-negativity constrained least squares minimization biochemical modeling was explored to estimate the biochemical compositions of colonic tissue using nine basis reference spectra from the representative biochemicals (i.e., collagen I, elastin, β-nicotinamide adenine dinucleotide, flavin adenine dinucleotide, L-tryptophan, hematoporphyrin, 4-pyridoxic acid, pyridoxal 5'-phosphate, and water) associated with structural or cellular metabolic progression in colonic precancer and cancer. High-quality in vivo NIR AF spectra in the spectral range of 810 to 1000 nm were acquired from colonic benign, precancerous, and cancerous mucosa under white-light reflectance endoscopic imaging guidance. Partial least squares discriminant analysis, together with the leave-one tissue site-out, cross validation on in vivo NIR AF spectra yields diagnostic sensitivities of 85.4%, 76.5%, and 84.6%, and specificities of 89.9%, 93.4%, and 91.4%, respectively, for classification of benign, precancer, and cancer in the colon. This work demonstrates that image-guided NIR AF spectroscopy in conjunction with biochemical modeling has promising potential for improving in vivo detection and diagnosis of colonic precancer and cancer during clinical colonoscopic screening.

  5. Racial Differences in Quality of Anticoagulation Therapy for Atrial Fibrillation (from the TREAT-AF Study).

    PubMed

    Yong, Celina; Azarbal, Farnaz; Abnousi, Freddy; Heidenreich, Paul A; Schmitt, Susan; Fan, Jun; Than, Claire T; Ullal, Aditya J; Yang, Felix; Phibbs, Ciaran S; Frayne, Susan M; Ho, P Michael; Shore, Supriya; Mahaffey, Kenneth W; Turakhia, Mintu P

    2016-01-01

    The influence of race on quality of anticoagulation control is not well described. We examined the association between race, international normalized ratio (INR) monitoring intensity, and INR control in warfarin-treated patients with atrial fibrillation (AF). Using data from the Veterans Health Administration (VHA), we performed a retrospective cohort study of 184,161 patients with a new diagnosis of AF/flutter from 2004 to 2012 who received any VHA prescription within 90 days of diagnosis. The primary predictor was race, ascertained from multiple VHA and linked Medicare demographic files. The primary outcome was first-year and long-term time in therapeutic range (TTR) of INR 2.0 to 3.0. Secondary outcomes were INR monitoring intensity and warfarin persistence. Of the 116,021 patients who received warfarin in the cohort, INR monitoring intensity was similar across racial groups. However, TTR was lowest in blacks and highest in whites (first year 0.49 ± 0.23 vs 0.57 ± 0.21, p <0.001; long term 0.52 ± 0.20 vs 0.59 ± 0.18, p <0.001); 64% of whites and 49% of blacks had long-term TTR >55% (p <0.001). After adjusting for site and patient-level covariates, black race was associated with lower first-year and long-term TTRs (4.2% and 4.1% below the conditional mean, relative to whites; p <0.0001 for both). One-year warfarin persistence was slightly lower in blacks compared to whites (58% vs 60%, p <0.0001). In conclusion, in patients with AF anticoagulated with warfarin, differences in INR control are most evident among blacks, underscoring the need to determine if other types of intensive management or warfarin alternatives may be necessary to improve anticoagulation among vulnerable AF populations. PMID:26552504

  6. Oblongionosides A-F, megastigmane glycosides from the leaves of Croton oblongifolius Roxburgh.

    PubMed

    Takeshige, Yuya; Kawakami, Susumu; Matsunami, Katsuyoshi; Otsuka, Hideaki; Lhieochaiphant, Duangporn; Lhieochaiphant, Sorasak

    2012-08-01

    From the 1-BuOH-soluble fraction of a MeOH extract of the leaves of Croton oblongifolius Roxburgh, collected in Chiang Mai, Thailand, six megastigmane glycosides, named oblongionosides A-F were isolated together with eight known compounds, and their structures elucidated on the basis of spectroscopic data. Absolute structures were determined by HPLC analyses and application of the modified Mosher's method. PMID:22683317

  7. Experimental test of macroscopic models for exchange anisotropy in FM/AF bilayers

    NASA Astrophysics Data System (ADS)

    Rezende, S. M.; Azevedo, A.; de Aguiar, F. M.; Lucena, M. A.; Fermin, J. R.; Parkin, S. S. P.

    2004-05-01

    Ferromagnetic resonance measurements in two series of ferromagnetic (FM)/antiferromagnetic (AF) bilayer samples of NiFe( t)/NiO and CoFe( t)/IrMn have been used to test macroscopic models for exchange anisotropy. The domain-wall model incorporating a rotatable anisotropy field is the one that best fits the data. All fields of interfacial origin extracted from the fits show the predicted 1 t dependence with the FM layer thickness.

  8. Cancer Statistics

    MedlinePlus

    ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ...

  9. Colon cancer

    MedlinePlus

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  10. Cancer Vaccines

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  11. Cervical Cancer

    MedlinePlus

    ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ...

  12. Cancer Staging

    MedlinePlus

    ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ... Role in Cancer Research Intramural Research Extramural Research Bioinformatics and Cancer NCI-Designated Cancer Centers Frederick National ...

  13. Metastatic Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  14. The Splicing Factor U2AF Small Subunit Is Functionally Conserved between Fission Yeast and Humans

    PubMed Central

    Webb, Christopher J.; Wise, Jo Ann

    2004-01-01

    The small subunit of U2AF, which functions in 3′ splice site recognition, is more highly conserved than its heterodimeric partner yet is less thoroughly investigated. Remarkably, we find that the small subunit of Schizosaccharomyces pombe U2AF (U2AFSM) can be replaced in vivo by its human counterpart, demonstrating that the conservation extends to function. Precursor mRNAs accumulate in S. pombe following U2AFSM depletion in a time frame consistent with a role in splicing. A comprehensive mutational analysis reveals that all three conserved domains are required for viability. Notably, however, a tryptophan in the pseudo-RNA recognition motif implicated in a key contact with the large subunit by crystallographic data is dispensable whereas amino acids implicated in RNA recognition are critical. Mutagenesis of the two zinc-binding domains demonstrates that they are neither equivalent nor redundant. Finally, two- and three-hybrid analyses indicate that mutations with effects on large-subunit interactions are rare whereas virtually all alleles tested diminished RNA binding by the heterodimer. In addition to demonstrating extraordinary conservation of U2AF small-subunit function, these results provide new insights into the roles of individual domains and residues. PMID:15121844

  15. In vivo role of the HNF4α AF-1 activation domain revealed by exon swapping

    PubMed Central

    Briançon, Nadège; Weiss, Mary C

    2006-01-01

    The gene encoding the nuclear receptor hepatocyte nuclear factor 4α (HNF4α) generates isoforms HNF4α1 and HNF4α7 from usage of alternative promoters. In particular, HNF4α7 is expressed in the pancreas whereas HNF4α1 is found in liver, and mutations affecting HNF4α function cause impaired insulin secretion and/or hepatic defects in humans and in tissue-specific ‘knockout' mice. HNF4α1 and α7 isoforms differ exclusively by amino acids encoded by the first exon which, in HNF4α1 but not in HNF4α7, includes the activating function (AF)-1 transactivation domain. To investigate the roles of HNF4α1 and HNF4α7 in vivo, we generated mice expressing only one isoform under control of both promoters, via reciprocal swapping of the isoform-specific first exons. Unlike Hnf4α gene disruption which causes embryonic lethality, these ‘α7-only' and ‘α1-only' mice are viable, indicating functional redundancy of the isoforms. However, the former show dyslipidemia and preliminary results indicate impaired glucose tolerance for the latter, revealing functional specificities of the isoforms. These ‘knock-in' mice provide the first test in vivo of the HNF4α AF-1 function and have permitted identification of AF-1-dependent target genes. PMID:16498401

  16. Fracture Growth Testing of Titanium 6AL-4V in AF-M315E

    NASA Technical Reports Server (NTRS)

    Sampson, Jeffrey W.; Martinez, Jonathan; McLean, Christopher

    2015-01-01

    The Green Propellant Infusion Mission (GPIM) will demonstrate the performance of AF-M315E monopropellant in orbit. Flight certification requires a safe-life analysis of the titanium alloy fuel tank to ensure inherent flaws will not cause failure during the design life. Material property inputs for this analysis require testing to determine the stress intensity factor for environmentally-assisted cracking (K (sub EAC)) of Ti 6Al-4V in combination with the AF-M315E monopropellant. Testing of single-edge notched specimens SE(B) representing the bulk tank membrane and weld material were performed in accordance with ASTM E1681. Specimens with fatigue pre-cracks were loaded into test fixtures so that the crack tips were exposed to the monopropellant at 50 degrees Centigrade for a duration of 1,000 hours. Specimens that did not fail during exposure were opened to inspect the crack surfaces for evidence of crack growth. The threshold stress intensity value, KEAC, is the highest applied stress intensity that produced neither a failure of the specimen during the exposure nor showed evidence of crack growth. The threshold stress intensity factor of the Ti 6Al-4V forged tank material when exposed to AF-M315E monopropellant was found to be at least 22.0 kilopounds per square inch. The stress intensity factor of the weld material was at least 31.3 kilopounds per square inch.

  17. Meeting in Florida: Using Asymmetric Flow Field-Flow Fractionation (AF4) to Determine C60 Colloidal Size Distributions

    EPA Science Inventory

    The study of nanomaterials in environmental systems requires robust and specific analytical methods. Analytical methods which discriminate based on particle size and molecular composition are not widely available. Asymmetric Flow Field-Flow Fractionation (AF4) is a separation...

  18. [3H]AF-DX 116 labels subsets of muscarinic cholinergic receptors in rat brain and heart.

    PubMed

    Wang, J X; Roeske, W R; Gulya, K; Wang, W; Yamamura, H I

    1987-10-01

    The in vitro binding properties of the novel muscarinic antagonist [3H]AF-DX 116 were studied using a rapid filtration technique. Association and dissociation rates of [3H]AF-DX 116 binding were rapid at 25 degrees C (2.74 and 2.70 X 10(7) min-1 M-1 for K+1; 0.87 and 0.93 min-1 for k-1) but 20-40 times slower at 0-4 degrees C (0.13 and 0.096 X 10(7) min-1 M-1 for k+1; 0.031 and 0.022 min-1 for k-1 in cerebral cortical and cardiac membranes, respectively). Kinetic dissociation constants (Kds) were estimated to be 31.8 nM and 30.9 nM at 25 degrees C; 23.1 nM and 0-4 degrees C for the cerebral cortex and heart, respectively. In saturation studies, [3H]AF-DX 116 labeled 29 percent of the total [3H](-)QNB binding sites in the cerebral cortical membranes and 87 percent in the cardiac membranes, with Kd values of 28.9 nM and 17.9 nM, respectively. Muscarinic antagonists inhibited [3H]AF-DX 116 binding in a rank order of potency of atropine greater than dexetimide greater than AF-DX 116 greater than PZ greater than levetimide in both tissues. Except for PZ/[3H]AF-DX 116 and AF-DX 116/[3H]AF-DX 116 in the cerebral cortex, all the antagonist competition curves had Hill coefficients close to one. Carbachol and oxotremorine produced shallow inhibition curves against [3H]AF-DX 116 binding in both tissues. Regional distribution studies with [3H](-)QNB, [3H]PZ and [3H]AF-DX 116 showed that most of the muscarinic receptors in the cerebral cortex, hippocampus, nucleus accumbens and corpus striatum are of the M1 subtype while those in the brainstem, cerebellum and other lower brain regions are of the M2 subtype. These results indicate that [3H]AF-DX 116 is a useful probe for the study of heterogeneity of muscarinic cholinergic receptors. PMID:3657382

  19. Vulva cancer

    MedlinePlus

    ... Cancer - perineum; Cancer - vulvar; Genital warts - vulvar cancer; HPV - vulvar cancer ... is rare. Risk factors include: Human papilloma virus (HPV, or genital warts ) infection in women under age ...

  20. Cloning of Caenorhabditis U2AF65: an alternatively spliced RNA containing a novel exon.

    PubMed Central

    Zorio, D A; Lea, K; Blumenthal, T

    1997-01-01

    The U2 small nuclear ribonucleoprotein particle (snRNP) auxiliary factor, U2AF, is an essential splicing factor required for recognition of the polypyrimidine tract and subsequent U2 snRNP assembly at the branch point. Because Caenorhabditis elegans introns lack both polypyrimidine tract and branch point consensus sequences but have a very highly conserved UUUUCAG/R consensus at their 3' splice sites, we hypothesized that U2AF might serve to recognize this sequence and thus promote intron recognition in C. elegans. Here we report the cloning of the gene for the large subunit of U2AF, uaf-1. Three classes of cDNA were identified. In the most abundant class the open reading frame is similar to that for the U2AF65 from mammals and flies. The remaining two classes result from an alternative splicing event in which an exon containing an in-frame stop codon is inserted near the beginning of the second RNA recognition motif. However, this alternative mRNA is apparently not translated. Interestingly, the inserted exon contains 10 matches to the 3' splice site consensus. To determine whether this feature is conserved, we sequenced uaf-1 from the related nematode Caenorhabditis briggsae. It is composed of six exons, including an alternatively spliced third exon interrupting the gene at the same location as in C. elegans. uaf-1 is contained in an operon with the rab-18 gene in both species. Although the alternative exons from the two species are not highly conserved and would not encode related polypeptides, the C. briggsae alternative exon has 18 matches to the 3' splice site consensus. We hypothesize that the array of 3' splice site-like sequences in the pre-mRNA and alternatively spliced exon may have a regulatory role. The alternatively spliced RNA accumulates at high levels following starvation, suggesting that this RNA may represent an adaption for reducing U2AF65 levels when pre-mRNA levels are low. PMID:9001248

  1. Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

    PubMed

    Potpara, Tatjana S; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S; Polovina, Marija M; Petranov, Stanislav L; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y H

    2016-01-01

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID:26869284

  2. Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia.

    PubMed Central

    Prasad, R; Yano, T; Sorio, C; Nakamura, T; Rallapalli, R; Gu, Y; Leshkowitz, D; Croce, C M; Canaani, E

    1995-01-01

    The ALLI gene, located at chromosome band 11q23, is involved in acute leukemia through a series of chromosome translocations and fusion to a variety of genes, most frequently to A4 and AF9. The fused genes encode chimeric proteins proteins. Because the Drosophila homologue of ALL1, trithorax, is a positive regulator of homeotic genes and acts at the level of transcription, it is conceivable that alterations in ALL1 transcriptional activity may underlie its action in malignant transformation. To begin studying this, we examined the All1, AF4, AF9, and AF17 proteins for the presence of potential transcriptional regulatory domains. This was done by fusing regions of the proteins to the yeast GAL4 DNA binding domain and assaying their effect on transcription of a reporter gene. A domain of 55 residues positioned at amino acids 2829-2883 of ALL1 was identified as a very strong activator. Further analysis of this domain by in vitro mutagenesis pointed to a core of hydrophobic and acidic residues as critical for the activity. An ALL1 domain that repressed transcription of the reporter gene coincided with the sequence homologous to a segment of DNA methyltransferase. An AF4 polypeptide containing residues 480-560 showed strong activation potential. The C-terminal segment of AF9 spanning amino acids 478-568 transactivated transcription of the reporter gene in HeLa but not in NIH 3T3 cells. These results suggest that ALL1, AF4, and probably AF9 interact with the transcriptional machinery of the cell. Images Fig. 1 Fig. 4 Fig. 5 PMID:8618864

  3. Molecular characterization of a rare MLL-AF4 (MLL-AFF1) fusion rearrangement in infant leukemia.

    PubMed

    Bizarro, Susana; Cerveira, Nuno; Correia, Cecília; Lisboa, Susana; Peixoto, Ana; Norton, Lucília; Teixeira, Manuel R

    2007-10-01

    The t(4;11)(q21;q23) involving the genes MLL and AF4 (alias for AFF1) is detected in 50-70% of infant leukemia. We characterize at both the DNA and RNA level a rare MLL-AF4 fusion transcript identified in a 15-month-old girl with acute lymphoblastic leukemia. Direct sequence analysis of the reverse transcriptase-polymerase chain reaction product showed an in-frame fusion between MLL exon 9 and AF4 exon 6. We further demonstrated that the genomic breakpoints were located 1,553 bp downstream of MLL exon 9 and 1,239 bp upstream of AF4 exon 6. Four Alu repeats were detected in MLL intron 9 and two Alu repeats and one LINE1 repetitive element were identified downstream of AF4 exon 5. Finally, a 9-bp polypurine (A) tract and an 8-bp polypyrimidine (T) tract were found flanking the translocation breakpoint. In summary, we have characterized at both the RNA and the DNA level a rare MLL-AF4 fusion variant that was presumably mediated by Alu repeats or polypurine and polypyrimidine tracts located in the vicinity of genomic breakpoints. PMID:17889710

  4. Potentiation of estrogen receptor activation function 1 (AF-1) by Src/JNK through a serine 118-independent pathway.

    PubMed

    Feng, W; Webb, P; Nguyen, P; Liu, X; Li, J; Karin, M; Kushner, P J

    2001-01-01

    Estrogen receptor (ER) is activated either by ligand or by signals from tyrosine kinase-linked cell surface receptors. We investigated whether the nonreceptor Src tyrosine kinase could affect ER activity. Expression of constitutively active Src or stimulation of the endogenous Src/JNK pathway enhances transcriptional activation by the estrogen-ER complex and strongly stimulates the otherwise weak activation by the unliganded ER and the tamoxifen-ER complex. Src affects ER activation function 1 (AF-1), and not ER AF-2, and does so through its tyrosine kinase activity. This effect of Src is mediated partly through a Raf/mitogen-activated ERK kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) signaling cascade and partly through a MEKK/JNKK/JNK cascade. Although, as previously shown, Src action through activated ERK stimulates AF-1 by phosphorylation at S118, Src action through activated JNK neither leads to phosphorylation of S118 nor requires S118 for its action. We therefore suggest that the Src/JNK pathway enhances AF-1 activity by modification of ER AF-1-associated proteins. Src potentiates activation functions in CREB-binding protein (CBP) and glucocorticoid receptor interacting protein 1 (GRIP1), and we discuss the possibility that the Src/JNK pathway enhances the activity of these coactivators, which are known to mediate AF-1 action. PMID:11145737

  5. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

    PubMed Central

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  6. AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment.

    PubMed

    Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

    2016-01-01

    The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

  7. AhR ligand Aminoflavone inhibits α6-integrin expression and breast cancer sphere-initiating capacity.

    PubMed

    Brantley, Eileen; Callero, Mariana A; Berardi, Damian E; Campbell, Petreena; Rowland, Leah; Zylstra, Dain; Amis, Louisa; Yee, Michael; Simian, Marina; Todaro, Laura; Loaiza-Perez, Andrea I; Soto, Ubaldo

    2016-06-28

    Traditional chemotherapies debulk tumors but fail to produce long-term clinical remissions due to their inability to eradicate tumor-initiating cells (TICs). This necessitates therapy with activity against the TIC niche. Αlpha6-integrin (α6-integrin) promotes TIC growth. In contrast, aryl hydrocarbon receptor (AhR) signaling activation impedes the formation of mammospheres (clusters of cells enriched for TICs). We investigated the ability of AhR agonist Aminoflavone (AF) and AF pro-drug (AFP464) to disrupt mammospheres derived from breast cancer cells and a M05 mammary mouse model of breast cancer respectively. We further examined the capacity of AF and AFP464 to exhibit anticancer activity and modulate the expression of 'stemness' genes including α6-integrin using immunofluorescence, flow cytometry and qRT-PCR analysis. AF disrupted mammospheres and prevented secondary mammosphere formation. In contrast, AF did not disrupt mammospheres derived from AhR ligand-unresponsive MCF-7 cells. AFP464 treatment suppressed M05 tumor growth and disrupted corresponding mammospheres. AF and AFP464 reduced the expression and percentage of cells that stained for 'stemness' markers including α6-integrin in vitro and in vivo respectively. These data suggest AFP464 thwarts bulk breast tumor and TIC growth via AhR agonist-mediated α6-integrin inhibition. PMID:26996297

  8. Cancer Statistics: Endometrial Cancer

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 60,050 % of All New Cancer Cases 3.6% Estimated Deaths in 2016 10,470 % of All Cancer ... of This Cancer : In 2013, there were an estimated 635,437 women living with endometrial cancer in ...

  9. Tristetraprolin Represses Estrogen Receptor α Transactivation in Breast Cancer Cells*

    PubMed Central

    Barrios-García, Tonatiuh; Tecalco-Cruz, Angeles; Gómez-Romero, Vania; Reyes-Carmona, Sandra; Meneses-Morales, Iván; León-Del-Río, Alfonso

    2014-01-01

    Estrogen receptor α (ERα) mediates the effects of 17β-estradiol (E2) in normal mammary gland, and it is a key participant in breast cancer tumor development. ERα transactivation activity is mediated by the synergistic interaction of two domains designated AF1 and AF2. The function of AF2 is to recruit coactivator and corepressor proteins that allow ERα to oscillate between the roles of transcriptional activator and repressor. In contrast, the mechanism responsible for AF-1 transcriptional activity is not completely understood. In this study, we identified tristetraproline (TTP) as a novel ERα-associated protein. TTP expression in MCF7 cells repressed ERα transactivation and reduced MCF7 cell proliferation and the ability of the cells to form tumors in a mouse model. We show that TTP transcriptional activity is mediated through its recruitment to the promoter region of ERα target genes and its interaction with histone deacetylases, in particular with HDAC1. TTP expression attenuates the coactivating activity of SRC-1, suggesting that exchange between TTP and other coactivators may play an important role in fine-tuning ERα transactivation. These results indicate that TTP acts as a bona fide ERα corepressor and suggest that this protein may be a contributing factor in the development of E2-dependent tumors in breast cancer. PMID:24737323

  10. AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.

    PubMed

    Fisher, Abraham; Bezprozvanny, Ilya; Wu, Lili; Ryskamp, Daniel A; Bar-Ner, Nira; Natan, Niva; Brandeis, Rachel; Elkon, Hanoch; Nahum, Victoria; Gershonov, Eitan; LaFerla, Frank M; Medeiros, Rodrigo

    2016-01-01

    We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on the M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (p-ERK1/2, p-CREB). AF710B (1-30 µg/kg, p.o.) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its antiamnesic properties, AF710B (at 30 nM), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µM) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice, AF710B (10 µg/kg, i.p./daily/2 months) (i) mitigated cognitive impairments in the Morris water maze; (ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ40, Aβ42, plaques and tau pathologies. AF710B differs from conventional σ1 and M1 muscarinic (orthosteric, allosteric or bitopic) agonists. These results highlight AF710B as a potential treatment for Alzheimer's disease (e.g. improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies. PMID:26606130

  11. The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models.

    PubMed

    Dutta, S; Krause, A; Vosberg, S; Herold, T; Ksienzyk, B; Quintanilla-Martinez, L; Tizazu, B; Chopra, M; Graf, A; Krebs, S; Blum, H; Greif, P A; Vetter, A; Metzeler, K; Rothenberg-Thurley, M; Schneider, M R; Dahlhoff, M; Spiekermann, K; Zimber-Strobl, U; Wolf, E; Bohlander, S K

    2016-05-01

    The CALM/AF10 fusion gene is found in various hematological malignancies including acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia and malignant lymphoma. We have previously identified the leukemia stem cell (LSC) in a CALM/AF10-driven murine bone marrow transplant AML model as B220+ lymphoid cells with B-cell characteristics. To identify the target cell for leukemic transformation or 'cell of origin of leukemia' (COL) in non-disturbed steady-state hematopoiesis, we inserted the CALM/AF10 fusion gene preceded by a loxP-flanked transcriptional stop cassette into the Rosa26 locus. Vav-Cre-induced panhematopoietic expression of the CALM/AF10 fusion gene led to acute leukemia with a median latency of 12 months. Mice expressing CALM/AF10 in the B-lymphoid compartment using Mb1-Cre or CD19-Cre inducer lines did not develop leukemia. Leukemias had a predominantly myeloid phenotype but showed coexpression of the B-cell marker B220, and had clonal B-cell receptor rearrangements. Using whole-exome sequencing, we identified an average of two to three additional mutations per leukemia, including activating mutations in known oncogenes such as FLT3 and PTPN11. Our results show that the COL for CALM/AF10 leukemia is a stem or early progenitor cell and not a cell of B-cell lineage with a phenotype similar to that of the LSC in CALM/AF10+ leukemia. PMID:26686248

  12. Quality control in boar semen production by use of the FACSCount AF system.

    PubMed

    Christensen, Preben; Knudsen, Dorte B; Wachmann, Henrik; Madsen, Mads T

    2004-10-01

    A simple and rapid flow cytometric method has recently been developed for simultaneous determination of sperm concentration and viability in semen from domestic animals. Use of SYBR-14 trade mark in combination with propidium iodide (PI) allows estimation of the proportion of live sperm (viability). An internal standard of fluorescent microspheres (beads) makes it possible to determine the sperm concentration during the same analysis. In the first experiment, the relationship between sperm viability and litter size was investigated. The second experiment explored whether a smaller variation in the number of motile sperm per insemination dose could be obtained using the FACSCount AF flow cytometer than using a spectrophotometer. Results in the first experiment show that sperm viability is closer related to litter size than is the traditionally used motility parameter. Although the flow cytometer is precise and objective, a limited effect on litter size should be anticipated if ejaculates are selected for insemination according to the percentage of viable sperm. However, the present trial used large insemination doses (2.3 x 10(9) motile sperm/dose) which partially compensate for the differences in motility and viability between boars and ejaculates. In the second experiment it was found that variation in the number of motile sperm per insemination dose could be reduced significantly if the FACSCount AF flow cytometer rather than the Corning 254 spectrophotometer was used for determination of sperm concentration in the raw semen. It is concluded that the FACSCount AF flow cytometer is a strong tool for improvement of the quality control in artificial insemination (AI) centres. PMID:15325548

  13. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  14. Ovarian cancer

    MedlinePlus

    Cancer - ovaries ... Ovarian cancer is the fifth most common cancer among women. It causes more deaths than any other type of female reproductive organ cancer. The cause of ovarian cancer is unknown. Risk ...

  15. Oral Cancer

    MedlinePlus

    ... HUMAN SERVICES National Institutes of Health About Oral Cancer Oral cancer includes cancers of the mouth and pharynx (the back of the throat). Oral cancer accounts for roughly two percent of all cancers ...

  16. Development of a Radiolabeled Peptide-Based Probe Targeting MT1-MMP for Breast Cancer Detection

    PubMed Central

    Min, Kaiyin; Ji, Bin; Zhao, Min; Ji, Tiefeng; Chen, Bin; Fang, Xuedong; Ma, Qingjie

    2015-01-01

    Breast cancer is one of the most frequent and aggressive primary tumors among women of all races. Matrix metalloproteinase (MMPs), a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases, is overexpressed in varieties of diseases including breast cancer. Therefore, noninvasive visualization and quantification of MMP in vivo are of great interest in basic research and clinical application for breast cancer early diagnosis. Herein, we developed a 99mTc labeled membrane type I matrix metalloproteinase (MT1-MMP) specific binding peptide, [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS), for in vivo detection of MDA-MB-231 breast tumor by single photon emission computed tomography (SPECT). [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) demonstrated nice biostability and high MT1-MMP binding affinity in vitro and in vivo. Tumor-to-muscle ratio was found to reach to the highest (4.17±0.49) at 2 hour after intravenously administration of [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) into MDA-MB-231 tumor bearing mice. Overall, [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) demonstrated great potential for MT1-MMP targeted detection in vivo and it would be a promising molecular imaging probe that are probably beneficial to breast cancer early diagnoses. PMID:26437463

  17. The strainrange partitioning behavior of an advanced gas turbine disk alloy, AF2-1DA

    NASA Technical Reports Server (NTRS)

    Halford, G. R.; Nachtigall, A. J.

    1979-01-01

    The low-cycle, creep-fatigue characteristics of the advanced gas turbine disk alloy, AF2-1DA have been determined at 1400 F and are presented in terms of the method of strainrange partitioning (SRP). The mean stresses which develop in the PC and CP type SRP cycles at the lowest inelastic strainrange were observed to influence the cyclic lives to a greater extent than the creep effects and hence interfered with a conventional interpretation of the results by SRP. A procedure is proposed for dealing with the mean stress effects on life which is compatible with SRP.

  18. Direct interactions in the recognition between the environmental estrogen bisphenol AF and human serum albumin.

    PubMed

    Yang, Lijun; Lv, Junna; Wang, Xin; Zhang, Jing; Li, Qi; Zhang, Tingting; Zhang, Zhenzhen; Zhang, Lei

    2015-08-01

    Bisphenol AF (BPAF) was used as a model compound to investigate the binding mechanism between the endocrine disrupting compound and human serum albumin (HSA) using multispectroscopic techniques and molecular modeling method at the protein level. The results indicated that BPAF was indeed bound to HSA and located in the hydrophobic pocket of HSA on subdomain IIA through hydrogen bond and van der Waals interactions. The fluorescence quenching data showed that the binding of BPAF and HSA quenched the intrinsic fluorescence of HSA, and the static quenching constants were acquired. PMID:25694370

  19. Spectral analysis of LBV stars in M31: AF And and Var 15

    NASA Astrophysics Data System (ADS)

    Valeev, A. F.; Sholukhova, O.; Fabrika, S.

    2015-01-01

    We study spectra of two bona fide LBV stars in M31: AF And and Var 15. The spectra were obtained with the 6-m telescope (Russia) from 2005 to 2012. The model spectra were calculated with the CMFGEN code. We have not found strong changes in the spectra of the LBV stars in that time interval, however a certain variability has been detected. We estimate the star and wind parameters, such as luminosity, temperature, raduis, mass loss rate, escape velocity, hydrogen content, and reddening. We study the stars on the Hertzsprung-Russell diagram and find their initial masses using evolutionary tracks by Meynet et al. (1994).

  20. 6 Common Cancers - Breast Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  1. 6 Common Cancers - Breast Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents ... slow her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth ...

  2. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... of colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  3. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  4. An extended U2AF65–RNA-binding domain recognizes the 3′ splice site signal

    PubMed Central

    Agrawal, Anant A.; Salsi, Enea; Chatrikhi, Rakesh; Henderson, Steven; Jenkins, Jermaine L.; Green, Michael R.; Ermolenko, Dmitri N.; Kielkopf, Clara L.

    2016-01-01

    How the essential pre-mRNA splicing factor U2AF65 recognizes the polypyrimidine (Py) signals of the major class of 3′ splice sites in human gene transcripts remains incompletely understood. We determined four structures of an extended U2AF65–RNA-binding domain bound to Py-tract oligonucleotides at resolutions between 2.0 and 1.5 Å. These structures together with RNA binding and splicing assays reveal unforeseen roles for U2AF65 inter-domain residues in recognizing a contiguous, nine-nucleotide Py tract. The U2AF65 linker residues between the dual RNA recognition motifs (RRMs) recognize the central nucleotide, whereas the N- and C-terminal RRM extensions recognize the 3′ terminus and third nucleotide. Single-molecule FRET experiments suggest that conformational selection and induced fit of the U2AF65 RRMs are complementary mechanisms for Py-tract association. Altogether, these results advance the mechanistic understanding of molecular recognition for a major class of splice site signals. PMID:26952537

  5. A novel 3′ splice site recognition by the two zinc fingers in the U2AF small subunit

    PubMed Central

    Yoshida, Hisashi; Park, Sam-Yong; Oda, Takashi; Akiyoshi, Taeko; Sato, Mamoru; Shirouzu, Mikako; Tsuda, Kengo; Kuwasako, Kanako; Unzai, Satoru; Muto, Yutaka; Urano, Takeshi; Obayashi, Eiji

    2015-01-01

    The pre-mRNA splicing reaction of eukaryotic cells has to be carried out extremely accurately, as failure to recognize the splice sites correctly causes serious disease. The small subunit of the U2AF heterodimer is essential for the determination of 3′ splice sites in pre-mRNA splicing, and several single-residue mutations of the U2AF small subunit cause severe disorders such as myelodysplastic syndromes. However, the mechanism of RNA recognition is poorly understood. Here we solved the crystal structure of the U2AF small subunit (U2AF23) from fission yeast, consisting of an RNA recognition motif (RRM) domain flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs are positioned side by side on the β sheet of the RRM domain. Further mutational analysis revealed that the ZFs bind cooperatively to the target RNA sequence, but the RRM domain acts simply as a scaffold to organize the ZFs and does not itself contact the RNA directly. This completely novel and unexpected mode of RNA-binding mechanism by the U2AF small subunit sheds light on splicing errors caused by mutations of this highly conserved protein. PMID:26215567

  6. The AF4-mimetic peptide, PFWT, induces necrotic cell death in MV4-11 leukemia cells

    PubMed Central

    Palermo, Christine M.; Bennett, Cecily A.; Winters, Amanda C.; Hemenway, Charles S.

    2008-01-01

    Despite ongoing success in the treatment of childhood acute lymphoblastic leukemia, patients harboring translocations involving the MLL gene at chromosome 11q23 remain resistant to treatment. To improve outcomes, novel therapeutics designed to target the unusual biology of these leukemias need to be developed. Previously, we identified an interaction between the two most common MLL fusion proteins, AF4 and AF9, and designed a synthetic peptide (PFWT) capable of disrupting this interaction. PFWT induced cell death in leukemia cells expressing MLL-AF4 with little effect on the colony forming potential of hematopoietic progenitor cells, suggesting the AF4–AF9 complex is an important pharmacological target for leukemia therapy and PFWT is a promising chemotherapeutic prototype. In these studies, we demonstrate that PFWT induces death by necrosis in MV4-11 cells. Cell death is characterized by rapid loss of plasma membrane integrity with maintenance of nuclear membrane integrity, and is independent of caspase activation, DNA fragmentation, and mitochondrial membrane depolarization. PFWT-mediated necrosis is inhibited by the serine protease inhibitor TLCK, suggesting this death pathway is regulated. Given the resistance of t(4;11) leukemias to conventional chemotherapeutic agents that induce apoptosis, further identification of the molecular events mediating this death process should uncover new avenues for therapeutic intervention. PMID:17875318

  7. Validation of the Risk Estimator Decision aid for Atrial Fibrillation (RED-AF) for Predicting 30-Day Adverse Events in Emergency Department Patients With Atrial Fibrillation

    PubMed Central

    Barrett, Tyler W.; Jenkins, Cathy A.; Self, Wesley H.

    2014-01-01

    Objective Nearly 70% of emergency departments (ED) visits for atrial fibrillation (AF) result in hospitalization. The incidence of serious 30-day adverse events following an ED evaluation for AF remains low. This study’s goal was to prospectively validate our previously reported Risk Estimator Decision aid for AF (RED-AF) model for estimating a patient’s risk of experiencing a 30-day adverse event. Methods This was a prospective cohort study, which enrolled a convenience sample of ED patients presenting with AF. RED-AF, previously derived from a retrospective cohort of 832 patients, assigns points based on age, sex, coexisting disease (heart failure, hypertension, chronic obstructive pulmonary disease), smoking, home medications (beta blocker, diuretic), physical examination findings (dyspnea, palpitations, peripheral edema), and adequacy of ED ventricular rate control. Primary outcome was occurrence of ≥1 AF-related adverse outcome (ED visits, rehospitalization, cardiovascular complications, death) within 30 days. We identified a clinically relevant threshold and measured RED-AF’s performance in this prospective cohort, assessing its calibration, discrimination, and diagnostic accuracy. Results The study enrolled 497 patients between June 2010 and February 2013. Of these, 120 (24%) had ≥1 adverse event within 30 days. A RED-AF score of 87 was identified as an optimal threshold, resulting in sensitivity (95% CI) and specificity (95%CI) of 96% (91–98) and 19% (15–23), respectively. Positive and negative predictive values were 27% (23–32) and 93% (85–97), respectively. The c-statistic for RED-AF was 0.65 (95% CI, 0.59 to 0.71). Conclusion In this separate validation cohort, RED-AF performed moderately well and similar to the original derivation cohort for identifying the risk of short-term AF-related adverse events in ED patients diagnosed with AF. PMID:25245277

  8. Intramuscular Innervation of Primate Extraocular Muscles: Unique Compartmentalization in Horizontal Recti

    PubMed Central

    da Silva Costa, Roberta Martins; Kung, Jennifer; Poukens, Vadims; Yoo, Lawrence; Tychsen, Lawrence

    2011-01-01

    Purpose. It has been proposed that the lateral rectus (LR), like many skeletal and craniofacial muscles, comprises multiple neuromuscular compartments subserving different physiological functions. To explore the anatomic potential of compartmentalization in all four rectus extraocular muscles (EOMs), evidence was sought of possible regional selectivity in intramuscular innervation of all rectus EOMs. Methods. Whole orbits of two humans and one macaque monkey were serially sectioned at 10 μm thickness and stained with Masson's trichrome. Three-dimensional reconstruction was performed of the intramuscular courses of motor nerves from the deep orbit to the anterior extents of their arborizations within all four rectus EOMs in each orbit. Results. Findings concorded in monkey and human orbits. Externally to the global surface of the lateral (LR) and medial rectus (MR) EOMs, motor nerve trunks bifurcated into approximately equal-sized branches before entering the global layer and observing a segregation of subsequent arborization into superior zones that exhibited minimal overlap along the length of the LR and only modest overlap for MR. In contrast, intramuscular branches of the superior and the nasal portion of the inferior rectus were highly mixed. Conclusions. Consistent segregation of intramuscular motor nerve arborization suggests functionally distinct superior and inferior zones within the horizontal rectus EOMs in both humans and monkeys. Reduced or absent compartmentalization in vertical rectus EOMs supports a potential functional role for differential innervation in horizontal rectus zones that could mediate previously unrecognized vertical oculorotary actions. PMID:21220556

  9. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection.

    PubMed

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-01-01

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes' status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors' detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

  10. AF-DHNN: Fuzzy Clustering and Inference-Based Node Fault Diagnosis Method for Fire Detection

    PubMed Central

    Jin, Shan; Cui, Wen; Jin, Zhigang; Wang, Ying

    2015-01-01

    Wireless Sensor Networks (WSNs) have been utilized for node fault diagnosis in the fire detection field since the 1990s. However, the traditional methods have some problems, including complicated system structures, intensive computation needs, unsteady data detection and local minimum values. In this paper, a new diagnosis mechanism for WSN nodes is proposed, which is based on fuzzy theory and an Adaptive Fuzzy Discrete Hopfield Neural Network (AF-DHNN). First, the original status of each sensor over time is obtained with two features. One is the root mean square of the filtered signal (FRMS), the other is the normalized summation of the positive amplitudes of the difference spectrum between the measured signal and the healthy one (NSDS). Secondly, distributed fuzzy inference is introduced. The evident abnormal nodes’ status is pre-alarmed to save time. Thirdly, according to the dimensions of the diagnostic data, an adaptive diagnostic status system is established with a Fuzzy C-Means Algorithm (FCMA) and Sorting and Classification Algorithm to reducing the complexity of the fault determination. Fourthly, a Discrete Hopfield Neural Network (DHNN) with iterations is improved with the optimization of the sensors’ detected status information and standard diagnostic levels, with which the associative memory is achieved, and the search efficiency is improved. The experimental results show that the AF-DHNN method can diagnose abnormal WSN node faults promptly and effectively, which improves the WSN reliability. PMID:26193280

  11. [Refractory primary myeloid sarcoma of the breast with MLL-AF9 rearrangement].

    PubMed

    Uchida, Emi; Watanabe, Ken; Oshikawa, Gaku; Sakashita, Chizuko; Kurosu, Tetsuya; Fukuda, Tetsuya; Arai, Ayako; Murakami, Naomi; Miura, Osamu; Yamamoto, Masahide

    2016-01-01

    A 28-year-old woman presented with a right breast mass and axillary lymphadenopathy. Biopsy of the breast mass revealed myeloid sarcoma (MS) staining positive for CD4, CD13, CD33, and CD68/KP-1. Bone marrow aspiration revealed leukemic cell infiltration (9%). Leukemic cells possessed cytogenetic abnormalities of +8 and t(9;11)(p22;q23) with +22 (lymph node only), and molecular analyses confirmed the MLL-AF9 fusion gene. After induction chemotherapy and 2(nd) consolidation therapy, complete remission was maintained. However, during consolidation radiotherapy for the breast mass, the disease progressed in both the breast and bone marrow. She received re-induction therapy and proceeded to allogeneic stem cell transplantation. However, the disease relapsed in the breast soon after transplantation, and she died from disease progression. Trisomy 8 and the MLL-AF9 fusion gene have been reported in cases with MS in the breast. Trisomy 22 found additionally and exclusively in the extramedullary lesion implies extramedullary progression of MS from the medullary site of origin and may have been associated with the distinctive therapy resistance of these lesions in our case. PMID:26861104

  12. Intracardiac impedance response during acute AF internal cardioversion using novel rectilinear and capacitor-discharge waveforms.

    PubMed

    Rababah, A S; Walsh, S J; Manoharan, G; Walsh, P R; Escalona, O J

    2016-07-01

    Intracardiac impedance (ICI) is a major determinant of success during internal cardioversion of atrial fibrillation (AF). However, there have been few studies that have examined the dynamic behaviour of atrial impedance during internal cardioversion in relation to clinical outcome. In this study, voltage and current waveforms captured during internal cardioversion of acute AF in ovine models using novel radiofrequency (RF) generated low-tilt rectilinear and conventional capacitor-discharge based shock waveforms were retrospectively analysed using a digital signal processing algorithm to investigate the dynamic behaviour of atrial impedance during cardioversion. The algorithm was specifically designed to facilitate the simultaneous analysis of multiple impedance parameters, including: mean intracardiac impedance (Z M), intracardiac impedance variance (ICIV) and impedance amplitude spectrum area (IAMSA) for each cardioversion event. A significant reduction in ICI was observed when comparing two successive shocks of increasing energy where cardioversion outcome was successful. In addition, ICIV and IAMSA variables were found to inversely correlate to the magnitude of energy delivered; with a stronger correlation found to the former parameter. In conclusion, ICIV and IAMSA have been evidenced as two key dynamic intracardiac impedance variables that may prove useful in better understanding of the cardioversion process and that could potentially act as prognostic markers with respect to clinical outcome. PMID:27328164

  13. Advanced Compatibility Characterization Of AF-M315E With Spacecraft Propulsion System Materials Project

    NASA Technical Reports Server (NTRS)

    McClure, Mark B.; Greene, Benjamin

    2014-01-01

    All spacecraft require propulsion systems for thrust and maneuvering. Propulsion systems can be chemical, nuclear, electrical, cold gas or combinations thereof. Chemical propulsion has proven to be the most reliable technology since the deployment of launch vehicles. Performance, storability, and handling are three important aspects of liquid chemical propulsion. Bipropellant systems require a fuel and an oxidizer for propulsion, but monopropellants only require a fuel and a catalyst for propulsion and are therefore simpler and lighter. Hydrazine is the state of the art propellant for monopropellant systems, but has drawbacks because it is highly hazardous to human health, which requires extensive care in handling, complex ground ops due to safety and environmental considerations, and lengthy turnaround times for reusable spacecraft. All users of hydrazine monopropellant must contend with these issues and their associated costs. The development of a new monopropellant, intended to replace hydrazine, has been in progress for years. This project will apply advanced techniques to characterize the engineering properties of materials used in AF-M315E propulsion systems after propellant exposure. AF-M315E monopropellant has been selected HQ's Green Propellant Infusion Mission (GPIM) to replace toxic hydrazine for improved performance and reduce safety and health issues that will shorten reusable spacecraft turn-around time. In addition, this project will fundamentally strengthen JSC's core competency to evaluate, use and infuse liquid propellant systems.

  14. Development of FDR-AF (Frictional Drag Reduction Anti-Fouling) Marine Coating

    NASA Astrophysics Data System (ADS)

    Lee, Inwon; Park, Hyun; Chun, Ho Hwan; GCRC-SOP Team

    2013-11-01

    In this study, a novel skin-friction reducing marine paint has been developed by mixing fine powder of PEO(PolyEthyleneOxide) with SPC (Self-Polishing Copolymer) AF (Anti-Fouling) paint. The PEO is well known as one of drag reducing agent to exhibit Toms effect, the attenuation of turbulent flows by long chain polymer molecules in the near wall region. The frictional drag reduction has been implemented by injecting such polymer solutions to liquid flows. However, the injection holes have been a significant obstacle to marine application. The present PEO-containing marine paint is proposed as an alternative to realize Toms effect without any hole on the ship surface. The erosion mechanism of SPC paint resin and the subsequent dissolution of PEO enable the controlled release of PEO solution from the coating. Various tests such as towing tank drag measurement of flat plate and turbulence measurement in circulating water tunnel demonstrated over 10% frictional drag reduction compared with conventional AF paint. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) through GCRC-SOP(No. 2011-0030013).

  15. Thyroid Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Thyroid Cancer Thyroid Cancer This is Cancer.Net’s Guide to Thyroid Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Overview Statistics Medical Illustrations Risk Factors Symptoms ...

  16. Breast Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Breast Cancer Breast Cancer This is Cancer.Net’s Guide to Breast Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer Overview Statistics Medical Illustrations Risk Factors Screening Symptoms ...

  17. Anal Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Anal Cancer Anal Cancer This is Cancer.Net’s Guide to Anal Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Anal Cancer Introduction Statistics Risk Factors and Prevention Screening ...

  18. Cancer Statistics: Pancreas Cancer

    MedlinePlus

    ... Series Pancreatic Cancer - Did you know that an estimated 46,000 Americans were diagnosed with pancreatic cancer ... at a Glance Show More At a Glance Estimated New Cases in 2016 53,070 % of All ...

  19. The planar cell polarity (PCP) protein Diversin translocates to the nucleus to interact with the transcription factor AF9

    SciTech Connect

    Haribaskar, Ramachandran; Puetz, Michael; Schupp, Birte; Skouloudaki, Kassiani; Bietenbeck, Andreas; Walz, Gerd; Schaefer, Tobias

    2009-09-11

    The planar cell polarity (PCP) pathway, a {beta}-catenin-independent branch of the Wnt signaling pathway, orients cells and their appendages with respect to the body axes. Diversin, the mammalian homolog of the Drosophila PCP protein Diego, acts as a molecular switch that blocks {beta}-catenin-dependent and promotes {beta}-catenin-independent Wnt signaling. We report now that Diversin, containing several nuclear localization signals, translocates to the nucleus, where it interacts with the transcription factor AF9. Both Diversin and AF9 block canonical Wnt signaling; however, this occurs independently of each other, and does not require nuclear Diversin. In contrast, AF9 strongly augments the Diversin-driven activation of c-Jun N-terminal kinase (JNK)-dependent gene expression in the nucleus, and this augmentation largely depends on the presence of nuclear Diversin. Thus, our findings reveal that components of the PCP cascade translocate to the nucleus to participate in transcriptional regulation and PCP signaling.

  20. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  1. A Comparison of Atrial Fibrillation Monitoring Strategies After Cryptogenic Stroke (from the Cryptogenic Stroke and Underlying AF Trial).

    PubMed

    Choe, William C; Passman, Rod S; Brachmann, Johannes; Morillo, Carlos A; Sanna, Tommaso; Bernstein, Richard A; Di Lazzaro, Vincenzo; Diener, Hans-Christoph; Rymer, Marilyn M; Beckers, Frank; Koehler, Jodi; Ziegler, Paul D

    2015-09-15

    Ischemic stroke cause remains undetermined in 30% of cases, leading to a diagnosis of cryptogenic stroke. Paroxysmal atrial fibrillation (AF) is a major cause of ischemic stroke but may go undetected with short periods of ECG monitoring. The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) demonstrated that long-term electrocardiographic monitoring with insertable cardiac monitors (ICM) is superior to conventional follow-up in detecting AF in the population with cryptogenic stroke. We evaluated the sensitivity and negative predictive value (NPV) of various external monitoring techniques within a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared to continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-hour, 48-hour, and 7-day Holter and 21-day and 30-day event recorders. Periodic monitoring consisted of quarterly monitoring through 24-hour, 48-hour, and 7-day Holters and monthly 24-hour Holters. For a single monitoring period, the sensitivity for AF diagnosis was lowest with a 24-hour Holter (1.3%) and highest with a 30-day event recorder (22.8%). The NPV ranged from 82.3% to 85.6% for all single external monitoring strategies. Quarterly monitoring with 24-hour Holters had a sensitivity of 3.1%, whereas quarterly 7-day monitors increased the sensitivity to 20.8%. The NPVs for repetitive periodic monitoring strategies were similar at 82.6% to 85.3%. Long-term continuous monitoring was superior in detecting AF compared to all intermittent monitoring strategies evaluated (p <0.001). Long-term continuous electrocardiographic monitoring with ICMs is significantly more effective than any of the simulated intermittent monitoring strategies for identifying AF in patients with previous cryptogenic stroke. PMID:26183793

  2. The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression

    PubMed Central

    Xia, Zhen-Biao; Popovic, Relja; Chen, Jing; Theisler, Catherine; Stuart, Tara; Santillan, Donna A.; Erfurth, Frank; Diaz, Manuel O.; Zeleznik-Le, Nancy J.

    2005-01-01

    MLL, involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia, has >50 known partner genes with which it is able to form in-frame fusions. Characterizing important downstream target genes of MLL and of MLL fusion proteins may provide rational therapeutic strategies for the treatment of MLL-associated leukemia. We explored downstream target genes of the most prevalent MLL fusion protein, MLL-AF4. To this end, we developed inducible MLL-AF4 fusion cell lines in different backgrounds. Overexpression of MLL-AF4 does not lead to increased proliferation in either cell line, but rather, cell growth was slowed compared with similar cell lines inducibly expressing truncated MLL. We found that in the MLL-AF4-induced cell lines, the expression of the cyclin-dependent kinase inhibitor gene CDKN1B was dramatically changed at both the RNA and protein (p27kip1) levels. In contrast, the expression levels of CDKN1A (p21) and CDKN2A (p16) were unchanged. To explore whether CDKN1B might be a direct target of MLL and of MLL-AF4, we used chromatin immunoprecipitation (ChIP) assays and luciferase reporter gene assays. MLL-AF4 binds to the CDKN1B promoter in vivo and regulates CDKN1B promoter activity. Further, we confirmed CDKN1B promoter binding by ChIP in MLL-AF4 as well as in MLL-AF9 leukemia cell lines. Our results suggest that CDKN1B is a downstream target of MLL and of MLL-AF4, and that, depending on the background cell type, MLL-AF4 inhibits or activates CDKN1B expression. This finding may have implications in terms of leukemia stem cell resistance to chemotherapy in MLL-AF4 leukemias. PMID:16169901

  3. Validation of the Framingham Heart Study and CHARGE-AF Risk Scores for Atrial Fibrillation in Hispanics, African-Americans, and Non-Hispanic Whites.

    PubMed

    Shulman, Eric; Kargoli, Faraj; Aagaard, Philip; Hoch, Ethan; Di Biase, Luigi; Fisher, John; Gross, Jay; Kim, Soo; Krumerman, Andrew; Ferrick, Kevin J

    2016-01-01

    A risk score for atrial fibrillation (AF) has been developed by the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF consortium. However, validation of these risk scores in an inner-city population is uncertain. Thus, a validation model was built using the Framingham Risk Score for AF and CHARGE-AF covariates. An in and outpatient electrocardiographic database was interrogated from 2000 to 2013 for the development of AF. Patients were included if their age was >45 and <95 years, had <10-year follow-up, if their initial electrocardiogram was without AF, had ≥ 2 electrocardiograms, and declared a race and/or ethnicity as non-Hispanic white, African-American, or Hispanic. For the Framingham Heart Study, 49,599 patients met inclusion criteria, of which 4,860 developed AF. Discrimination analysis using area under the curve (AUC) for original risk equations: non-Hispanic white AUC = 0.712 (95% confidence interval [CI] 0.694 to 0.731), African-American AUC = 0.733 (95% CI 0.716 to 0.751), and Hispanic AUC = 0.740 (95% CI 0.723 to 0.757). For the CHARGE-AF, 45,571 patients met inclusion criteria, of which 4,512 developed AF. Non-Hispanic white AUC = 0.673 (95% CI 0.652 to 0.694), African-American AUC = 0.706 (95% CI 0.685 to 0.727), and Hispanic AUC = 0.711 (95% CI 0.691 to 0.732). Calibration analysis showed qualitative similarities between cohorts. In conclusion, this is the first study to validate both the Framingham Heart Study and CHARGE-AF risk scores in both a Hispanic and African-American cohort. All models predicted AF well across all race and ethnic cohorts. PMID:26589820

  4. Fluorous Polymeric Membranes for Ionophore-Based Ion-Selective Potentiometry: How Inert is Teflon AF?

    PubMed Central

    Lai, Chun-Ze; Koseoglu, Secil S.; Lugert, Elizabeth C.; Boswell, Paul G.; Rábai, József; Lodge, Timothy P.; Bühlmann, Philippe

    2011-01-01

    Fluorous media are the least polar and polarizable condensed phases known. Their use as membrane materials considerably increases the selectivity and robustness of ion-selective electrodes (ISEs). In this research, a fluorous amorphous perfluoropolymer was used for the first time as a matrix for an ISE membrane. Electrodes for pH measurements with membranes composed of poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole]-co-poly(tetrafluoroethylene) (87% dioxole monomer content; known as Teflon AF2400) as polymer matrix, a linear perfluorooligoether as plasticizer, sodium tetrakis[3,5-bis(perfluorohexyl)phenyl]borate providing for ionic sites, and bis[(perfluorooctyl)propyl]-2,2,2-trifluoroethylamine as H+-ionophore were investigated. All electrodes had excellent potentiometric selectivities, showed Nernstian responses to H+ over a wide pH range, exhibited enhanced mechanical stability and maintained their selectivity over at least four weeks. For membranes of low ionophore concentration, the polymer affected the sensor selectivity noticeably at polymer concentrations exceeding 15%. Also, the membrane resistance increased quite strongly at high polymer concentrations, which cannot be explained by the Mackie–Meares obstruction model. The selectivities and resistances depend on the polymer concentration because of a functional group associated with Teflon AF2400, with a concentration of one functional group per 854 monomer units of the polymer. In the fluorous environment of these membranes, this functional group binds to Na+, K+, Ca2+, and the unprotonated ionophore with binding constants of 103.5, 101.8, 106.8 and 104.4 M−1, respectively. Potentiometric and spectroscopic evidence indicates that these functional groups are COOH groups formed by the hydrolysis of carboxylic acid fluoride (COF) groups originally present in Teflon AF2400. The use of higher ionophore concentrations removes the undesirable effect of these COOH groups almost completely

  5. The fraction of breast cancer attributable to smoking: The Norwegian women and cancer study 1991–2012

    PubMed Central

    Gram, Inger T; Little, Melissa A; Lund, Eiliv; Braaten, Tonje

    2016-01-01

    Background: Results from several recent cohort studies on smoking and breast cancer incidence and mortality suggest that the burden of smoking on society is underestimated. We estimated the fraction of breast cancer attributable to smoking in the Norwegian Women and Cancer Study, a nationally representative prospective cohort study. Methods: We followed 130 053 women, aged 34–70 years, who completed a baseline questionnaire between 1991 and 2007, through linkages to national registries through December 2012. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), while adjusting for confounders. Never smokers, excluding passive smokers, were used as the reference group in all main analyses. We estimated attributable fractions (AFs) % in smokers and in the population (PAFs) % with 95% CIs. Results: Altogether, 4293 women developed invasive breast cancer, confirmed by histology. Compared with never active, never passive smokers, ever (former and current) smokers had an overall risk of breast cancer that was 21% higher (HR=1.21; 95% CI=1.08–1.34). For ever smokers, the AF was 17.3% (95% CI =7.4–25.4) and for the population the PAF of breast cancer was 11.9% (95% CI=5.3–18.1). For passive smokers, the PAF of breast cancer was 3.2% (95% CI=1.0–5.4). When we applied PAF estimates for ever smoking on the 2907 new breast cancer cases among Norwegian women aged 35+ at diagnosis in 2012, this yielded 345 (95% CI=154–526) breast cancer cases that could have been avoided in the absence of active smoking that year. Conclusions: In smokers, one in six and in the population, one in nine breast cancer cases could have been avoided in the absence of active smoking. Our findings support the notion that the global cancer burden due to smoking is substantially underestimated. PMID:27280631

  6. Prostate Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Prostate Cancer What is Prostate Cancer? How Tumors Form The body is made up ... the Escape (Esc) button on your keyboard.) How Prostate Cancer Occurs Prostate cancer occurs when a tumor forms ...

  7. Esophageal Cancer

    MedlinePlus

    ... esophagus, and chest wall Lung Cancer Esophageal Cancer Gastroesophageal Reflux Disease Barrett’s Esophagus Chest Wall Tumors Mediastinal Tumors ... Section Navigation Select Topic Lung Cancer Esophageal Cancer Gastroesophageal Reflux Disease Barrett’s Esophagus Chest Wall Tumors Mediastinal Tumors ...

  8. Breast Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Breast Cancer What is Breast Cancer? How Tumors Form The body is made up ... tumors form in the breast tissue. Who Gets Breast Cancer? Breast cancer is one of the most common ...

  9. Testicular cancer

    MedlinePlus

    Cancer - testes; Germ cell tumor; Seminoma testicular cancer; Nonseminoma testicular cancer ... The exact cause of testicular cancer is unknown. Factors that may ... increases if he has: Abnormal testicle development Exposure ...

  10. Breast Cancer

    MedlinePlus

    Breast cancer affects one in eight women during their lives. Breast cancer kills more women in the United States ... cancer. No one knows why some women get breast cancer, but there are a number of risk ...

  11. Ovarian Cancer

    MedlinePlus

    Ovarian Cancer There are five main types of cancer that affect a woman’s reproductive organs: cervical, ovarian, uterine, ... rare fallopian tube cancer.) This fact sheet about ovarian cancer is part of the Centers for Disease Control ...

  12. Cancer Statistics

    MedlinePlus

    ... cancer statistics across the world. U.S. Cancer Mortality Trends The best indicator of progress against cancer is ... the number of cancer survivors has increased. These trends show that progress is being made against the ...

  13. Breast cancer

    MedlinePlus

    ... of targeted therapy. It blocks certain hormones that fuel cancer growth. Cancer treatment can be local or ... breast cancer should not drink alcohol at all) Alternative Names Cancer - breast; Carcinoma - ductal; Carcinoma - lobular; DCIS; ...

  14. Fusagerins A-F, New Alkaloids from the Fungus Fusarium sp.

    PubMed

    Wen, Hao; Li, Yan; Liu, Xingzhong; Ye, Wencai; Yao, Xinsheng; Che, Yongsheng

    2015-08-01

    Fusagerins A-F (1-6), six new alkaloids including a unique one with the rare a-(N-formyl)carboxamide moiety (1), a hydantoin (imidazolidin-2,4-dione) derivative (2), and four fungerin analogues (3-6), were isolated from the crude extract of the fungus Fusarium sp., together with the known compound fungerin (7). Compound 2 was isolated as a racemate and further separated into two enantiomers on a chiral HPLC column. The structures of 1-6 were determined mainly by NMR experiments, and the absolute configuration of 1 and 2 was assigned by electronic circular dichroism (ECD) calculations. Compound 7 showed antibacterial activity against Staphylococcus aureus and Streptococcus pneumoniae, and weak cytotoxicity against the T24 cells. PMID:26329590

  15. RNA structure replaces the need for U2AF2 in splicing

    PubMed Central

    Lin, Chien-Ling; Taggart, Allison J.; Lim, Kian Huat; Cygan, Kamil J.; Ferraris, Luciana; Creton, Robbert; Huang, Yen-Tsung; Fairbrother, William G.

    2016-01-01

    RNA secondary structure plays an integral role in catalytic, ribosomal, small nuclear, micro, and transfer RNAs. Discovering a prevalent role for secondary structure in pre-mRNAs has proven more elusive. By utilizing a variety of computational and biochemical approaches, we present evidence for a class of nuclear introns that relies upon secondary structure for correct splicing. These introns are defined by simple repeat expansions of complementary AC and GT dimers that co-occur at opposite boundaries of an intron to form a bridging structure that enforces correct splice site pairing. Remarkably, this class of introns does not require U2AF2, a core component of the spliceosome, for its processing. Phylogenetic analysis suggests that this mechanism was present in the ancestral vertebrate lineage prior to the divergence of tetrapods from teleosts. While largely lost from land dwelling vertebrates, this class of introns is found in 10% of all zebrafish genes. PMID:26566657

  16. AF-GEOSpace Version 2.0: Space Environment Software Products for 2002

    NASA Astrophysics Data System (ADS)

    Hilmer, R. V.; Ginet, G. P.; Hall, T.; Holeman, E.; Tautz, M.

    2002-05-01

    AF-GEOSpace Version 2.0 (release 2002 on WindowsNT/2000/XP) is a graphics-intensive software program developed by AFRL with space environment models and applications. It has grown steadily to become a development tool for automated space weather visualization products and helps with a variety of tasks: orbit specification for radiation hazard avoidance; satellite design assessment and post-event analysis; solar disturbance effects forecasting; frequency and antenna management for radar and HF communications; determination of link outage regions for active ionospheric conditions; and physics research and education. The object-oriented C++ code is divided into five module classes. Science Modules control science models to give output data on user-specified grids. Application Modules manipulate these data and provide orbit generation and magnetic field line tracing capabilities. Data Modules read and assist with the analysis of user-generated data sets. Graphics Modules enable the display of features such as plane slices, magnetic field lines, line plots, axes, the Earth, stars, and satellites. Worksheet Modules provide commonly requested coordinate transformations and calendar conversion tools. Common input data archive sets, application modules, and 1-, 2-, and 3-D visualization tools are provided to all models. The code documentation includes detailed examples with click-by-click instructions for investigating phenomena that have well known effects on communications and spacecraft systems. AF-GEOSpace Version 2.0 builds on the success of its predecessors. The first release (Version 1.21, 1996/IRIX on SGI) contained radiation belt particle flux and dose models derived from CRRES satellite data, an aurora model, an ionosphere model, and ionospheric HF ray tracing capabilities. Next (Version 1.4, 1999/IRIX on SGI) science modules were added related to cosmic rays and solar protons, low-Earth orbit radiation dosages, single event effects probability maps, ionospheric

  17. Fatigue life estimation program for Part 23 airplanes, `AFS.FOR`

    SciTech Connect

    Kaul, S.K.

    1993-12-31

    The purpose of this paper is to introduce to the general aviation industry a computer program which estimates the safe fatigue life of any Federal Aviation Regulation (FAR) Part 23 airplane. The algorithm uses the methodology (Miner`s Linear Cumulative Damage Theory) and the various data presented in the Federal Aviation Administration (FAA) Report No. AFS-120-73-2, dated May 1973. The program is written in FORTRAN 77 language and is executable on a desk top personal computer. The program prompts the user for the input data needed and provides a variety of options for its intended use. The program is envisaged to be released through issuance of a FAA report, which will contain the appropriate comments, instructions, warnings and limitations.

  18. Hypocriols A-F, Heterodimeric Botryane Ethers from Hypocrea sp., an Insect-Associated Fungus.

    PubMed

    Ren, Fengxia; Zhu, Shuaiming; Wang, Bo; Li, Li; Liu, Xingzhong; Su, Ruibin; Che, Yongsheng

    2016-07-22

    The new heterodimeric botryane ethers hypocriols A-F (1-6) and the known compounds 4β-acetoxy-9β,10β,15α-trihydroxyprobotrydial (7), dihydrobotrydial (8), 10-oxodehydrodihydrobotrydial (9), and dehydrobotrydienol (10) were isolated from the solid cultures of an insect-associated fungus Hypocrea sp. The structures of 1-6 were elucidated primarily by NMR experiments. The absolute configuration of 1 was assigned using the modified Mosher method and electronic circular dichroism (ECD) calculations, whereas those for 3-5, and 2 and 6 were deduced via ECD calculations and circular dichroism data, respectively. Compounds 1-6 appear to be the first heterodimeric botryane ethers and showed antiproliferative effects against a small panel of four human tumor cell lines. PMID:27328173

  19. Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

    PubMed

    Zhou, Wen-Bing; Zeng, Guang-Zhi; Xu, Hui-Min; He, Wen-Jun; Zhang, Yu-Mei; Tan, Ning-Hua

    2014-03-01

    Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 μM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 μM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 μM. PMID:24393620

  20. Hot-Fire Testing of a 1N AF-M315E Thruster

    NASA Technical Reports Server (NTRS)

    Burnside, Christopher G.; Pedersen, Kevin; Pierce, Charles W.

    2015-01-01

    This hot-fire test continues NASA investigation of green propellant technologies for future missions. To show the potential for green propellants to replace some hydrazine systems in future spacecraft, NASA Marshall Space Flight Center (MSFC) is continuing to embark on hot-fire test campaigns with various green propellant blends. NASA completed a hot-fire test of a 1N AF-M315E monopropellant thruster at the Marshall Space Flight Center in the small altitude test stand located in building 4205. The thruster is a ground test article used for basic performance determination and catalyst studies. The purpose of the hot-fire testing was for performance determination of a 1N size thruster and form a baseline from which to study catalyst performance and life with follow-on testing to be conducted at a later date. The thruster performed as expected. The result of the hot-fire testing are presented in this paper and presentation.

  1. AF printability check with a full-chip 3D resist profile model

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-En R.; Chang, Jason; Song, Hua; Shiely, James

    2013-09-01

    A single compact resist model capable of predicting 3D resist profile is strongly demanded for the advanced technology nodes to avoid the potential hotspots due to imperfect resist pattern shape and its lack of resistance in the subsequent etch process. In this work, we propose a resist 3D (R3D) compact model that takes acidz-diffusion effect into account. The chemical reaction between acid and base along z-direction is treated as second order effect that is absorbed into the anisotropic diffusion length as a fitting parameter. Meanwhile, the resist model in the x-y wafer plane is still kept in general by applying the compact solution of 2D reaction-diffusion equation. In order to have the 2D contour predictability at arbitrary resist height, calibration from entire 3D data (CDs at several heights) areconducted simultaneously witha single cost function so that the R3D compact model is described by a common set of resist free parameters and threshold for all resist heights. With the low energy approximation, the acid z-diffusion effect is equivalent to a z-diffused TCC that takes the form of linear combination of pure optical TCCs sampled at discrete image-depth which can be pre-calculated. With this benefit, the R3D compact model offers a more physical approach but adds no runtime concern on the OPC and verification applications. The predicted resist cross-section profiles from our test patterns are compared those computed with rigorous lithography simulator SLITHO and show very good matching results between them. The demonstration of the AF printability check from the predicted cross-section profile at AF indicates the success of our R3D compact model.

  2. Roles of two-component system AfsQ1/Q2 in regulating biosynthesis of the yellow-pigmented coelimycin P2 in Streptomyces coelicolor.

    PubMed

    Chen, Shuangshuang; Zheng, Guosong; Zhu, Hong; He, Huiqi; Chen, Lei; Zhang, Weiwen; Jiang, Weihong; Lu, Yinhua

    2016-08-01

    We previously demonstrated that in Streptomyces coelicolor two-component system AfsQ1/Q2 activates the production of the yellow-colored coelimycin P2 (also named as yCPK) on glutamate-supplemented minimal medium, and the response regulator AfsQ1 could specifically bind to the intergenic region between two structural genes, cpkA and cpkD Here, a more in-depth investigation was performed to elucidate the mechanism underlying the role of AfsQ1/Q2 in regulating coelimycin P2 biosynthesis. Deletion of afsQ1/Q2 resulted in markedly decreased expression of the whole coelimycin P2 biosynthetic gene cluster. Electrophoretic mobility shift assays revealed that AfsQ1 bound only to the target site identified previously, but not to any other promoters in the gene cluster. Mutations of AfsQ1-binding motif only resulted in drastically reduced transcription of the cpkA/B/C operon (encoding three type I polyketide synthases) and intriguingly, led to enhanced expression of some coelimcyin P2 genes, particularly accA1 and scF These results suggested the direct role of AfsQ1/Q2 in regulating coelimycin production, which is directly mediated by the structural genes, but not the cluster-situated regulatory genes, and also implied that other unknown mechanisms may be involved in AfsQ1/Q2-mediated regulation of coelimycin P2 biosynthesis. PMID:27313101

  3. 75 FR 9596 - Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-03

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Notice of Filing of a Pesticide Petition for Residues of a Aspergillus flavus AF36 on Corn Food... residues of the antifungal ] agent, Aspergillus flavus AF36, in or on corn food and feed commodities....

  4. Clone-derived human AF-amniotic fluid stem cells are capable of skeletal myogenic differentiation in vitro and in vivo.

    PubMed

    Ma, Xiaorong; Zhang, Shengli; Zhou, Junmei; Chen, Baisong; Shang, Yafeng; Gao, Tongbing; Wang, Xue; Xie, Hua; Chen, Fang

    2012-08-01

    Stem cell-based therapy may be the most promising method to cure skeletal muscle degenerative diseases such as Duchenne muscular dystrophy (DMD) and trauma in the future. Human amniotic fluid is enriched with early-stage stem cells from developing fetuses and these cells have cardiomyogenic potential both in vitro and in vivo. In the present study, we investigated the characteristics of human amniotic fluid-derived AF-type stem (HAF-AFS) cells by flow cytometry, immunofluorescence staining, reverse-transcription polymerase chain reaction, and osteogenic and adipogenic differentiation analysis. After confirming the stemness of HAF-AFS cells, we tested whether HAF-AFS cells could differentiate into skeletal myogenic cells in vitro and incorporate into regenerating skeletal muscle in vivo. By temporary exposure to the DNA demethylation agent 5-aza-2'-deoxycytidine (5-Aza dC) or co-cultured with C2C12 myoblasts, HAF-AFS cells differentiated into skeletal myogenic cells, expressing skeletal myogenic cell-specific markers such as Desmin, Troponin I (Tn I) and α-Actinin. Four weeks after transplantation into cardiotoxin-injured and X-ray-irradiated tibialis anterior (TA) muscles of NOD/SCID mice, HAF-AFS cells survived, differentiated into myogenic precursor cells and fused with host myofibres. The findings that HAF-AFS cells differentiate into myogenic cells in vitro and incorporate in skeletal muscle regeneration in vivo hold the promise of HAF-AFS cell-based therapy for skeletal muscle degenerative diseases. PMID:22396316

  5. Evaluation of the Sustainability and Clinical Outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) in a Child Protection Center

    ERIC Educational Resources Information Center

    Kolko, David J.; Iselin, Anne-Marie R.; Gully, Kevin J.

    2011-01-01

    This paper examines the sustainability and outcome of Alternatives for Families: A Cognitive-Behavioral Therapy (AF-CBT) as delivered by practitioners in a community-based child protection program who had received training in the model several years earlier. Formerly described as Abuse-Focused CBT, AF-CBT is an evidence-based treatment (EBT) for…

  6. Lung cancer

    SciTech Connect

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer.

  7. Characterization of extractable soil organic matter pools from African Dark Earths (AfDE): A case study in historical biochar and organic waste amendments

    NASA Astrophysics Data System (ADS)

    Fujiu, Manna; Plante, Alain; Ohno, Tsutomu; Solomon, Dawit; Lehmann, Johannes; Fraser, James; Leach, Melissa; Fairhead, James

    2014-05-01

    Anthropogenic Dark Earths are soils generated through long-term human inputs of organic and pyrogenic materials. These soils were originally discovered in the Amazon, and have since been found in Australia and in this case in Africa. African Dark Earths (AfDE) are black, highly fertile and carbon-rich soils that were formed from the original highly-weathered infertile yellowish to red Oxisols and Ultisols through an extant but hitherto overlooked climate-smart sustainable soil management system that has long been an important feature of the indigenous West African agricultural repertoire. Studies have demonstrated that ADE soils in general have significantly different organic matter properties compared to adjacent non-DE soils, largely attributable to the presence of high concentrations of ash-derived carbon. Quantification and characterization of bulk soil organic matter of several (n=11) AfDE and non-AfDE pairs of surface (0-15 cm) soils using thermal analysis techniques (TG-DSC-EGA) confirmed substantial differences in SOM composition and the presence of pyrogenic C. Such pyrogenic organic matter is generally considered recalcitrant or relatively stable, but the goal of the current study was to characterize the presumably labile, more rapidly cycling, pools of C in AfDEs through the characterization of hot water- and pyrophosphate-extractable fractions, referred to as HWEOC and PyroC respectively. Extracts were analyzed for carbon content, as well as composition using fluorescence (EEM/PARAFAC) and high resolution mass spectrometry (FTICR-MS). The amount of extractable C as a proportion of total soil C was relatively low: less than ~0.8% for HWEOC and 2.8% for PyroC. The proportion of HWEOC did not differ (P = 0.18, paired t-test) between the AfDE and the non-AfDE soils, while the proportions of PyroC were significantly larger (P = 0.001) in the AfDE soils compared to the non-AfDE soils. Preliminary analysis of the EEM/PARAFAC data suggests that AfDE samples had

  8. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents For ... for Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next ...

  9. 6 Common Cancers - Skin Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  10. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents For ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next ...

  11. Verbesinosides A-F, Novel 15,27-Cyclooleanane Saponins from the American Native Plant Verbesina virginica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Verbesinosides A-F (1-6), six novel 15,27-cyclooleanane-type triterpenoid saponins carrying different aromatic acyl moieties on the aglycone, were isolated from the leaf and flower of Verbesina virginica. Their structures were established by interpretation of spectroscopic data and chemical methods....

  12. The Implementation of Collaborative Learning Using AfL through Giving Feedback Strategy for Improving Students’ Attention to Mathematics Lesson

    NASA Astrophysics Data System (ADS)

    Kurniasih, R.; Sujadi, I.; Pramesti, G.

    2016-02-01

    This research aims to describe the process of implementation collaborative learning with AfL through giving feedback strategy for improving students’ attention to mathematics lesson. Data which is collected in this research are students’ attention towards learning and students’ achievement. The result of this research showed that the learning steps by using collaborative learning with AfL through giving feedback strategy which can improve students’ attention are: 1) pre activity: the teacher delivers the purpose of the learning, successful criteria, apperception, and motivation. 2) main activity: the teacher gives the background of learning activity, explains learning materials at a glance, divides students discuss, the teacher observes and guides students to the problem solving, present their discussion result, gives feedback, the students do AfL problem and the answer is collected and result will be given before next meeting. 3) post activity: the teacher with students concludes the material. Test result, the percentage of students who complete the examination in the second cycle is 77.27%. Based on those results can be concluded that the implementation of collaborative learning using AfL through giving feedback can improve students’ attention towards learning and students’ achievement of XI IPA Students MA Al-Islam Jamsaren Surakarta academic year 2013/2014.

  13. Determining Aqueous Fullerene Particle Size Distributions by Asymmetric Flow Field-Flow Fractionation (AF4) without Surfactants

    EPA Science Inventory

    To determine the behavior of nanoparticles in environmental systems, methods must be developed to measure nanoparticle size. Asymmetric Flow Field Flow Fractionation (AF4) is an aqueous compatible size separation technique which is able to separate particles from 1 nm to 10 µm in...

  14. Ultrasound body composition traits response to an endotoxin challenge in Brahman heifers supplemented with Omnigen-AF

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study examined the effect of feeding OmniGen-AF (OG; Prince Agri Products) on the body composition traits response of newly-weaned heifers to an endotoxin (lipopolysaccharide; LPS) challenge. Brahman heifers (n=24; 183 ± 5 kg) from the Texas AgriLife Research Center in Overton, TX, were separat...

  15. Reworking Practice through an AfL Project: An Analysis of Teachers' Collaborative Engagement with New Assessment Guidelines

    ERIC Educational Resources Information Center

    Hermansen, Hege; Nerland, Monika

    2014-01-01

    In recent years, the concept of Assessment for Learning (AfL) has travelled across countries, giving rise to a range of educational policy initiatives and school development projects. While researchers have focused on issues such as how formative assessment can support student learning and lead to more efficient classroom practices, less attention…

  16. What Causes Cancer?

    MedlinePlus

    ... articles window. My Saved Articles » My ACS » What Causes Cancer? Cancer is a complex group of diseases with ... cancer. Learn About Cancer Topics Cancer Basics What Causes Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate ...

  17. Immunoscore in Rectal Cancer

    ClinicalTrials.gov

    2016-03-28

    Cancer of the Rectum; Neoplasms, Rectal; Rectal Cancer; Rectal Tumors; Rectal Adenocarcinoma; Melanoma; Breast Cancer; Renal Cell Cancer; Lung Cancer; Bladder Cancer; Head and Neck Cancer; Ovarian Cancer; Thyroid Cancer

  18. Phosphorylation of the AfsR product, a global regulatory protein for secondary-metabolite formation in Streptomyces coelicolor A3(2).

    PubMed Central

    Hong, S K; Kito, M; Beppu, T; Horinouchi, S

    1991-01-01

    The AfsR protein is essential for the biosynthesis at the wild-type level of A-factor, actinorhodin, and undecylprodigiosin in Streptomyces coelicolor A3(2) and Streptomyces lividans. Because overexpression of the afsR gene caused some deleterious effect on these strains, a multicopy plasmid carrying the whole afsR gene was introduced into Streptomyces griseus, from which a crude cell lysate was prepared as a protein source. The AfsR protein was purified to homogeneity from the cytoplasmic fraction through several steps of chromatography, including affinity column chromatography with ATP-agarose and use of anti-AfsR antibody for its detection. The molecular weight of AfsR was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by gel filtration to be 105,300, which is in good agreement with that deduced from the nucleotide sequence of afsR. The purified AfsR protein was found to be phosphorylated through the transfer of the gamma-phosphate group of ATP in the presence of the cell extracts of S. coelicolor A3(2) and S. lividans. This phosphorylation proceeded very rapidly, and no competition was observed with CTP, GTP, UTP, or cyclic AMP. In the cell extract of S. griseus, no activity phosphorylating the AfsR protein was detected, suggesting that this activity is not generally present in Streptomyces spp. but is specific to certain species. It is conceivable that the extent of phosphorylation of the AfsR protein modulates its regulatory activity which, in turn, regulates expression of some target gene(s) involved in the secondary-metabolite formation in S. coelicolor A3(2). Images PMID:2007554

  19. Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

    PubMed

    Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

    2012-08-01

    An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications. PMID:22197801

  20. Unraveling the Activation Mechanism of Taspase1 which Controls the Oncogenic AF4–MLL Fusion Protein

    PubMed Central

    Sabiani, Samaneh; Geppert, Tim; Engelbrecht, Christian; Kowarz, Eric; Schneider, Gisbert; Marschalek, Rolf

    2015-01-01

    We have recently demonstrated that Taspase1-mediated cleavage of the AF4–MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4–MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4–MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4–MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4–MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed. PMID:26137584

  1. High morbidity in myocardial infarction and heart failure patients after gastric cancer surgery

    PubMed Central

    Jeong, Sang-Ho; Kim, Young-Woo; Yu, Wansik; Lee, Sang Ho; Park, Young Kyu; Park, Seong-Heum; Jeong, In Ho; Lee, Sang Eok; Park, Yongwhi; Lee, Young-Joon

    2015-01-01

    AIM: To evaluate to morbidity and mortality differences between 4 underlying heart diseases, myocardial infarction (MI), angina pectoris (Angina), heart failure (HF), and atrial fibrillation (AF), after radical surgery for gastric cancer. METHODS: We retrospectively collected data from 221 patients of a total of 15167 patients who underwent radical gastrectomy and were preoperatively diagnosed with a history of Angina, MI, HF, or AF in 8 hospitals. RESULTS: We find that the total morbidity rate is significantly higher in the MI group (44%) than the Angina (15.7%), AF (18.8%), and HF (23.1%) groups (P < 0.01). Moreover, we note that the risk for postoperative cardiac problems is higher in patients with a history of HF (23.1%) than patients with a history of Angina (2.2%), AF (4.3%), or MI (6%; P = 0.01). The HF and MI groups each have 1 case of cardiogenic mortality. CONCLUSION: We conclude that MI patients have a higher risk of morbidity, and HF patients have a higher risk of postoperative cardiac problems than Angina or AF. PMID:26074701

  2. Quality of Life in Patients Undergoing Radiation Therapy for Primary Lung Cancer, Head and Neck Cancer, or Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer; Small Intestine Cancer

  3. Doppler images and the underlying dynamo. The case of AF Leporis

    NASA Astrophysics Data System (ADS)

    Järvinen, S. P.; Arlt, R.; Hackman, T.; Marsden, S. C.; Küker, M.; Ilyin, I. V.; Berdyugina, S. V.; Strassmeier, K. G.; Waite, I. A.

    2015-02-01

    Context. The (Zeeman-)Doppler imaging studies of solar-type stars very often reveal large high-latitude spots. This also includes F stars that possess relatively shallow convection zones, indicating that the dynamo operating in these stars differs from the solar dynamo. Aims: We aim to determine whether mean-field dynamo models of late-F type dwarf stars can reproduce the surface features recovered in Doppler maps. In particular, we wish to test whether the models can reproduce the high-latitude spots observed on some F dwarfs. Methods: The photometric inversions and the surface temperature maps of AF Lep were obtained using the Occamian-approach inversion technique. Low signal-to-noise spectroscopic data were improved by applying the least-squares deconvolution method. The locations of strong magnetic flux in the stellar tachocline as well as the surface fields obtained from mean-field dynamo solutions were compared with the observed surface temperature maps. Results: The photometric record of AF Lep reveals both long- and short-term variability. However, the current data set is too short for cycle-length estimates. From the photometry, we have determined the rotation period of the star to be 0.9660 ± 0.0023 days. The surface temperature maps show a dominant, but evolving, high-latitude (around +65°) spot. Detailed study of the photometry reveals that sometimes the spot coverage varies only marginally over a long time, and at other times it varies rapidly. Of a suite of dynamo models, the model with a radiative interior rotating as fast as the convection zone at the equator delivered the highest compatibility with the obtained Doppler images. Partially based on observations made with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofísica de Canarias.Based partly on STELLA SES data.Tables 1-3 and Figs. 7-14 are available in

  4. Antisecretory Factor Peptide AF-16 Inhibits the Secreted Autotransporter Toxin-Stimulated Transcellular and Paracellular Passages of Fluid in Cultured Human Enterocyte-Like Cells

    PubMed Central

    Nicolas, Valérie

    2014-01-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of d-[1-14C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  5. Antisecretory factor peptide AF-16 inhibits the secreted autotransporter toxin-stimulated transcellular and paracellular passages of fluid in cultured human enterocyte-like cells.

    PubMed

    Nicolas, Valérie; Liévin-Le Moal, Vanessa

    2015-03-01

    Both the endogenous antisecretory factor (AF) protein and peptide AF-16, which has a sequence that matches that of the active N-terminal region of AF, inhibit the increase in the epithelial transport of fluid and electrolytes induced by bacterial toxins in animal and ex vivo models. We conducted a study to investigate the inhibitory effect of peptide AF-16 against the increase of transcellular passage and paracellular permeability promoted by the secreted autotransporter toxin (Sat) in a cultured cellular model of the human intestinal epithelial barrier. Peptide AF-16 produced a concentration-dependent inhibition of the Sat-induced increase in the formation of fluid domes, in the mucosal-to-serosal passage of D-[1-(14)C]mannitol, and in the rearrangements in the distribution and protein expression of the tight junction (TJ)-associated proteins ZO-1 and occludin in cultured human enterocyte-like Caco-2/TC7 cell monolayers. In addition, we show that peptide AF-16 also inhibits the cholera toxin-induced increase of transcellular passage and the Clostridium difficile toxin-induced effects on paracellular permeability and TJ protein organization in Caco-2/TC7 cell monolayers. Treatment of cell monolayers by the lipid raft disorganizer methyl-β-cyclodextrin abolished the inhibitory activity of peptide AF-16 at the transcellular passage level and did not modify the effect of the peptide at the paracellular level. PMID:25534938

  6. U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs.

    PubMed

    Jenkins, Jermaine L; Agrawal, Anant A; Gupta, Ankit; Green, Michael R; Kielkopf, Clara L

    2013-04-01

    Degenerate splice site sequences mark the intron boundaries of pre-mRNA transcripts in multicellular eukaryotes. The essential pre-mRNA splicing factor U2AF(65) is faced with the paradoxical tasks of accurately targeting polypyrimidine (Py) tracts preceding 3' splice sites while adapting to both cytidine and uridine nucleotides with nearly equivalent frequencies. To understand how U2AF(65) recognizes degenerate Py tracts, we determined six crystal structures of human U2AF(65) bound to cytidine-containing Py tracts. As deoxy-ribose backbones were required for co-crystallization with these Py tracts, we also determined two baseline structures of U2AF(65) bound to the deoxy-uridine counterparts and compared the original, RNA-bound structure. Local structural changes suggest that the N-terminal RNA recognition motif 1 (RRM1) is more promiscuous for cytosine-containing Py tracts than the C-terminal RRM2. These structural differences between the RRMs were reinforced by the specificities of wild-type and site-directed mutant U2AF(65) for region-dependent cytosine- and uracil-containing RNA sites. Small-angle X-ray scattering analyses further demonstrated that Py tract variations select distinct inter-RRM spacings from a pre-existing ensemble of U2AF(65) conformations. Our results highlight both local and global conformational selection as a means for universal 3' splice site recognition by U2AF(65). PMID:23376934

  7. Dot1a-AF9 Complex Mediates Histone H3 Lys-79 Hypermethylation and Repression of ENaCα in an Aldosterone-sensitive Manner*

    PubMed Central

    Zhang, Wenzheng; Xia, Xuefeng; Reisenauer, Mary Rose; Hemenway, Charles S.; Kone, Bruce C.

    2010-01-01

    Aldosterone is a major regulator of epithelial Na+ absorption and acts in large part through induction of the epithelial Na+ channel (ENaC) gene in the renal collecting duct. We previously identified Dot1a as an aldosterone early repressed gene and a repressor of ENaCα transcription through mediating histone H3 Lys-79 methylation associated with the ENaCα promoter. Here, we report a novel aldosterone-signaling network involving AF9, Dot1a, and ENaCα. AF9 and Dot1a interact in vitro and in vivo as evidenced in multiple assays and colocalize in the nuclei of mIMCD3 renal collecting duct cells. Overexpression of AF9 results in hypermethylation of histone H3 Lys-79 at the endogenous ENaCα promoter at most, but not all subregions examined, repression of endogenous ENaCα mRNA expression and acts synergistically with Dot1a to inhibit ENaCα promoter-luciferase constructs. In contrast, RNA interference-mediated knockdown of AF9 causes the opposite effects. Chromatin immunoprecipitation assays reveal that overexpressed FLAG-AF9, endogenous AF9, and Dot1a are each associated with the ENaCα promoter. Aldosterone negatively regulates AF9 expression at both mRNA and protein levels. Thus, Dot1a-AF9 modulates histone H3 Lys-79 methylation at the ENaCα promoter and represses ENaCα transcription in an aldosterone-sensitive manner. This mechanism appears to be more broadly applicable to other aldosterone-regulated genes because overexpression of AF9 alone or in combination with Dot1a inhibited mRNA levels of three other known aldosterone-inducible genes in mIMCD3 cells. PMID:16636056

  8. Aerodigestive cancers: oral cancer.

    PubMed

    Haws, Luke; Haws, Bryn Taylor

    2014-09-01

    Worldwide, approximately 260,000 new cases of oral cancer occur, and more than 125,000 mortalities are attributed to oral cancers each year. Oral cancers most commonly arise in the tongue, followed by the floor of the mouth and the lower gum. Tobacco and alcohol use are the major risk factors, although human papillomavirus has been identified as an etiology in a small percentage of oral squamous cell cancers. Although the evidence to support routine annual screening for oral cancers is inconclusive, family physicians and dental practitioners should be attentive to precursor lesions, such as leukoplakia and erythroplakia, and strongly consider obtaining or referring for biopsy patients with suspicious lesions. Depending on stage, management of oral cancers often involves surgery, with or without postoperative radiotherapy or chemotherapy. Patients who have been treated for these cancers should undergo close surveillance by otolaryngology subspecialists, but their family physicians primarily will be responsible for their long-term care. Complications relating to management, including difficulties with speech, swallowing, and chewing, will need to be addressed. For patients with advanced-stage disease, family physicians also may be responsible for palliative and end-of-life care. PMID:25198382

  9. Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.

    PubMed

    Lowres, Nicole; Neubeck, Lis; Salkeld, Glenn; Krass, Ines; McLachlan, Andrew J; Redfern, Julie; Bennett, Alexandra A; Briffa, Tom; Bauman, Adrian; Martinez, Carlos; Wallenhorst, Christopher; Lau, Jerrett K; Brieger, David B; Sy, Raymond W; Freedman, S Ben

    2014-06-01

    Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ≥65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ≥2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered. PMID:24687081

  10. Perturbative magnetoresistance technique used to investigate FM/AF coupled bilayers

    NASA Astrophysics Data System (ADS)

    Oliveira, Alexandre; da Costa, Ricardo; Melo, Abner; Chesman, Carlos

    2014-03-01

    In this study we introduced modifications to a collinear four probe magnetoresistance set-up in order to measure magnetic properties that can only be sensed by techniques based on magnetization perturbation. In addition to the applied DC magnetic field (Hdc) , in magnetoresistance experiments, a small and quasi-static alternating magnetic field (hac, less than 10 Oe and around 800 Hz) is applied perpendicularly, both parallel to the sample plane. Due to Zeeman interaction, hac drives sample magnetization to oscillate slightly around its equilibrium position. Although we apply only DC current (few mA), the detected voltage carries DC and AC components. The DC voltage component provides information on magnetoresistance (MR) and the AC component is called perturbative magnetoresistance (PMR). We successfully demonstrated that the PMR signal is proportional to the first derivative of resistance with respect to hac. Using this technique and a phenomenological model that takes into account the relevant free energy terms of FM/AF coupled bilayers, we were able to study reversible and irreversible magnetization rotation processes in these magnetic systems. With respect to magnetic anisotropy, we investigated rotatable anisotropy, proposed by McMichael et al and Geshev et al. Financial support: CNPq, FAPERN and CAPES (Brazilian agencies).

  11. Bisphenol AF may cause testosterone reduction by directly affecting testis function in adult male rats.

    PubMed

    Feng, Yixing; Yin, Jie; Jiao, Zhihao; Shi, Jiachen; Li, Ming; Shao, Bing

    2012-06-01

    Although in vitro studies have indicated that Bisphenol AF (BPAF) might be a more dangerous endocrine disruptor than Bisphenol A (BPA), no information on reproductive toxicity in animals is available. In this study, the effects of BPAF exposure on the testis and the related mechanisms of toxicity were investigated. Sprague-Dawley (SD) male rats were exposed to BPAF (0, 2, 10, 50 and 200 mg/kg/d) for 14 days. Total cholesterol levels in serum were decreased in rats given a dose of 50 and 200 mg/kg/d. BPAF concentration in the testes increased with increasing doses of BPAF. Reduced serum testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were observed in rats in the higher dose groups. Furthermore, BPAF exposure resulted in a dramatic decline in genes and protein involved in cholesterol biosynthesis, transport and steroid biosynthesis. Similarly, the testicular mRNA levels of inhibin B, estrogen receptor (ERα) and luteinizing hormone receptor (LHR) also decreased in rats given a dosage of 200 mg/kg/d BPAF. Together, these data demonstrate that BPAF-induced inhibition of testosterone production primarily resulted from the alteration of genes and proteins in the testosterone biosynthesis pathway. PMID:22504055

  12. Neurotoxic effects of bisphenol AF on calcium-induced ROS and MAPKs.

    PubMed

    Lee, Soyoung; Kim, Yoo Kyeong; Shin, Tae-Yong; Kim, Sang-Hyun

    2013-04-01

    Bisphenol AF (BPAF), a newly introduced chemical structurally related to bisphenol A, is used extensively in fluoroelastomers and polyesters, and has been known to induce estrogen-dependent responses. However, the toxicity of BPAF is largely unknown except for its endocrine-related effects. In this study, we investigated the neurotoxicity of BPAF and underlying mechanisms of action using hippocampal cell line (HT-22) and mouse primary neuronal cells. We found that BPAF induced apoptosis in both HT-22 and primary neuronal cells. In order to clarify the underlying mechanisms of BPAF-induced apoptosis, various signaling molecules were evaluated. BPAF increased the level of intracellular calcium, followed by the generation of reactive oxygen species (ROS). BPAF upregulated the phosphorylation of mitogen-activated protein kinase: extracellular signal-regulated kinase, p38 and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor-κB. Using specific inhibitors, we confirmed that calcium, ROS, p38, and JNK mediated the BPAF-induced apoptosis. In addition, BPAF inhibited microglial activation in a microglia/neuroblastoma coculture model by the reduction of nitric oxide production. We found that BPAF interrupted the normal physiologic functions of microglia at non-toxic levels. Taken together, our results suggest that BPAF, the substitute of BPA, also have neurotoxic properties. PMID:22996013

  13. Detection of a Light Echo from the Otherwise Normal SN 2007af

    NASA Astrophysics Data System (ADS)

    Drozdov, D.; Leising, M. D.; Milne, P. A.; Pearcy, J.; Riess, A. G.; Macri, L. M.; Bryngelson, G. L.; Garnavich, P. M.

    2015-05-01

    We present the discovery of a light echo from SN 2007af, a normal Type Ia supernova (SN Ia) in NGC 5584. Hubble Space Telescope images taken three years post explosion reveal two separate echoes: an outer echo and an extended central region, which we propose to be an inner echo for which details are unresolved. Multiple images were obtained in the F160W, F350LP, F555W, and F814W using the Wide Field Camera 3. If the outer echo is produced by an interstellar dust sheet perpendicular to the line of sight, it is located ∼800 pc in front of the SN. The dust for the inner echo is 0.45 pc \\lt d\\lt 90 pc away from the SN. The inner echo color is consistent with typical interstellar dust wavelength-dependent scattering cross-sections, while the outer echo is redder than predicted. Both dust sheets, if in the foreground, are optically thin for scattering, and the outer echo sheet thickness is consistent with the inferred extinction from peak brightness. Whether the inner echo is from interstellar or circumstellar dust is ambiguous. Overall, the echo characteristics are quite similar to previously observed SN Ia echoes.

  14. Chemically peculiar A/F stars in open clusters of the Milky Way

    NASA Astrophysics Data System (ADS)

    Gebran, M.; Monier, R.

    2010-12-01

    Abundance anomalies have been determined at the surface of many field and open cluster A and F dwarfs. These abundance anomalies are most likely caused by microscopic diffusion at work within the stable envelopes of A stars. However diffusion can be counteracted by several other mixing processes such as convection, rotational mixing and mass loss. We present a short review of the surface abundance patterns of A/F stars in the Pleiades (100 Myr), Coma Berenices (450 Myr) and Hyades (650 Myr) open clusters. Real star-to-star variations of the abundances were found for several chemical elements in the A dwarfs in these clusters. The derived abundances are then compared to evolutionary models from the Montreal group. These comparisons strongly suggest the occurence of hydrodynamical processes at play within the radiative zones of these stars and hindering the effects of microscopic diffusion (mixing processes/mass loss). In the frame of Gaia mission, simulations are presented that predict the number of A stars and open clusters that Gaia will observe in the Galaxy.

  15. INTERPRETATION OF AT-LINE SPECTRA FROM AFS-2 BATCH #3 FERROUS SULFAMATE TREATMENT

    SciTech Connect

    Kyser, E.; O'Rourke, P.

    2013-12-10

    Spectra from the “at-line” spectrometer were obtained during the ferrous sulfamate (FS) valence adjustment step of AFS-2 Batch #3 on 9/18/2013. These spectra were analyzed by mathematical principal component regression (PCR) techniques to evaluate the effectiveness of this treatment. Despite the complications from Pu(IV), we conclude that all Pu(VI) was consumed during the FS treatment, and that by the end of the treatment, about 85% was as Pu(IV) and about 15% was as Pu(III). Due to the concerns about the “odd” shape of the Pu(IV) peak and the possibility of this behavior being observed in the future, a follow-up sample was sent to SRNL to investigate this further. Analysis of this sample confirmed the previous results and concluded that it “odd” shape was due to an intermediate acid concentration. Since the spectral evidence shows complete reduction of Pu(VI) we conclude that it is appropriate to proceed with processing of this the batch of feed solution for HB-Line including the complexation of the fluoride with aluminum nitrate.

  16. High temperature dielectric properties of Apical, Kapton, Peek, Teflon AF, and Upilex polymers

    NASA Technical Reports Server (NTRS)

    Hammoud, A. N.; Baumann, E. D.; Overton, E.; Myers, I. T.; Suthar, J. L.; Khachen, W.; Laghari, J. R.

    1992-01-01

    Reliable lightweight systems capable of providing electrical power at the magawatt level are a requirement for future manned space exploration missions. This can be achieved by the development of high temperature insulating materials which are not only capable of surviving the hostile space environment but can contribute to reducing the mass and weight of the heat rejection system. In this work, Apical, Upilex, Kapton, Teflon AF, and Peek polymers are characterized for AC and DC dielectric breakdown in air and in silicone oil at temperatures up to 250 C. The materials are also tested in terms of their dielectric constant and dissipation factor at high temperatures with an electrical stress of 60 Hz, 200 V/mil present. The effects of thermal aging on the properties of the films are determined after 15 hours of exposure to 200 and 250 C, each. The results obtained are discussed and conclusions are made concerning the suitability of these dielectrics for use in capacitors and cable insulations in high temperature environments.

  17. The Detection of a Light Echo from Type Ia SN 2007af in NGC 5584

    NASA Astrophysics Data System (ADS)

    Drozdov, Dina; Leising, M. D.; Milne, P.; Riess, A. G.

    2013-06-01

    We report the discovery of a light echo (LE) at t ~1000 days past maximum from the normal Type Ia supernova (SNe Ia) SN 2007af in the spiral galaxy NGC 5584. The presence of a LE is supported by photometric data and analysis of the images acquired during the Cepheid campaign using the Hubble Space Telescope (HST) Wide Field Camera 3 (Riess et al. 2011). The F350 and F555 images show a distinct ring-like structure with an additional central source. The images, taken months apart, show an evolution of the ring structure, which is consistent with a growing light echo in time. We find an angular radius of the outer echo to be ~0.29'' - 0.36''. Using the Cepheid distance to NGC 5584 of 24 Mpc, we find the dust illuminated by the light echo to be at a distance ~800 pc from the supernova. This rare discovery adds to the select few light echoes found in Type Ia SNe: SN 1572, SN 1991T, SN 1995E, SN 1998bu, and SN 2006X. Light echoes are powerful tools that probe the environment around supernovae, determine dust properties and characteristics, and could provide constraints on the progenitors, which are not fully understood for SN Ia.

  18. Parathyroid cancer

    MedlinePlus

    ... the thyroid gland, which is located at the base of the neck. Parathyroid cancer is a very rare type of cancer. Men and women are equally affected. It usually occurs in people older than 30. The cause of parathyroid cancer ...

  19. Lung Cancer

    MedlinePlus

    Lung cancer is one of the most common cancers in the world. It is a leading cause of ... in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  20. Prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000380.htm Prostate cancer To use the sharing features on this page, please enable JavaScript. Prostate cancer is cancer that starts in the prostate gland. ...

  1. Cancer - penis

    MedlinePlus

    ... an organ that makes up part of the male reproductive system. Causes The exact cause is unknown. Smegma, a ... Squamous cell cancer - penis Images Male reproductive anatomy Male reproductive system References National Comprehensive Cancer Network. National Comprehensive Cancer ...

  2. Cancer Chemotherapy

    MedlinePlus

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  3. Stomach cancer

    MedlinePlus

    Cancer - stomach; Gastric cancer; Gastric carcinoma; Adenocarcinoma of the stomach ... Several types of cancer can occur in the stomach. The most common type is called adenocarcinoma. It starts from one of the cell ...

  4. Uterine Cancer

    MedlinePlus

    ... is pregnant. There are different types of uterine cancer. The most common type starts in the endometrium, the lining of the uterus. This type of cancer is sometimes called endometrial cancer. The symptoms of ...

  5. Cancer Moonshot

    Cancer.gov

    The Cancer Moonshot, led by Vice President Joe Biden, will marshal resources across the federal government to speed progress in cancer research and lead to improved cancer prevention, detection, and treatment.

  6. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  7. Thyroid Cancer

    MedlinePlus

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  8. Stomach Cancer

    MedlinePlus

    ... with stomach acid and helps digest protein. Stomach cancer mostly affects older people - two-thirds of people ... Smoke cigarettes Have a family history of stomach cancer It is hard to diagnose stomach cancer in ...

  9. Cancer Today

    MedlinePlus

    ... Society: Cancer Facts and Figures 2007 : NCI Cancer Screening Tests Screening tests can find diseases and conditions early when ... active or are older than 21. Prostate Cancer Screening (Men): Get advice from your doctor if you ...

  10. Ovarian Cancer

    MedlinePlus

    ... deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian ...

  11. Lung Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Lung Cancer What is Lung Cancer? How Tumors Form The body is made ... button on your keyboard.) Two Major Types of Lung Cancer There are two major types of lung ...

  12. Metastatic Cancer

    MedlinePlus

    ... cancers, including cancers of the blood and the lymphatic system ( leukemia , multiple myeloma , and lymphoma ), can form metastatic tumors. Although rare, the metastasis of blood and lymphatic system cancers to the lung, heart, central nervous system , ...

  13. Anal Cancer

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Anal Cancer Download Printable Version [PDF] » Whether you (or ... the topics below to get started. What Is Anal Cancer? What is anal cancer? What are the ...

  14. Thyroid cancer

    MedlinePlus

    ... cancer is a cancer that starts in the thyroid gland. The thyroid gland is located inside the front of your lower ... thyroid cells that are normally present in the thyroid gland. This form of thyroid cancer tends to occur ...

  15. Esophageal cancer

    MedlinePlus

    Cancer - esophagus ... Esophageal cancer is not common in the United States. It occurs most often in men over 50 years old. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. These two types ...

  16. Cancer Today

    MedlinePlus

    ... your doctor if you are considering having a prostate-specific antigen (PSA) test or digital rectal examination (DRE). Skin ... regular colonoscopy for cancer of the colon, serum prostatic-specific antigen (PSA) for prostate cancer, mammography for breast cancer, ...

  17. Skin Cancer

    MedlinePlus

    ... States. The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, ... If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ...

  18. Pancreatic Cancer

    MedlinePlus

    ... sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for ... therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. NIH: National Cancer Institute

  19. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another part of the body is more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 ...

  20. Human PSENEN and U2AF1L4 genes are concertedly regulated by a genuine bidirectional promoter.

    PubMed

    Didych, D A; Shamsutdinov, M F; Smirnov, N A; Akopov, S B; Monastyrskaya, G S; Uspenskaya, N Y; Nikolaev, L G; Sverdlov, E D

    2013-02-15

    Head-to-head genes with a short distance between their transcription start sites may constitute up to 10% of all genes in the genomes of various species. It was hypothesized that this intergenic space may represent bidirectional promoters which are able to initiate transcription of both genes, but the true bidirectionality was proved only for a few of them. We present experimental evidence that, according to several criteria, a 269 bp region located between the PSENEN and U2AF1L4 human genes is a genuine bidirectional promoter regulating a concerted divergent transcription of these genes. Concerted transcription of PSENEN and U2AF1L4 can be necessary for regulation of T-cell activity. PMID:23246698

  1. AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription.

    PubMed

    Okuda, Hiroshi; Kanai, Akinori; Ito, Shinji; Matsui, Hirotaka; Yokoyama, Akihiko

    2015-01-01

    Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL-AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL-AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation. PMID:26593443

  2. Birth order in transgendered males from Polynesia: a quantitative study of Samoan fa'afāfine.

    PubMed

    Poasa, Kris H; Blanchard, Ray; Zucker, Kenneth J

    2004-01-01

    In previous research, a late birth order has been shown to be a characteristic of Western homosexual transsexual men. To date, however, it is not clear if a late birth order is specific to Western transsexuals or may be a characteristic of non-Western transgendered males as well. We quantified birth order in a sample of 13 transgendered males known as fa'afāfine from Samoa. On average, the fa'afāfine were late born, both with regard to number of older brothers and number of older sisters, although the effect appeared to be somewhat stronger with regard to number of older brothers. We consider possible interpretations of the late birth order effect, along with recommendations for further research to identify common mechanisms that might underlie transgenderism across different cultural groups. PMID:14660290

  3. Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer.

    PubMed

    Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

    2015-11-01

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer. PMID:26431378

  4. Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer

    PubMed Central

    Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

    2015-01-01

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer. PMID:26431378

  5. Distinct binding determinants for 9-cis retinoic acid are located within AF-2 of retinoic acid receptor alpha.

    PubMed Central

    Tate, B F; Allenby, G; Janocha, R; Kazmer, S; Speck, J; Sturzenbecker, L J; Abarzúa, P; Levin, A A; Grippo, J F

    1994-01-01

    Retinoids exert their physiological action by interacting with two families of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which regulate gene expression by forming transcriptionally active heterodimeric RAR/RXR or homodimeric RXR/RXR complexes on DNA. Retinoid receptor activity resides in several regions, including the DNA and ligand binding domains, a dimerization interface, and both a ligand-independent (AF-1) and a ligand-dependent (AF-2) transactivation function. While 9-cis retinoic acid (RA) alone is the cognate ligand for the RXRs, both 9-cis RA and all-trans RA (t-RA) compete for binding with high affinity to the RARs. This latter observation suggested to us that the two isomers may interact with a common binding site. Here we report that RAR alpha has two distinct but overlapping binding sites for 9-cis RA and t-RA. Truncation of a human RAR alpha to 419 amino acids yields a receptor that binds both t-RA and 9-cis RA with high affinity, but truncation to amino acid 404 yields a mutant receptor that binds only t-RA with high affinity. Remarkably, this region also defines a C-terminal boundary for AF-2, as addition of amino acids 405 to 419 restores receptor-mediated gene activity to a truncated human RAR alpha lacking this region. It is interesting to speculate that binding of retinoid stereoisomers to unique sites within an RAR may function with AF-2 to cause differential activation of retinoid-responsive gene pathways. Images PMID:8139538

  6. AF-353, a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist

    PubMed Central

    Gever, Joel R; Soto, Rothschild; Henningsen, Robert A; Martin, Renee S; Hackos, David H; Panicker, Sandip; Rubas, Werner; Oglesby, Ian B; Dillon, Michael P; Milla, Marcos E; Burnstock, Geoffrey; Ford, Anthony PDW

    2010-01-01

    Background and purpose: Purinoceptors containing the P2X3 subunit (P2X3 homotrimeric and P2X2/3 heterotrimeric) are members of the P2X family of ion channels gated by ATP and may participate in primary afferent sensitization in a variety of pain-related diseases. The current work describes the in vitro pharmacological characteristics of AF-353, a novel, orally bioavailable, highly potent and selective P2X3/P2X2/3 receptor antagonist. Experimental approach: The antagonistic potencies (pIC50) of AF-353 for rat and human P2X3 and human P2X2/3 receptors were determined using methods of radioligand binding, intracellular calcium flux and whole cell voltage-clamp electrophysiology. Key results: The pIC50 estimates for these receptors ranged from 7.3 to 8.5, while concentrations 300-fold higher had little or no effect on other P2X channels or on an assortment of receptors, enzymes and transporter proteins. In contrast to A-317491 and TNP-ATP, competition binding and intracellular calcium flux experiments suggested that AF-353 inhibits activation by ATP in a non-competitive fashion. Favourable pharmacokinetic parameters were observed in rat, with good oral bioavailability (%F = 32.9), reasonable half-life (t1/2 = 1.63 h) and plasma-free fraction (98.2% protein bound). Conclusions and implications: The combination of a favourable pharmacokinetic profile with the antagonist potency and selectivity for P2X3 and P2X2/3 receptors suggests that AF-353 is an excellent in vivo tool compound for study of these channels in animal models and demonstrates the feasibility of identifying and optimizing molecules into potential clinical candidates, and, ultimately, into a novel class of therapeutics for the treatment of pain-related disorders. PMID:20590629

  7. Increased Mortality Associated with Digoxin in Contemporary Patients with Atrial Fibrillation: Findings from the TREAT-AF Study

    PubMed Central

    Turakhia, Mintu P.; Santangeli, Pasquale; Winkelmayer, Wolfgang C.; Xu, Xiangyan; Ullal, Aditya J.; Than, Claire T.; Schmitt, Susan; Holmes, Tyson H.; Frayne, Susan M.; Phibbs, Ciaran S.; Yang, Felix; Hoang, Donald D.; Ho, P. Michael; Heidenreich, Paul A.

    2014-01-01

    Objectives To evaluate the association of digoxin with mortality in atrial fibrillation. Background Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation and flutter (AF). Methods Using complete data from the US Department of Veterans Administration (VA) Health Care System, we identified patients with newly-diagnosed, non-valvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004-2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use to death. Residual confounding was assessed by sensitivity analysis. Results Of 122,465 patients with 353,168 person-years of follow-up (age 72.1±10.3 years, 98.4% males), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; P<0.001). Digoxin use was independently associated with mortality after multivariate adjustment (HR: 1.26, 95%CI: 1.23-1.29, P<0.001) and propensity matching (HR: 1.21, 95%CI: 1.17-1.25, P<0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta blockers, amiodarone, or warfarin. Conclusion Digoxin was associated with increased risk of death in patients with newly-diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF. PMID:25125296

  8. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  9. The M2 selective antagonist AF-DX 116 shows high affinity for muscarine receptors in bovine tracheal membranes.

    PubMed

    Roffel, A F; in't Hout, W G; de Zeeuw, R A; Zaagsma, J

    1987-05-01

    We have characterized the muscarine receptors in bovine tracheal and left ventricular membranes using 3H-dexetimide/pirenzepine and 3H-dexetimide/AF-DX 116 competition studies. Pirenzepine exhibited low (M2) affinity binding to both preparations; Kd was 590 nM in left ventricle and 463 nM in trachea. AF-DX 116 exhibited high (M2) affinity binding to left ventricle (Kd = 95.6 nM); in tracheal membranes it bound with high (M2) affinity (Kd = 40.7 nM) to 74% of the receptors and with low (M3) affinity (Kd = 2.26 microM) to 26% of the receptors. It is concluded that bovine tracheal muscle membranes contain a heterogeneous population of muscarine binding sites, the majority having M2 (heart) subtype characteristics and being located on the smooth muscle membranes; a minority having M3 (exocrine gland) subtype characteristics and presumed to be located in submucosal glands. This is the first report of high affinity binding of AF-DX 116 to non-cardiac peripheral muscarine receptors. PMID:3614390

  10. Differential role of Id1 in MLL-AF9-driven leukemia based on cell of origin.

    PubMed

    Man, Na; Sun, Xiao-Jian; Tan, Yurong; García-Cao, Marta; Liu, Fan; Cheng, Guoyan; Hatlen, Megan; Xu, Haiming; Shah, Ronit; Chastain, Nolan; Liu, Na; Huang, Gang; Zhou, Yuan; Sheng, Mengyao; Song, Junhong; Yang, Feng-Chun; Benezra, Robert; Nimer, Stephen D; Wang, Lan

    2016-05-12

    Inhibitor of DNA binding 1 (Id1) functions as an E protein inhibitor, and overexpression of Id1 is seen in acute myeloid leukemia (AML) patients. To define the effects of Id1 on leukemogenesis, we expressed MLL-AF9 in fetal liver (FL) cells or bone marrow (BM) cells isolated from wild-type, Id1(-/-), p21(-/-), or Id1(-/-)p21(-/-) mice, and transplanted them into syngeneic recipient mice. We found that although mice receiving MLL-AF9-transduced FL or BM cells develop AML, loss of Id1 significantly prolonged the median survival of mice receiving FL cells but accelerated leukemogenesis in recipients of BM cells. Deletion of Cdkn1a (p21), an Id1 target gene, can rescue the effect of Id1 loss in both models, suggesting that Cdkn1a is a critical target of Id1 in leukemogenesis. It has been suggested that the FL transplant model mimics human fetal-origin (infant) MLL fusion protein (FP)-driven leukemia, whereas the BM transplantation model resembles postnatal MLL leukemia; in fact, the analysis of clinical samples from patients with MLL-FP(+) leukemia showed that Id1 expression is elevated in the former and reduced in the latter type of MLL-FP(+) AML. Our findings suggest that Id1 could be a potential therapeutic target for infant MLL-AF9-driven leukemia. PMID:26944543

  11. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

    PubMed

    Fitzmaurice, David A; Accetta, Gabriele; Haas, Sylvia; Kayani, Gloria; Lucas Luciardi, Hector; Misselwitz, Frank; Pieper, Karen; Ten Cate, Hugo; Turpie, Alexander G G; Kakkar, Ajay K

    2016-08-01

    Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably. PMID:27071942

  12. Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development.

    PubMed

    Barrett, Neil A; Malouf, Camille; Kapeni, Chrysa; Bacon, Wendi A; Giotopoulos, George; Jacobsen, Sten Eirik W; Huntly, Brian J; Ottersbach, Katrin

    2016-07-26

    MLL-AF4+ infant B cell acute lymphoblastic leukemia is characterized by an early onset and dismal survival. It initiates before birth, and very little is known about the early stages of the disease's development. Using a conditional Mll-AF4-expressing mouse model in which fusion expression is targeted to the earliest definitive hematopoietic cells generated in the mouse embryo, we demonstrate that Mll-AF4 imparts enhanced B lymphoid potential and increases repopulation and self-renewal capacity during a putative pre-leukemic state. This occurs between embryonic days 12 and 14 and manifests itself most strongly in the lymphoid-primed multipotent progenitor population, thus pointing to a window of opportunity and a potential cell of origin. However, this state alone is insufficient to generate disease, with the mice succumbing to B cell lymphomas only after a long latency. Future analysis of the molecular details of this pre-leukemic state will shed light on additional events required for progression to acute leukemia. PMID:27396339

  13. The SRB recovery ship Liberty Star reenters the Hangar AF area at CCAS with a spent SRB used on STS-

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Seen carrying a spent solid rocket booster (SRB) from the STS-87 launch on Nov. 19 is the solid rocket booster recovery ship Liberty Star as it reenters the Hangar AF area at Cape Canaveral Air Station. Hangar AF is a building originally used for Project Mercury, the first U.S. manned space program. The SRBs are the largest solid propellant motors ever flown and the first designed for reuse. After a Shuttle is launched, the SRBs are jettisoned at two minutes, seven seconds into the flight. At six minutes and 44 seconds after liftoff, the spent SRBs, weighing about 165,000 lb., have slowed their descent speed to about 62 mph and splashdown takes place in a predetermined area. They are retrieved from the Atlantic Ocean by special recovery vessels and returned for refurbishment and eventual reuse on future Shuttle flights. Once at Hangar AF, the SRBs are unloaded onto a hoisting slip and mobile gantry cranes lift them onto tracked dollies where they are safed and undergo their first washing.

  14. Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia

    PubMed Central

    Owens, Kristina; Hatem, Layla; Glass, Carolyn H.; Karuppaiah, Kannan; Camargo, Fernando

    2013-01-01

    A subgroup of leukemogenic mixed-lineage leukemia (MLL) fusion proteins (MFPs) including MLL-AF9 activates the Mecom locus and exhibits extremely poor clinical prognosis. Mecom encodes EVI1 and MDS1-EVI1 (ME) proteins via alternative transcription start sites; these differ by the presence of a PRDI-BF1-RIZ1 (PR) domain with histone methyltransferase activity in the ME isoform. Using an ME-deficient mouse, we show that ME is required for MLL-AF9–induced transformation both in vitro and in vivo. And, although Nup98-HOXA9, MEIS1-HOXA9, and E2A-Hlf could transform ME-deficient cells, both MLL-AF9 and MLL-ENL were ineffective, indicating that the ME requirement is specific to MLL fusion leukemia. Further, we show that the PR domain is essential for MFP-induced transformation. These studies clearly indicate an essential role of PR-domain protein ME in MFP leukemia, suggesting that ME may be a novel target for therapeutic intervention for this group of leukemias. PMID:24021671

  15. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... for early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  16. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  17. Pattern Analysis of Acute Mucosal Reactions in Patients With Head and Neck Cancer Treated With Conventional and Accelerated Irradiation

    SciTech Connect

    Wygoda, Andrzej Maciejewski, Boguslaw; Skladowski, Krzysztof; Hutnik, Marcin; Pilecki, Boleslaw; Golen, Maria; Rutkowski, Tomasz

    2009-02-01

    Purpose: To evaluate severity of acute mucosal reactions (AMR) caused by conventional (CF) and accelerated fractionation (AF) regimens using a modified Dische system and to analyze differences in incidence and severity of AMR according to frequency and regularity of scoring. Methods and Materials: Sixty-six consecutive patients (33 CF, 33 AF) with head and neck cancer irradiated with 5 fractions in 5 days per week (CF) or with 7 fractions in 7 days (AF) to a total dose of 70 Gy. A modified Dische system was used for daily quantitation of AMR during radiotherapy until complete healing. Results: Confluent mucositis (CM) was noted in 79% of patients in the CF group and 85% in the AF group. In 24% of the CF group and 18% of the AF group the CM presented a wave-like pattern. In 55% of CF and 67% of AF a classic triphasic pattern was noted. In 12 patients acute reactions did not transgress the level of spotted mucositis. The present study clearly shows that quantitation of the incidence and severity of acute mucosal effects strongly depends on frequent and regular scoring. A significant difference in the incidence of CM between the CF and AF groups was noted, mainly in weeks 4-6 of irradiation. When once-weekly irregular instead of daily scoring was evaluated, the incidence of CM was underestimated by approximately 20-36%. Conclusions: Acute mucosal reactions occur as a complex of morphologic and functional disorders with individual intensity, even among patients treated with the same fractionation regimen. In some cases they present a 'wave-like' pattern during irradiation. Therefore, precise quantitation of acute effects requires regular and frequent scoring.

  18. Integrated Molecular Profiling in Advanced Cancers Trial

    ClinicalTrials.gov

    2016-08-19

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  19. Cancer Research Repository for Individuals With Cancer Diagnosis and High Risk Individuals.

    ClinicalTrials.gov

    2014-12-12

    Pancreatic Cancer; Thyroid Cancer; Lung Cancer; Esophageal Cancer; Thymus Cancer; Colon Cancer; Rectal Cancer; GIST; Anal Cancer; Bile Duct Cancer; Duodenal Cancer; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Small Intestine Cancer; Peritoneal Surface Malignancies; Familial Adenomatous Polyposis; Lynch Syndrome; Bladder Cancer; Kidney Cancer; Penile Cancer; Prostate Cancer; Testicular Cancer; Ureter Cancer; Urethral Cancer; Hypopharyngeal Cancer; Laryngeal Cancer; Lip Cancer; Oral Cavity Cancer; Nasopharyngeal Cancer; Oropharyngeal Cancer; Paranasal Sinus Cancer; Nasal Cavity Cancer; Salivary Gland Cancer; Skin Cancer; CNS Tumor; CNS Cancer; Mesothelioma

  20. Cancer of the Uterus (Endometrial Cancer)

    MedlinePlus

    ... Management Education & Events Advocacy For Patients About ACOG Cancer of the Uterus [Endometrial Cancer] Home For Patients Search FAQs Cancer of the ... Uterus [Endometrial Cancer] FAQ097, May 2011 PDF Format Cancer of the Uterus [Endometrial Cancer] Gynecologic Problems What ...

  1. Activated KRAS Cooperates with MLL-AF4 to Promote Extramedullary Engraftment and Migration of Cord Blood CD34+ HSPC But Is Insufficient to Initiate Leukemia.

    PubMed

    Prieto, Cristina; Stam, Ronald W; Agraz-Doblas, Antonio; Ballerini, Paola; Camos, Mireia; Castaño, Julio; Marschalek, Rolf; Bursen, Aldeheid; Varela, Ignacio; Bueno, Clara; Menendez, Pablo

    2016-04-15

    The MLL-AF4 (MA4) fusion gene is the genetic hallmark of an aggressive infant pro-B-acute lymphoblastic leukemia (B-ALL). Our understanding of MA4-mediated transformation is very limited. Whole-genome sequencing studies revealed a silent mutational landscape, which contradicts the aggressive clinical outcome of this hematologic malignancy. Only RAS mutations were recurrently detected in patients and found to be associated with poorer outcome. The absence of MA4-driven B-ALL models further questions whether MA4 acts as a single oncogenic driver or requires cooperating mutations to manifest a malignant phenotype. We explored whether KRAS activation cooperates with MA4 to initiate leukemia in cord blood-derived CD34(+) hematopoietic stem/progenitor cells (HSPC). Clonogenic and differentiation/proliferation assays demonstrated that KRAS activation does not cooperate with MA4 to immortalize CD34(+) HSPCs. Intrabone marrow transplantation into immunodeficient mice further showed that MA4 and KRAS(G12V) alone or in combination enhanced hematopoietic repopulation without impairing myeloid-lymphoid differentiation, and that mutated KRAS did not cooperate with MA4 to initiate leukemia. However, KRAS activation enhanced extramedullary hematopoiesis of MA4-expressing cell lines and CD34(+) HSPCs that was associated with leukocytosis and central nervous system infiltration, both hallmarks of infant t(4;11)(+) B-ALL. Transcriptional profiling of MA4-expressing patients supported a cell migration gene signature underlying the mutant KRAS-mediated phenotype. Collectively, our findings demonstrate that KRAS affects the homeostasis of MA4-expressing HSPCs, suggesting that KRAS activation in MA4(+) B-ALL is important for tumor maintenance rather than initiation. Cancer Res; 76(8); 2478-89. ©2016 AACR. PMID:26837759

  2. Predictors for Stroke and Death in Non-Anticoagulated Asian Patients with Atrial Fibrillation: The Fushimi AF Registry

    PubMed Central

    Hamatani, Yasuhiro; Yamashita, Yugo; Esato, Masahiro; Chun, Yeong-Hwa; Tsuji, Hikari; Wada, Hiromichi; Hasegawa, Koji; Abe, Mitsuru

    2015-01-01

    Background Atrial fibrillation (AF) increases the risk of stroke and death. Data on the predictors for stroke and death in ‘real-world’ AF patients are limited, especially from large prospective Asian cohorts. Methods The Fushimi AF Registry is a community-based prospective survey designed to enroll all AF patients who visited the participating medical institutions in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,304 patients (median follow-up period 741 days). We explored the predictors for ‘death, stroke, and systemic embolism (SE)’ during follow-up in 1,541 patients not receiving oral anticoagulants (OAC) at baseline. Results The mean age was 73.1 ± 12.5 years, and 673 (44%) patients were female. The mean CHADS2 and CHA2DS2-VASc scores were 1.76 and 3.08, respectively. Cumulative events were as follows: stroke/SE in 61 (4%) and death in 230 (15%), respectively. On multivariate analysis, advanced age (hazard ratio (HR): 1.68, 95% confidence interval (CI): 1.24–2.29), underweight (body mass index <18.5 kg/m2) (HR: 1.71, 95% CI: 1.25–2.32), previous stroke/SE/transient ischemic attack (HR: 1.70, 95% CI: 1.25–2.30), heart failure (HR: 1.59, 95% CI: 1.17–2.15), chronic kidney disease (HR: 1.53, 95% CI: 1.16–2.02), and anemia (HR: 2.41, 95% CI: 1.78–3.28) were independent predictors for death/stroke/SE. Cumulative numbers of these 6 risk predictors could stratify the incidence of death/stroke/SE in patients without OAC, as well as those with OAC in our registry. Conclusions Advanced age, underweight, previous stroke/SE/transient ischemic attack, heart failure, chronic kidney disease, and anemia were independently associated with the risk of death/stroke/SE in non-anticoagulated Japanese AF patients. PMID:26540107

  3. SERMs have substance-specific effects on bone, and these effects are mediated via ERαAF-1 in female mice.

    PubMed

    Börjesson, Anna E; Farman, Helen H; Movérare-Skrtic, Sofia; Engdahl, Cecilia; Antal, Maria Cristina; Koskela, Antti; Tuukkanen, Juha; Carlsten, Hans; Krust, Andrée; Chambon, Pierre; Sjögren, Klara; Lagerquist, Marie K; Windahl, Sara H; Ohlsson, Claes

    2016-06-01

    The bone-sparing effect of estrogens is mediated primarily via estrogen receptor (ER)α, which stimulates gene transcription through activation function (AF)-1 and AF-2. The role of ERαAF-1 for the estradiol (E2) effects is tissue specific. The selective ER modulators (SERMs) raloxifene (Ral), lasofoxifene (Las), and bazedoxifene (Bza) can be used to treat postmenopausal osteoporosis. They all reduce the risk for vertebral fractures, whereas Las and partly Bza, but not Ral, reduce the risk for nonvertebral fractures. Here, we have compared the tissue specificity of Ral, Las, and Bza and evaluated the role of ERαAF-1 for the effects of these SERMs, with an emphasis on bone parameters. We treated ovariectomized (OVX) wild-type (WT) mice and OVX mice lacking ERαAF-1 (ERαAF-1(0)) with E2, Ral, Las, or Bza. All three SERMs increased trabecular bone mass in the axial skeleton. In the appendicular skeleton, only Las increased the trabecular bone volume/tissue volume and trabecular number, whereas both Ral and Las increased the cortical bone thickness and strength. However, Ral also increased cortical porosity. The three SERMs had only a minor effect on uterine weight. Notably, all evaluated effects of these SERMs were absent in ovx ERαAF-1(0) mice. In conclusion, all SERMs had similar effects on axial bone mass. However, the SERMs had slightly different effects on the appendicular skeleton since only Las increased the trabecular bone mass and only Ral increased the cortical porosity. Importantly, all SERM effects require a functional ERαAF-1 in female mice. These results could lead to development of more specific treatments for osteoporosis. PMID:27048997

  4. A clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AF): design and rationale.

    PubMed

    Rao, Meena P; Ciobanu, Andrea O; Lopes, Renato D; Fox, Kathleen A; Xian, Ying; Pokorney, Sean D; Al-Khalidi, Hussein R; Jiang, Jei; Kamath, Deepak Y; Berwanger, Otavio; Xavier, Denis; Bahit, Cecilia M; Tajer, Carlos; Vinereanu, Dragos; Huo, Yong; Granger, Christopher B

    2016-06-01

    Atrial fibrillation (AF) is common, increasing as the population ages, and a major cause of embolic stroke. While oral anticoagulation (OAC) is highly effective at preventing stroke in patients with AF, it continues to be underused in eligible patients worldwide. The objective of this prospective, cluster randomized controlled trial (IMPACT-AF; ClinicalTrials.gov #NCT02082548) is to determine whether a comprehensive customized intervention will increase the rate and persistence of use of OAC in patients with AF. IMPACT-AF will be conducted in approximately 50 centers in 5 low- to middle-income countries. Before randomization, sites within countries will be paired to match in size, practice type and baseline rate of OAC use. Site pairs will be randomized to intervention versus control. In total, 40 to 70 patients with AF and at least 2 CHA2DS2-VASc risk factors will be enrolled at each site using a consecutive enrollment strategy, with the goal of capturing actual practice patterns. We aim for patients with a new diagnosis of AF to comprise at least 30% of the study cohort. Assuming an average baseline OAC use of 60% and a post-intervention use of 70% with a post-control rate of 60%, there will be roughly 94-98% power with 25 clusters per group (intracluster correlation coefficient of 0.02). While this trial focuses on improving treatment use and reducing preventable strokes, we also aim to better understand the reasons for OAC underuse. This will improve the intervention with the goal of creating educational recommendations to improve care for patients with AF. PMID:27264227

  5. Stroke prevention in atrial fibrillation and ‘real world’ adherence to guidelines in the Balkan Region: The BALKAN-AF Survey

    PubMed Central

    Potpara, Tatjana S.; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S.; Polovina, Marija M.; Petranov, Stanislav L.; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y. H.; Potpara, Tatjana S.; Polovina, Marija; Milanov, Srdjan; Pavlovic, Marija; Petrovic, Marijana; Simovic, Stefan; Mitic, Gorana; Milanov, Marko; Savic, Jelena; Gnip, Sanja; Radovic, Pavica; Markovic, Snezana; Koncarevic, Ivana; Gavrilovic, Jelena; Acimovic, Tijana; Djikic, Dijana; Malic, Semir; Hodzic, Jusuf; Stojanovic, Milovan; Ilic, Marina Deljanin; Zlatar, Milan; Matic, Dragan; Lazic, Snezana; Peric, Vladan; Markovic, Sanja; Kovacevic, Snezana; Arandjelovic, Aleksandra; Asanin, Milika; Zdravkovic, Marija; Dan, Gheorghe-Andrei; Breha, Anca; Dan, Anca Rodica; Musetescu, Rodica; Popescu, Mircea Ioachim; Badila, Elisabeta; Georgescu, Catalina Arsenescu; Pop, Sorina; Popescu, Raluca; Neamtu, Simina; Oancea, Floriana; Trendafilova, Elina; Dimitrova, Elena; Goshev, Evgenii; Velichkova, Anna; Petranov, Stanislav; Kamenova, Delyana; Kamenova, Penka; Elefterova, Svetoslava; Shterev, Valentin; Zekova, Maria; Diukiandzhieva, Stela; Dimitrov, Boiko; Sotirov, Tihomir; Simeonova, Valentina; Drianovska, Dimitrina; Boiadzhieva, Liliya Ivanova Vasileva; Buchukova, Darina; Goda, Artan; Paparisto, Vilma; Gjergo, Hortensia; Mijo, Alma; Shirka, Ervina; Gjini, Viktor; Ekmekciu, Uliks; Refatllari, Ina; Kusljugic, Zumreta; Loncar, Daniela; Mrsic, Denis; Tulumovic, Hazim; Pojskic, Belma; Sijamija, Alma; Bijedic, Amira; Karamujic, Indira; Bijedic, Irma; Halilovic, Sanela; Sokolovic, Sekib; Manola, Sime; Zeljkovic, Ivan; Pavlovic, Nikola; Radeljic, Vjekoslav; Brusich, Sandro; Anic, Ante; Jeric, Melita; Pekic, Petar; Milas, Kresimir; Music, Ljilja; Bulatovic, Nebojsa; Nenezic, Ana; Asanovic, Dijana

    2016-01-01

    Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary ‘real-world’ AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the ‘truly low-risk’ patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID:26869284

  6. Hazard identification and risk characterization of bisphenols A, F and AF to aquatic organisms.

    PubMed

    Tišler, Tatjana; Krel, Alja; Gerželj, Urška; Erjavec, Boštjan; Dolenc, Marija Sollner; Pintar, Albin

    2016-05-01

    Production of bisphenol A (BPA) analogues such as bisphenol F (BPF) and bisphenol AF (BPAF) has recently increased, due to clear evidence of adverse effects of BPA on humans and wildlife. Bisphenols (BPs) have already been released into aquatic environment without previous available information about potential adverse effects of BPs and their potential risk to aquatic ecosystems. In this study, lethal and sublethal effects of BPF and BPAF to bacteria, algae, crustacea and fish embryos were investigated and the results were compared to the adverse effects obtained for BPA. We found that BPAF was the most toxic compound to Daphnia magna, Danio rerio and Desmodesmus subspicatus; the lowest 72 h EC50 (median effective concentration) and 21 d NOEC (no observed effect concentration) values were determined at 2.2 mg/L regarding zebrafish hatching success and 0.23 mg/L of BPAF obtained for growth and reproduction of water fleas, respectively. In most cases, BPA was more toxic to D. magna, D. rerio and D. subspicatus in comparison to BPF, but pigmentation of zebrafish embryos after 48 h of exposure and reproduction of water fleas after 21-day D. magna reproductive test exposure to BPF were much more impaired. Risk quotients (measured environmental concentration/21 d NOEC) showed that BPA, BPF and BPAF are recently not chronically hazardous to the survival, reproduction and growth of water fleas in surface waters. On the other hand, we importantly show that currently present BPAF concentrations in surface waters could cause a potential ecological risk to aquatic organisms. In the near future, higher concentrations of BPF and BPAF in surface waters are anticipated and for this reason further testing using test systems with various aquatic species and endpoints are needed to provide additional information about toxic impacts of BPF and BPAF on aquatic biota. PMID:26957022

  7. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

    PubMed Central

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-01-01

    Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

  8. Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF.

    PubMed

    Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

    2015-10-01

    Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3',5-triiodothyronine (TT3), total 3,5,3',5'-tetraiodothyronine (TT4), free 3,3',5-triiodothyronine (FT3) and free 3,5,3',5'-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

  9. The action of neuropeptide AF on passive avoidance learning. Involvement of neurotransmitters.

    PubMed

    Palotai, Miklós; Telegdy, Gyula; Bagosi, Zsolt; Jászberényi, Miklós

    2016-01-01

    Neuropeptide AF (NPAF) is an amidated octadecapeptide, which is member of the RFamide peptide family. NPAF is encoded by the farp-1 gene and acts through the G protein coupled NPFF-1 and NPFF-2 receptors. NPAF is involved in several physiological functions of the central nervous system, however we have little evidence about the involvement of NPAF in learning and memory. Therefore, the aim of the present study was to investigate the action of NPAF on consolidation of memory in a passive avoidance learning paradigm in mice. We have also investigated the underlying neurotransmissions and the action of NPAF on β-amyloid-induced memory impairment. Accordingly, mice were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a non-selective opioid receptor antagonist, naloxone, a nitric oxide synthase inhibitor, nitro-l-arginine, a α1/α2β-adrenergic receptor antagonist, prazosin, a nonselective β-adrenergic receptor antagonist, propranolol or β-amyloid 25-35 in combination with NPAF administration. Our results demonstrate for the first time that NPAF improves the consolidation of passive avoidance learning. This effect is mediated through muscarinic cholinergic, 5HT1- and 5HT2-serotoninergic, dopaminergic, nitrergic and α- and β-adrenergic neurotransmissions, but not by opioid transmission, since atropine, cyproheptadine, methysergide, haloperidol, nitro-l-arginine, prazosin and propranolol reversed the action of NPAF, whereas naloxone was ineffective. The present study also shows that NPAF reverses the β-amyloid 25-35-induced memory impairment. PMID:26639667

  10. Neuropeptide AF induces anxiety-like and antidepressant-like behavior in mice.

    PubMed

    Palotai, Miklós; Telegdy, Gyula; Tanaka, Masaru; Bagosi, Zsolt; Jászberényi, Miklós

    2014-11-01

    Little is known about the action of neuropeptide AF (NPAF) on anxiety and depression. Only our previous study provides evidence that NPAF induces anxiety-like behavior in rats. Therefore, the aim of the present study was to investigate the action of NPAF on depression-like behavior and the underlying neurotransmissions in mice. In order to determine whether there are species differences between rats and mice, we have investigated the action of NPAF on anxiety-like behavior in mice as well. A modified forced swimming test (mFST) and an elevated plus maze test (EPMT) were used to investigate the depression and anxiety-related behaviors, respectively. Mice were treated with NPAF 30min prior to the tests. In the mFST, the animals were pretreated with a non-selective muscarinic acetylcholine receptor antagonist, atropine, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2/D3/D4 dopamine receptor antagonist, haloperidol, a α1/α2β-adrenergic receptor antagonist, prazosin or a non-selective β-adrenergic receptor antagonist, propranolol 30min before the NPAF administration. In the mFST, NPAF decreased the immobility time and increased the climbing and swimming times. This action was reversed completely by methysergide and partially by atropine, whereas cyproheptadine, haloperidol, prazosin and propranolol were ineffective. In the EPMT, NPAF decreased the time spent in the arms (open/open+closed). Our results demonstrate that NPAF induces anti-depressant-like behavior in mice, which is mediated, at least in part, through 5HT2-serotonergic and muscarinic cholinergic neurotransmissions. In addition, the NPAF-induced anxiety is species-independent, since it develops also in mice. PMID:25116251

  11. Letter to the Editor: H-1, C-13 and N-15 Assignments for the Archaeglobus fulgidis Protein AF2095.

    SciTech Connect

    Powers, Robert; Acton, Thomas; Chiang, Yiwen; Rajan, Paranji K.; Cort, John R.; Kennedy, Michael A.; Liu, Jinfeng; Ma, LiChung; Rost, Burkhard; Montelione, Gaetano

    2004-09-01

    The Human genome project promises to provide an unprecedented wealth of information on cell biology, development, evolution and physiology. Translating this immense increase in genomic information into advances in medicine and human health requires a concerted effort to explore and investigate the structure and molecular activity for the vast amount of proteins in the Human proteome that lack any such explicit experimental information. Structural genomics is providing a means to determine the molecular and cellular function of these proteins by characterizing the complete range of protein folds (Montelione, 2001). By annotating sequence information with a protein structure, it is sometimes possible to decipher the biochemical activity of hypothetical proteins from structural similarity and the conservation of spatial arrangement of active site residues. Homology can often be inferred by structural similarity even in the absence of recognizable sequence similarity, and can sometimes be used to identify functional relationships between distantly related proteins. Determining an experimental structure for each protein in a proteome is currently impractical because of the significant time commitment and resources required by X-ray and NMR. Therefore, the current paradigm of structural genomics is to determine a representative structure for each cluster of homologous protein domain sequences that lack similarity to a protein domain with a known structure. In this manner, comparative modeling using a single experimental structure can provide approximate but useful 3D structural information for an entire protein domain family. The Northeast Structural Genomics Consortium (NESG; www.nesg.org) is a pilot project funded by the National Institutes of Health Protein Structure Initiative, focusing on proteins from eukaryotic model organisms including humans. The thermophillic archaea Archaeglobus fulgidis AF2095 protein is an example of a protein of unknown biological function

  12. [Effect of down-regulating mll-af9 gene expression on proliferation of acute monocytic leukemia cell line THP-1].

    PubMed

    Li, Lei; Zhang, Ai-Hua; Liu, Ling-Bo; Bi, Lan; Wang, Li; Zhao, Ya-Jie; Zou, Ping

    2008-04-01

    This study was aimed to investigate the effect of small interfering RNA (siRNA) on the expression of mll-af9 oncogene and the proliferation of human acute monocytic leukemia cell line THP-1. One group of siRNA was designed targeting mll-af9 mRNA and finally obtained by chemosynthesis. Then the obtained siRNA was transfected into cultured human acute monocytic leukemia cell line THP-1 by lipofectamine. Flow cytometry was used to detect siRNA transfection efficiency. The level of mll-af9 mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). The cell proliferation rate was assayed by MTT. The change of cell cycles and apoptosis rate was detected by flow cytometry. The results showed that the siRNA transfection efficiency was 69.1%+/-1.8%. The level of mll-af9 mRNA expression was significantly inhibited in siRNA-transfected cells as compared with the controls. mll-af9-targeted siRNA inhibited the proliferation of THP-1 cells and induced cell apoptosis effectively after transfection. The percentage of G0/G1 phase cells significantly increased in siRNA-transfected cells in comparion with the control cells, but the percentage of S phase cells significantly decreased. It is concluded that the mll-af9-targeted siRNA can effectively inhibit the proliferation of human acute monocytic leukemia cell line THP-1. PMID:18426643

  13. Complexity Generation in Fungal Peptidyl Alkaloid Biosynthesis: Oxidation of Fumiquinazoline A to the Heptacyclic Hemiaminal Fumiquinazoline C by the Flavoenzyme Af12070 from Aspergillus fumigatus†

    PubMed Central

    Ames, Brian D.; Haynes, Stuart W.; Gao, Xue; Evans, Bradley S; Kelleher, Neil L.; Tang, Yi; Walsh, Christopher T.

    2011-01-01

    The human pathogen Aspergillus fumigatus makes a series of fumiquinazoline (FQ) peptidyl alkaloids of increasing scaffold complexity using L-Trp, two equivalents of L-Ala, and the non-proteinogenic amino acid anthranilate as building blocks. The FQ gene cluster encodes two nonribosomal peptide synthetases (NRPS) and two flavoproteins. The trimodular NRPS Af12080 assembles FQF (the first level of complexity) while the next two enzymes, Af12060 and Af12050, act in tandem in an oxidative annulation sequence to couple alanine to the indole side chain of FQF to yield the imidazolindolone-containing FQA. In this study we show that the fourth enzyme, the mono-covalent flavoprotein Af12070, introduces a third layer of scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by catalyzing the formation of a transient imine within the pyrazinone ring (and therefore acting in an unprecedented manner as an FAD-dependent amide oxidase). FQC subsequently converts non-enzymatically to the known cyclic aminal FQD. We also investigated the effect of substrate structure on Af12070 activity and subsequent cyclization with a variety of FQA analogues, including an FQA diastereomer (2′-epi-FQA) which is an intermediate in the fungal biosynthesis of the tremorgenic tryptoquialanine. 2′-epi-FQA is processed by Af12070 to epi-FQD, not epi-FQC, illustrating that the delicate balance in product cyclization regiochemistry can be perturbed by a remote stereochemical center. PMID:21899262

  14. Influence of cytochrome c on apoptosis induced by Anagrapha (Syngrapha) falcifera multiple nuclear polyhedrosis virus (AfMNPV) in insect Spodoptera litura cells.

    PubMed

    Liu, Lijun; Peng, Jianxin; Liu, Kaiyu; Yang, Hong; Li, Yi; Hong, Huazhu

    2007-09-01

    We investigated the influence of cytochrome c on apoptosis induced by Anagrapha (Syngrapha) falcifera multiple nuclear polyhedrosis virus (AfMNPV). Microscopic observation revealed that infection of SL-1 cells with AfMNPV resulted in apoptosis, displaying apoptotic bodies in fluorescent-stained nuclei of AfMNPV-infected SL-1cells. Western blot analysis demonstrated that AfMNPV-induced apoptosis in insect SL-1 cells was significantly inhibited by cyclosporin A which blocked a translocation of cytochrome c from the mitochondria to the cytosol. As determined by using AC-DEVD-AFC as substrate, the activity of caspase-3 in AfMNPV-induced cells was detected as early as 4h post infection, gradually increased with time extension, and reached a highest level after 16h of infection. However, activity of caspase-3 in apoptotic cells decreased in the presence of cyclosporin A (30microM), indicating that activation of caspase-3 in SfaMNPV-induced cells was dependent on the release of cytochrome c from the mitochondria. In addition, cyclosporin A could markedly inhibit mitochondrial transmembrane potential (DeltaPsim) disruption in undergoing apoptotic cells. These data indicate that cytochrome c plays a key role in AfMNPV-induced apoptosis in S. litura cells and may be required for caspase activation during the induction of apoptosis. PMID:17478109

  15. Lung Cancer

    MedlinePlus

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  16. Vaginal Cancer

    MedlinePlus

    Vaginal cancer is a rare type of cancer. It is more common in women 60 and older. You are also more likely to get it if you have had a human ... test can find abnormal cells that may be cancer. Vaginal cancer can often be cured in its ...

  17. What Is Breast Cancer?

    MedlinePlus

    ... Next Topic Types of breast cancers What is breast cancer? Breast cancer starts when cells in the breast ... breast cancer? ” and Non-cancerous Breast Conditions . How Breast Cancer Spreads Breast cancer can spread through the lymph ...

  18. Diet and cancer

    MedlinePlus

    Fiber and cancer; Cancer and fiber; Nitrates and cancer; Cancer and nitrates ... DIET AND BREAST CANCER The link between nutrition and breast cancer has been well studied. To reduce risk of breast cancer the American ...

  19. Prostate cancer - resources

    MedlinePlus

    Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  20. Radon and Cancer

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  1. Cervical Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  2. NCI Designated Cancer Centers

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Cancer Center History Frederick National Laboratory for Cancer Research Partners ... Profiles in Cancer Research Outstanding Investigator Award Recipients ...

  3. Endometrial Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  4. Prostate Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  5. Metastatic cancer to the lung

    MedlinePlus

    ... Bladder cancer Breast cancer Colon cancer Kidney cancer Neuroblastoma Prostate cancer Sarcoma Wilms tumor Symptoms Symptoms may ... Breast cancer Cancer Chemotherapy Colon cancer Lung cancer Neuroblastoma Prostate cancer Radiation therapy Wilms tumor Update Date ...

  6. Exposure to Bisphenol AF disrupts sex hormone levels and vitellogenin expression in zebrafish.

    PubMed

    Yang, Xiaoxi; Liu, Yuchen; Li, Jia; Chen, Minjie; Peng, Di; Liang, Yong; Song, Maoyong; Zhang, Jie; Jiang, Guibin

    2016-03-01

    Bisphenol AF (BPAF) is widely used in food-contact products, electronic devices, and as a cross-linking reagent in fluoroelastomers. There are growing concerns about its toxicity and endocrine-disrupting effects based on its structural similarity with bisphenol A (BPA). The endocrine-disrupting effects of BPAF were studied by exposing 2-month-old zebrafish to 0, 0.05, 0.25, or 1 mg/L BPAF for 28 days and evaluating the effect on growth, histopathology, hormone levels, enzyme activity, and gene expression. The overall fitness was not significantly affected. There were no apparent alterations in the gills and intestine tissues of both sexes after BPAF exposure. However, exposure to 1 mg/L BPAF caused damage to the liver in the male fish, characterized by hepatocellular swelling and vacuolation. There was no obvious effect in the liver of female fish, suggesting that the hepatic toxicity of BPAF is gender dependent. Gonadal examination indicated that exposure to 1 mg/L BPAF caused induction of acellular areas in the testis and retardation of oocyte development in the ovary. BPAF exposure increased free triiodothyronine levels of females in a dose-dependent manner. In males, the testosterone levels decreased in a concentration-dependent manner. In contrast, estradiol levels increased in a concentration-dependent manner and were significantly higher in males exposed to 1 mg/L BPAF compared with the controls. In females, 0.05 and 0.25 mg/L BPAF caused an increase in testosterone levels. Furthermore, the estradiol levels increased in females exposed to 0.05 and 1 mg/L. We observed an upregulation of hepatic vitellogenin in both sexes and significantly higher levels in males exposed to 1 mg/L BPAF and females exposed to 0.25 mg/L BPAF, suggesting that BPAF has an estrogenic activity. Our results indicate that BPAF is an endocrine-disrupting chemical that exerts reproductive toxicity and estrogenic effects on zebrafish. PMID:25213402

  7. Effect of targeted ovarian cancer therapy using amniotic fluid mesenchymal stem cells transfected with enhanced green fluorescent protein-human interleukin-2 in vivo.

    PubMed

    You, Qi; Yao, Yuan; Zhang, Yuanlong; Fu, Songbin; Du, Mei; Zhang, Guangmei

    2015-10-01

    The aim of the present study was to investigate the effect of using amniotic fluid mesenchymal stem cells (AF-MSCs) in targeted ovarian cancer therapy in vivo. AF-MSCs were isolated from human second trimester AF and a plasmid, enhanced green fluorescent protein‑human interleukin‑2 (pEGFP‑hIL‑2) was formed. The plasmid was stably transfected into the AF‑MSCs and the cells were intravenously injected into ovarian cancer nude mice models. Following stable transfection of the vector, tumor formation, and the expression and activity of hIL‑2 were investigated, and microscopic pathological examinations of the tumor were performed. It was found that AF‑MSCs exhibited high motility during migration in vivo, and the vector, pEGFP‑hIL‑2 can be stably transfected into AF‑MSCs. Following stable transfection, this type of stem cell is able to successfully transport the therapeutic gene, IL-2, migrate to the ovarian cancer tumor site to secrete the functional IL-2 and treat the tumor. Thus, AF-MSCs may serve as transporters for therapeutic genes targeting ovarian tumor sites and, therefore, be involved in the treatment of tumors. PMID:26179662

  8. Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.

    PubMed

    Spencer, Ryan J; Amerena, John V

    2015-12-01

    Atrial fibrillation (AF) is an increasingly common cause of stroke and systemic embolism. While warfarin has been the mainstay of stroke prevention in patients with AF, newer novel oral anticoagulant medications are now available. Rivaroxaban, a direct factor Xa inhibitor with a rapid onset and offset after oral administration, offers potential advantages over warfarin, predominantly due to its predictable pharmacokinetics across wide patient populations. It requires no coagulation monitoring, and only two different doses are needed (20 mg daily for patients with normal renal function and 15 mg daily in those with reduced renal function). A large randomized trial (ROCKET AF) has shown non-inferiority to warfarin for preventing stroke or systemic embolism in the per-protocol population and superiority to warfarin in the on-treatment safety population. Several subanalyses confirm that the treatment effect of rivaroxaban is consistent across different patient subgroups, including those with reduced renal function. The tolerability of rivaroxaban appears similar to that of warfarin, with comparable overall bleeding rates in clinical trials. In ROCKET AF, significantly lower rates of fatal and intracranial bleeding were seen with rivaroxaban, while lower rates of gastrointestinal bleeding were seen with warfarin. Important contraindications to rivaroxaban include valvular AF, the presence of a prosthetic valve (mechanical or bioprosthetic) or valve repair, the need for concurrent dual antiplatelet therapy, and creatinine clearance <30 ml/min. Once-daily dosing and the lack of coagulation monitoring may increase utilization and adherence compared with warfarin, potentially decreasing the large burden of care associated with stroke secondary to AF. Overall, rivaroxaban offers a useful alternative to warfarin for stroke prevention in patients with AF. PMID:26062914

  9. Photometric properties for selected algol-type binaries. VIII. The triple systems DI Peg and AF Gem revisited

    SciTech Connect

    Yang, Yuan-Gui; Li, Shu-Zheng; Yang, Ying E-mail: yangyg@chnu.edu.cn

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are f{sub p} = 78.2(± 0.4)% for DI Peg, and f{sub p} = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O–C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P {sub 3} = 54.6(± 0.5) yr and P {sub 4} = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M {sub in} = 0.095 M {sub ☉} and M {sub out} = 0.170 M {sub ☉}, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  10. Catalytic soman scavenging by Y337A/F338A acetylcholinesterase mutant assisted with novel site-directed aldoximes

    PubMed Central

    Kovarik, Zrinka; Hrvat, Nikolina Maček; Katalinić, Maja; Sit, Rakesh K.; Paradyse, Alexander; Žunec, Suzana; Musilek, Kamil; Fokin, Valery V.; Taylor, Palmer; Radić, Zoran

    2016-01-01

    Exposure to the nerve agent soman is difficult to treat due to the rapid dealkylation of soman-acetylcholinesterase (AChE) conjugate known as aging. Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. To overcome this limitation, we tested ex vivo, in human blood, and in vivo, in soman exposed mice, the capacity of aging-resistant human AChE mutant Y337A/F338A in combination with oxime HI-6 to act as a catalytic bioscavenger of soman. HI-6 was previously shown in vitro to efficiently reactivate this mutant upon soman, as well as VX, cyclosarin, sarin and paraoxon inhibition. We here demonstrate that ex vivo, in whole human blood, 1 μM soman was detoxified within 30 minutes when supplemented with 0.5 μM Y337A/F338A AChE and 100 μM HI-6. This combination was further tested in vivo. Catalytic scavenging of soman in mice improved the therapeutic outcome and resulted in the delayed onset of toxicity symptoms. Furthermore, in a preliminary in vitro screen we identified an even more efficacious oxime than HI-6, in a series of forty-two pyridinium aldoximes, and five imidazole 2-aldoxime N-propyl pyridinium derivatives. One of the later imidazole aldoximes, RS-170B, was a 2–3 –fold more effective reactivator of Y337A/F338A AChE than HI-6 due to the smaller imidazole ring, as indicated by computational molecular models, that affords a more productive angle of nucleophilic attack. PMID:25835984

  11. Photometric Properties for Selected Algol-type Binaries. VIII. The Triple Systems DI Peg and AF Gem Revisited

    NASA Astrophysics Data System (ADS)

    Yang, Yuan-Gui; Yang, Ying; Li, Shu-Zheng

    2014-06-01

    New extensive photometry for two triple binary stars, DI Peg and AF Gem, was performed from 2012 October to 2013 January, with two small telescopes at Xinglong station (XLs) of NAOC. From new multi-color observations and previously published ones in literature, the photometric models were (re)deduced using the updated Wilson-Devinney code. The results indicated that the low third lights exist in two classic Algol-type binaries, whose fill-out factors for the more massive components are fp = 78.2(± 0.4)% for DI Peg, and fp = 69.0(± 0.3)% for AF Gem, respectively. Through analyzing the O-C curves, the orbital periods for two binaries change in the complicated mode. The period of DI Peg possibly appears to show two light-time orbits, whose modulated periods are P 3 = 54.6(± 0.5) yr and P 4 = 23.0(± 0.6) yr, respectively. The inferred minimum masses for the inner and outer sub-stellar companions are M in = 0.095 M ⊙ and M out = 0.170 M ⊙, respectively. Therefore, DI Peg may be a quadruple star. The orbital period of AF Gem appears to show a continuous period decrease or a cyclic variation; the latter may be preferable. The cyclic oscillation, with a period of 120.3(± 2.5) yr, may be attributed to the light-time effect due to the third body. This kind of additional companion may extract angular momentum from the central system, which may play a key role in the evolution of the binary.

  12. The ultraviolet-bright, slowly declining transient PS1-11af as a partial tidal disruption event

    SciTech Connect

    Chornock, R.; Berger, E.; Zauderer, B. A.; Kamble, A.; Soderberg, A. M.; Czekala, I.; Dittmann, J.; Drout, M.; Foley, R. J.; Fong, W.; Kirshner, R. P.; Lunnan, R.; Marion, G. H.; Narayan, G.; Gezari, S.; Rest, A.; Riess, A. G.; Chomiuk, L.; Huber, M. E.; Lawrence, A.; and others

    2014-01-01

    We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only ∼0.002 M {sub ☉}, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.

  13. Single-Unit Activity during Natural Vision: Diversity, Consistency, and Spatial Sensitivity among AF Face Patch Neurons

    PubMed Central

    Russ, Brian E.; Elnaiem, Heba D.; Kurnikova, Anastasia I.; Leopold, David A.

    2015-01-01

    Several visual areas within the STS of the macaque brain respond strongly to faces and other biological stimuli. Determining the principles that govern neural responses in this region has proven challenging, due in part to the inherently complex stimulus domain of dynamic biological stimuli that are not captured by an easily parameterized stimulus set. Here we investigated neural responses in one fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques freely view complex videos rich with natural social content. Longitudinal single-unit recordings allowed for the accumulation of each neuron's responses to repeated video presentations across sessions. We found that individual neurons, while diverse in their response patterns, were consistently and deterministically driven by the video content. We used principal component analysis to compute a family of eigenneurons, which summarized 24% of the shared population activity in the first two components. We found that the most prominent component of AF activity reflected an interaction between visible body region and scene layout. Close-up shots of faces elicited the strongest neural responses, whereas far away shots of faces or close-up shots of hindquarters elicited weak or inhibitory responses. Sensitivity to the apparent proximity of faces was also observed in gamma band local field potential. This category-selective sensitivity to spatial scale, together with the known exchange of anatomical projections of this area with regions involved in visuospatial analysis, suggests that the AF face patch may be specialized in aspects of face perception that pertain to the layout of a social scene. PMID:25855170

  14. Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

    PubMed

    Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

    2014-04-01

    Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum. PMID:24605815

  15. NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis

    PubMed Central

    Stewart, Fiona; Eisinga, Anne

    2016-01-01

    Background Warfarin has been the anticoagulant of choice for the prevention of ischaemic stroke in patients with atrial fibrillation (AF). Novel oral anticoagulants (NOACs) are increasingly used as an alternative. Objectives The objective of this review was to evaluate the efficacy and safety of the NOACs versus warfarin in patients with AF. Search methods Medline, EMBASE and grey literature search for all phase II and III randomised control trials. Data collection/analysis Two authors independently reviewed abstracts and performed data extraction of eligible full-text articles. Revman V.5 was used for meta-analysis. Main results 12 studies were identified with a total study population of 77 011. NOACs demonstrated a reduction in the composite of stroke or systemic embolic events OR 0.85 (95% CI 0.75 to 0.98), a 52% reduction in intracranial haemorrhage OR 0.48 (95% CI 0.40 to 0.57) and a 14% reduction in mortality OR 0.86 (0.82 to 0.91). The 30-day end of study switch to warfarin demonstrated an in increase in stroke or systemic embolic events OR 2.60 (95% CI 1.61 to 4.18) and an increase in major bleeding OR 2.19 (95% CI 1.42 to 3.36). Conclusions NOACs are superior to warfarin for the prevention of the composite of stroke and systemic embolism in patients with AF and an additional risk factor for stroke. There is a significant reduction in intracranial haemorrhage, which drives the finding of significantly lower mortality. During the poststudy switch from NOACs to warfarin there is an excess of the composite of stroke and systemic embolism as well as major bleeding events, which may be of significance in clinical practice. PMID:26848392

  16. AFS-2 FLOWSHEET MODIFICATIONS TO ADDRESS THE INGROWTH OF PU(VI) DURING METAL DISSOLUTION

    SciTech Connect

    Crapse, K.; Rudisill, T.; O'Rourke, P.; Kyser, E.

    2014-07-02

    In support of the Alternate Feed Stock Two (AFS-2) PuO{sub 2} production campaign, Savannah River National Laboratory (SRNL) conducted a series of experiments concluding that dissolving Pu metal at 95°C using a 6–10 M HNO{sub 3} solution containing 0.05–0.2 M KF and 0–2 g/L B could reduce the oxidation of Pu(IV) to Pu(VI) as compared to dissolving Pu metal under the same conditions but at or near the boiling temperature. This flowsheet was demonstrated by conducting Pu metal dissolutions at 95°C to ensure that PuO{sub 2} solids were not formed during the dissolution. These dissolution parameters can be used for dissolving both Aqueous Polishing (AP) and MOX Process (MP) specification materials. Preceding the studies reported herein, two batches of Pu metal were dissolved in the H-Canyon 6.1D dissolver to prepare feed solution for the AFS-2 PuO{sub 2} production campaign. While in storage, UV-visible spectra obtained from an at-line spectrophotometer indicated the presence of Pu(VI). Analysis of the solutions also showed the presence of Fe, Ni, and Cr. Oxidation of Pu(IV) produced during metal dissolution to Pu(VI) is a concern for anion exchange purification. Anion exchange requires Pu in the +4 oxidation state for formation of the anionic plutonium(IV) hexanitrato complex which absorbs onto the resin. The presence of Pu(VI) in the anion feed solution would require a valence adjustment step to prevent losses. In addition, the presence of Cr(VI) would result in absorption of chromate ion onto the resin and could limit the purification of Pu from Cr which may challenge the purity specification of the final PuO{sub 2} product. Initial experiments were performed to quantify the rate of oxidation of Pu(IV) to Pu(VI) (presumed to be facilitated by Cr(VI)) as functions of the HNO{sub 3} concentration and temperature in simulated dissolution solutions containing Cr, Fe, and Ni. In these simulated Pu dissolutions studies, lowering the temperature from near boiling

  17. Terraced copper growth deposited onto Teflon AF1600 by the excimer laser irradiation of Cu(hfac)TMVS

    SciTech Connect

    Popovici, D.; Piyakis, K.; Sacher, E.; Meunier, M.

    1996-12-31

    The authors are studying the feasibility of constructing Cu/fluoropolymer multilayer devices, in an effort to reduce both metal R and insulator C, a necessary condition in VLSI and GSI microelectronic applications. The laser chemical vapor deposition (LCVD) of the organometallic precursor Cu(hfac)TMVS (hexafluoroacetylacetonate)(trimethylvinylsilane) is used to grow copper films on a Teflon AF1600 substrate. Exposure to excimer laser radiation at 248 nm results in a terraced copper growth. A simple model, based on interference effects in the Teflon and copper layers, is presented to account for this structure.

  18. Eye Cancer

    MedlinePlus

    Cancer of the eye is uncommon. It can affect the outer parts of the eye, such as the eyelid, which are made up ... adults are melanoma and lymphoma. The most common eye cancer in children is retinoblastoma, which starts in ...

  19. Liver Cancer

    MedlinePlus

    ... body digest food, store energy, and remove poisons. Primary liver cancer starts in the liver. Metastatic liver ... and spreads to your liver. Risk factors for primary liver cancer include Having hepatitis B or C ...

  20. Nasal Cancer

    MedlinePlus

    ... the way to your throat as you breathe. Cancer of the nasal cavity and paranasal sinuses is ... be like those of infections. Doctors diagnose nasal cancer with imaging tests, lighted tube-like instruments that ...

  1. Pancreatic Cancer

    MedlinePlus

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  2. Esophageal Cancer

    MedlinePlus

    ... from your throat to your stomach. Early esophageal cancer usually does not cause symptoms. Later, you may ... You're at greater risk for getting esophageal cancer if you smoke, drink heavily, or have acid ...

  3. Gallbladder Cancer

    MedlinePlus

    ... your gallbladder and liver to your small intestine. Cancer of the gallbladder is rare. It is more ... the abdomen It is hard to diagnose gallbladder cancer in its early stages. Sometimes doctors find it ...

  4. Prostate Cancer

    MedlinePlus

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  5. Intestinal Cancer

    MedlinePlus

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  6. Colorectal Cancer

    MedlinePlus

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  7. Thymus Cancer

    MedlinePlus

    ... cell. These cells help protect you from infections. Cancer of the thymus is rare. You are more ... Sometimes there are no symptoms. Other times, thymus cancer can cause A cough that doesn't go ...

  8. Cancer Chemotherapy

    MedlinePlus

    ... cells grow and die in a controlled way. Cancer cells keep forming without control. Chemotherapy is drug ... Your course of therapy will depend on the cancer type, the chemotherapy drugs used, the treatment goal ...

  9. Bladder cancer

    MedlinePlus

    Transitional cell carcinoma of the bladder; Urothelial cancer ... In the United States, bladder cancer usually starts from the cells lining the bladder. These cells are called transitional cells. These tumors are classified by the way ...

  10. Colorectal Cancer

    MedlinePlus

    ... and rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... both men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  11. Cervical Cancer

    MedlinePlus

    ... the place where a baby grows during pregnancy. Cervical cancer is caused by a virus called HPV. The ... for a long time, or have HIV infection. Cervical cancer may not cause any symptoms at first. Later, ...

  12. Cervical cancer

    MedlinePlus

    ... and cervical cancer cannot be seen with the naked eye. Special tests and tools are needed to ... Pap smears and cervical cancer References Committee on Adolescent Health Care of the American College of Obstetricians ...

  13. Eye Cancer

    MedlinePlus

    ... adults are melanoma and lymphoma. The most common eye cancer in children is retinoblastoma, which starts in the cells of the retina. ... from other parts of the body. Treatment for eye cancer varies by the type and by how advanced ...

  14. Prostate Cancer

    MedlinePlus

    ... a man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... men younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  15. Skin Cancer

    MedlinePlus

    ... early. If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ... and a type of laser light to kill cancer cells. Biologic therapy boosts your body's own ability to ...

  16. Oral Cancer

    MedlinePlus

    ... use. Some oral cancers are linked to human papilloma virus (HPV) infections of the mouth and throat. ... The number of oropharyngeal cancers linked to human papilloma virus (HPV) has risen dramatically over the past ...

  17. Cancer treatments

    MedlinePlus

    ... cells. Targeted treatment zeroes in on specific targets (molecules) in cancer cells. These targets play a role ... Cryotherapy Also called cryosurgery , this therapy uses very cold gas to freeze and kill cancer cells. It ...

  18. Ovarian cancer

    MedlinePlus

    ... of ovarian cancer Already been diagnosed with ovarian cancer to determine how well treatment is working Other tests that may be done include: Complete blood count and blood chemistry Pregnancy test (serum HCG) CT or MRI of ...

  19. Occupational Cancer

    MedlinePlus

    ... Carcinogen List Cancer Clusters Cancer Policy at NIOSH Diesel Exhaust in Miners Study (DEMS) Related Topics Asbestos ... Toxicology Program Report on Carcinogens NIOSH Pocket Guide Diesel Exhaust in Miners Study (DEMS) Recent NIOSH Research ...

  20. Cervical Cancer

    MedlinePlus

    ... Centers for Disease Control and Prevention’s (CDC) Inside Knowledge: Get the Facts About Gynecologic Cancer campaign. The ... the facts about gynecologic cancer, providing important “inside knowledge” about their bodies and health. Get the Facts ...

  1. Uterine Cancer

    MedlinePlus

    ... Centers for Disease Control and Prevention’s (CDC) Inside Knowledge: Get the Facts About Gynecologic Cancer campaign. The ... the facts about gynecologic cancer, providing important “inside knowledge” about their bodies and health. Get the Facts ...

  2. Colon cancer

    MedlinePlus

    ... red or processed meats Have colorectal polyps Have inflammatory bowel disease ( Crohn disease or ulcerative colitis ) Have a family history of colon cancer Have a personal history of breast cancer Some inherited diseases also increase the risk ...

  3. Thyroid Cancer

    MedlinePlus

    ... of treatments. They may include surgery, radioactive iodine, hormone treatment, radiation therapy, chemotherapy, or targeted therapy. Targeted therapy uses substances that attack cancer cells without harming normal cells. NIH: National Cancer Institute

  4. Atg5-dependent autophagy contributes to the development of acute myeloid leukemia in an MLL-AF9-driven mouse model.

    PubMed

    Liu, Qiang; Chen, Longgui; Atkinson, Jennifer M; Claxton, David F; Wang, Hong-Gang

    2016-01-01

    Acute myeloid leukemia (AML) is a hierarchical hematopoietic malignancy originating from leukemic stem cells (LSCs). Autophagy is a lysosomal degradation pathway that is hypothesized to be important for the maintenance of AML as well as contribute to chemotherapy response. Here we employ a mouse model of AML expressing the fusion oncogene MLL-AF9 and explore the effects of Atg5 deletion, a key autophagy protein, on the malignant transformation and progression of AML. Consistent with a transient decrease in colony-forming potential in vitro, the in vivo deletion of Atg5 in MLL-AF9-transduced bone marrow cells during primary transplantation prolonged the survival of recipient mice, suggesting that autophagy has a role in MLL-AF9-driven leukemia initiation. In contrast, deletion of Atg5 in malignant AML cells during secondary transplantation did not influence the survival or chemotherapeutic response of leukemic mice. Interestingly, autophagy was found to be involved in the survival of differentiated myeloid cells originating from MLL-AF9-driven LSCs. Taken together, our data suggest that Atg5-dependent autophagy may contribute to the development but not chemotherapy sensitivity of murine AML induced by MLL-AF9. PMID:27607576

  5. The transactivation domain AF-2 but not the DNA-binding domain of the estrogen receptor is required to inhibit differentiation of avian erythroid progenitors.

    PubMed

    von Lindern, M; Boer, L; Wessely, O; Parker, M; Beug, H

    1998-02-01

    Earlier work demonstrated that an activated estrogen receptor (ER) is required for long-term self-renewal of c-ErbB-expressing avian erythroid progenitors. Here, we demonstrate that activation of the ER does not only arrest or retard differentiation of early progenitors but that it affects erythroid differentiation at all stages of erythroid maturation. A search for genes whose expression is affected by the ER showed that the 17beta-estradiol-activated receptor suppressed the differentiation-associated up-regulation of Gata-1, SCL-1, and globin genes in partially mature cells. In the same cells, the expression of carbonic anhydrase II (CAII) and histone H5 was enhanced. This led to premature expression of CAII, a possible explanation for the toxic effects of overexpressed ER. Repression specifically required the transactivation domain AF-2, but neither an intact DNA-binding domain (DBD) nor the AF-1 domain. The transcriptional activation of CAII, however, required both an intact AF-2 and a functional DBD. The requirement for the AF-2, but not the DBD, suggested that the ER may compete with other nuclear hormone receptors for transcriptional coactivators that bind AF-2, a domain well conserved within this family of transcription factors. We show, however, that this model does not apply for the most likely candidate, the avian thyroid hormone receptor. PMID:9482667

  6. Prostate cancer

    SciTech Connect

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  7. Cancer Triptych.

    PubMed

    Faulkner, Sandra L

    2016-08-01

    The author uses personal narrative to show how the cold cloak of cancer covered her family during the polar vortex of 2013-2014. The use of a triptych form hinges together related themes of containment, coping, communicative responses, and social support after a cancer diagnosis. This narrative demonstrates the multiple responses and communicative coping strategies to a cancer diagnosis. PMID:26752448

  8. Testicular Cancer

    MedlinePlus

    ... of skin behind the penis. You can get cancer in one or both testicles. Testicular cancer mainly affects young men between the ages of ... undescended testicle Have a family history of the cancer Symptoms include pain, swelling, or lumps in your ...

  9. Breast Cancer

    MedlinePlus

    Breast cancer affects one in eight women during their lives. No one knows why some women get breast cancer, but there are many risk factors. Risks that ... who have family members with breast or ovarian cancer may wish to be tested for the genes. ...

  10. Cancer pain

    SciTech Connect

    Swerdlow, M.; Ventafridda, V.

    1987-01-01

    This book contains 13 chapters. Some of the chapter titles are: Importance of the Problem; Neurophysiology and Biochemistry of Pain; Assessment of Pain in Patients with Cancer; Drug Therapy; Chemotherapy and Radiotherapy for Cancer Pain; Sympton Control as it Relates to Pain Control; and Palliative Surgery in Cancer Pain Treatment.

  11. Breast cancer.

    PubMed

    Pearce, Lynne

    2016-08-17

    Essential facts Breast cancer is the most common cancer in the UK, with around 60,000 new cases diagnosed each year, according to the charity Breast Cancer Care. Over a lifetime, women have a one in eight risk of developing it. PMID:27533387

  12. Cancer Basics

    MedlinePlus

    ... of cells , tiny units that make up all living things. Cancer (also known as malignancy , pronounced: muh-LIG- ... cancer and cancer treatments can disrupt a person's life for a while. People ... to take care of the things they have to get done. For example, teens ...

  13. Cervical Cancer

    MedlinePlus

    ... dysplasia of the cervix, vagina, or vulva • A family history of cervical cancer •Smoking •Certain sexually transmitted infections , such as chlamydia • ... to treat your cancer, you still need cervical cancer screening. Cells are taken from the upper vagina ... smallest units of a structure in the body; the building blocks for all ...

  14. What is Prostate Cancer?

    MedlinePlus

    ... Topic Key statistics for prostate cancer What is prostate cancer? Cancer starts when cells in the body begin ... through the center of the prostate. Types of prostate cancer Almost all prostate cancers are adenocarcinomas . These cancers ...

  15. Breast Cancer Prevention

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Prevention (PDQ®)–Patient Version What is prevention? Go ... to keep cancer from starting. General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  16. Throat or larynx cancer

    MedlinePlus

    Vocal cord cancer; Throat cancer; Laryngeal cancer; Cancer of the glottis; Cancer of oropharynx or hypopharynx ... use tobacco are at risk of developing throat cancer. Drinking too much alcohol over a long time ...

  17. National Cancer Institute

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  18. Inflammatory Breast Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  19. Secondhand Smoke and Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  20. Psychological Stress and Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  1. Photodynamic Therapy for Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  2. Snapshot of Stomach Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  3. Electromagnetic Fields and Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  4. Antioxidants and Cancer Prevention

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  5. Biological Therapies for Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  6. Snapshot of Pediatric Cancers

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  7. Head and Neck Cancers

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  8. Helicobacter pylori and Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  9. Colon cancer - resources

    MedlinePlus

    Resources - colon cancer ... The following organizations are good resources for information on colon cancer : American Cancer Society -- www.cancer.org/cancer/colonandrectumcancer/index Colon Cancer Alliance -- www.ccalliance.org National ...

  10. Snapshot of Esophageal Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  11. Throat or larynx cancer

    MedlinePlus

    Vocal cord cancer; Throat cancer; Laryngeal cancer; Cancer of the glottis; Cancer of oropharynx or hypopharynx ... or use tobacco are at risk of developing throat cancer. Drinking too much alcohol over a long ...

  12. Understanding Cancer Prognosis

    MedlinePlus Videos and Cool Tools

    ... Screening & Early Detection Treatment Cancer & Public Health Cancer Health Disparities Childhood Cancers Research Clinical Trials Global Health Key ... Screening & Early Detection Treatment Cancer & Public Health Cancer Health Disparities Childhood Cancer Clinical Trials Global Health Key Initiatives ...

  13. [Simultaneous determination of arsanilic, nitarsone and roxarsone residues in foods of animal origin by ASE-LC-AFS].

    PubMed

    Xiao, Ya-Bing; Zhang, Man; Wen, Hua-Wei

    2014-04-01

    A method for simultaneous determination of arsanilic, nitarsone and roxarsone (ROX) residues in foods of animal origin was developed by accelerated solvent extraction-liquid chromatography-atomic fluorescence spectrometry (ASE-LC-AFS). The ultrasound centrifugation extraction and accelerated solvent extraction were compared, and the accelerated solvent extraction conditions, namely the proportion of the extraction solvent, the extraction temperature, extraction time and extraction times, were optimized. The operating conditions of LC-AFS and the mobile phase were optimized. Under the optimal conditions, the calibration curves for ASA , NIT and ROX were linear over the concentration range of 0-2.0 mg x L(-1) and their correlation coefficients were 0.999 2-0.999 8. The detection limits of ASA, NIT and ROX were 2.4, 7.4 and 4.1 microg x L(-1) respectively. The average recoveries of ASA, NIT and ROX from two samples spiked at three levels of 0.5, 2, 5 mg x kg(-1) were in the ranges of 87.1%-93.2%, 85.2%-93.9%, and 84.2%-93.7% with RSDs of 1.4%-4.6%, 1.2%-4.2%, and 1.1%-4.5%, respectively. This method possesses the merits of convenience and good repeatability, and is a feasible method for analysis of ASA, NIT and ROX in foods of animal origin. PMID:25007637

  14. Speciation of antimony in airborne particulate matter using ultrasound probe fast extraction and analysis by HPLC-HG-AFS.

    PubMed

    Bellido-Martín, A; Gómez-Ariza, J L; Smichowsky, P; Sánchez-Rodas, D

    2009-09-01

    A fast extraction procedure has been developed for Sb(III) and Sb(V) oxoanions speciation in airborne particulate matter samples. Different extraction media (diammonium tartrate, hidroxilammonium clorhidrate, citric acid+ascorbic acid, phosphoric acid and citrate solutions) were tried, with assistance of an ultrasonic probe. The operation power and time of extraction were also optimized. The higher extraction recoveries were obtained with a 100 mmol L(-1) hidroxilammonium clorhidrate aqueous solution assisted by the ultrasound probe operated at 50 W during 3 min. The extracts were analyzed by HPLC-HG-AFS. The chromatographic separation of Sb(III) and Sb(V) was also optimized using diammonium tartrate and phthalic acid as mobile phases. The separation of both Sb species was performed in less than 3 min under isocratic conditions, using a 200 mmol L(-1) diammonium tartrate solution. The proposed extraction procedure and the HPLC-HG-AFS instrumental coupling have been successfully applied to airborne particulate matter samples, with high Sb content, collected in heavy traffic streets from Buenos Aires (Argentina). The results showed the presence of both Sb species at similar concentrations in the ng m(-3) level. The extraction yield was higher than 90% for all the analyzed samples. PMID:19699393

  15. Linear quadratic game and non-cooperative predictive methods for potential application to modelling driver-AFS interactive steering control

    NASA Astrophysics Data System (ADS)

    Na, Xiaoxiang; Cole, David J.

    2013-02-01

    This paper is concerned with the modelling of strategic interactions between the human driver and the vehicle active front steering (AFS) controller in a path-following task where the two controllers hold different target paths. The work is aimed at extending the use of mathematical models in representing driver steering behaviour in complicated driving situations. Two game theoretic approaches, namely linear quadratic game and non-cooperative model predictive control (non-cooperative MPC), are used for developing the driver-AFS interactive steering control model. For each approach, the open-loop Nash steering control solution is derived; the influences of the path-following weights, preview and control horizons, driver time delay and arm neuromuscular system (NMS) dynamics are investigated, and the CPU time consumed is recorded. It is found that the two approaches give identical time histories as well as control gains, while the non-cooperative MPC method uses much less CPU time. Specifically, it is observed that the introduction of weight on the integral of vehicle lateral displacement error helps to eliminate the steady-state path-following error; the increase in preview horizon and NMS natural frequency and the decline in time delay and NMS damping ratio improve the path-following accuracy.

  16. Comparison of the ferromagnetic Blume-Emery-Griffiths model and the AF spin-1 longitudinal Ising model at low temperature

    NASA Astrophysics Data System (ADS)

    Thomaz, M. T.; Corrêa Silva, E. V.

    2016-03-01

    We derive the exact Helmholtz free energy (HFE) of the standard and staggered one-dimensional Blume-Emery-Griffiths (BEG) model in the presence of an external longitudinal magnetic field. We discuss in detail the thermodynamic behavior of the ferromagnetic version of the model, which exhibits magnetic field-dependent plateaux in the z-component of its magnetization at low temperatures. We also study the behavior of its specific heat and entropy, both per site, at finite temperature. The degeneracy of the ground state, at T=0, along the lines that separate distinct phases in the phase diagram of the ferromagnetic BEG model is calculated, extending the study of the phase diagram of the spin-1 antiferromagnetic (AF) Ising model in S.M. de Souza and M.T. Thomaz, J. Magn. and Magn. Mater. 354 (2014) 205 [5]. We explore the implications of the equality of phase diagrams, at T=0, of the ferromagnetic BEG model with K/|J| = - 2 and of the spin-1 AF Ising model for D/|J| > 1/2.

  17. L17A/F19A Substitutions Augment the α-Helicity of β-Amyloid Peptide Discordant Segment

    PubMed Central

    Wang, Chih-Ching; Chen, Yi-Ru; Chang, Chi-Fon; Shiao, Ming-Shi; Chen, Yi-Cheng; Lin, Ta-Hsien

    2016-01-01

    β-amyloid peptide (Aβ) aggregation has been thought to be associated with the pathogenesis of Alzheimer’s disease. Recently, we showed that L17A/F19A substitutions may increase the structural stability of wild-type and Arctic-type Aβ40 and decrease the rates of structural conversion and fibril formation. However, the underlying mechanism for the increase of structural stability as a result of the alanine substitutions remained elusive. In this study, we apply nuclear magnetic resonance and circular dichroism spectroscopies to characterize the Aβ40 structure, demonstrating that L17A/F19A substitutions can augment the α-helicity of the residues located in the α/β-discordant segment (resides 15 to 23) of both wild-type and Arctic-type Aβ40. These results provide a structural basis to link the α-helicity of the α/β-discordant segment with the conformational conversion propensity of Aβ. PMID:27104649

  18. [Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

    PubMed

    Ishikawa, Shinya; Kasai, Yoshitaka; Matsuura, Natsumi; Tarumi, Shintaro; Nakano, Jun; Okuda, Masaya; Goto, Masashi; Ryu, Dagu; Go, Tetsuhiko; Yokomise, Hiroyasu

    2015-04-01

    In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes. PMID:25836998

  19. Pancreatic Cancer

    PubMed Central

    Maitra, Anirban; Hruban, Ralph H.

    2009-01-01

    The past two decades have witnessed an explosion in our understanding of pancreatic cancer, and it is now clear that pancreatic cancer is a disease of inherited (germ-line) and somatic gene mutations. The genes mutated in pancreatic cancer include KRAS2, p16/CDKN2A, TP53, and SMAD4/DPC4, and these are accompanied by a substantial compendium of genomic and transcriptomic alterations that facilitate cell cycle deregulation, cell survival, invasion, and metastases. Pancreatic cancers do not arise de novo, and three distinct precursor lesions have been identified. Experimental models of pancreatic cancer have been developed in genetically engineered mice, which recapitulate the multistep progression of the cognate human disease. Although the putative cell of origin for pancreatic cancer remains elusive, minor populations of cells with stem-like properties have been identified that appear responsible for tumor initiation, metastases, and resistance of pancreatic cancer to conventional therapies. PMID:18039136

  20. Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.

    PubMed Central

    vom Baur, E; Zechel, C; Heery, D; Heine, M J; Garnier, J M; Vivat, V; Le Douarin, B; Gronemeyer, H; Chambon, P; Losson, R

    1996-01-01

    Using a yeast two-hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand- and AF-2 activating domain (AF-2 AD)-dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with mSUG1 and TIF1; (ii) the amphipathic alpha-helix core of the AF-2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (iii) the AF-2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus, the interaction interfaces between the different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF-2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF-2 of nuclear receptors through different mechanisms. Images PMID:8598193

  1. Role of 20-HETE in the impaired myogenic and TGF responses of the Af-Art of Dahl salt-sensitive rats.

    PubMed

    Ge, Ying; Murphy, Sydney R; Fan, Fan; Williams, Jan Michael; Falck, John R; Liu, Ruisheng; Roman, Richard J

    2014-09-01

    The present study examined whether 20-HETE production is reduced in the renal vasculature and whether this impairs myogenic or tubuloglomerular feedback (TGF) responses of the afferent arteriole (Af-Art). The production of 20-HETE was 73% lower in renal microvessels of Dahl salt-sensitive rats (SS) rats than in SS.5(BN) rats, in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes was transferred into the SS genetic background. The luminal diameter of the Af-Art decreased by 14.7 ± 1.5% in SS.5(BN) rats when the perfusion pressure was increased from 60 to 120 mmHg, but it remained unaltered in SS rats. Administration of an adenosine type 1 receptor agonist (CCPA, 1 μM) reduced the diameter of the Af-Art in the SS.5(BN) rats by 44 ± 2%, whereas the diameter of the Af-Art of SS rats was unaltered. Autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) was significantly impaired in SS rats but was intact in SS.5(BN) rats. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), completely blocked the myogenic and adenosine responses in the Af-Art and autoregulation of RBF and PGC in SS.5(BN) rats, but it had no effect in SS rats. These data indicate that a deficiency in the formation of 20-HETE in renal microvessels impairs the reactivity of the Af-Art of SS rats and likely contributes to the development of hypertension induced renal injury. PMID:25007877

  2. Differential Estrogenic Actions of Endocrine-Disrupting Chemicals Bisphenol A, Bisphenol AF, and Zearalenone through Estrogen Receptor α and β in Vitro

    PubMed Central

    Li, Yin; Burns, Katherine A.; Arao, Yukitomo; Luh, Colin J.

    2012-01-01

    Background: Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogen-like activity is attributed to EDCs, such as bisphenol A (BPA), bisphenol AF (BPAF), and zearalenone (Zea), but mechanisms of action and diversity of effects are poorly understood. Objectives: We used in vitro models to evaluate the mechanistic actions of BPA, BPAF, and Zea on estrogen receptor (ER) α and ERβ. Methods: We used three human cell lines (Ishikawa, HeLa, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ERα and ERβ. Ishikawa/ERα stable cells were used to determine changes in estrogen response element (ERE)-mediated target gene expression or rapid action-mediated effects. Results: The three EDCs showed strong estrogenic activity as agonists for ERα in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ERα in Ishikawa cells and BPAF acted as an antagonist for ERβ in HeLa cells, whereas Zea was only a partial antagonist for ERα. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ERα, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ERα target genes and rapid signaling via the p44/42 MAPK pathway were activated by BPA, BPAF, and Zea. Conclusion: BPA and BPAF can function as EDCs by acting as cell type–specific agonists (≥ 10 nM) or antagonists (≤ 10 nM) for ERα and ERβ. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ERα. In addition, all three compounds induced the rapid action-mediated response for ERα. PMID:22494775

  3. Heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex demonstrated by the selective antagonist AF-DX 116

    SciTech Connect

    Bloom, J.W.; Halonen, M.; Seaver, N.A.; Yamamura, H.I.

    1987-07-27

    Recent studies have demonstrated that the majority of muscarinic receptors in rabbit peripheral lung homogenates bind pirenzepine with high affinity (putative M1 subtype). In experiments of AF-DX 116 inhibiting (TH)(-)quinuclidinyl benzilate or (TH)pirenzepine, the authors found similar inhibitory constants for AF-DX 116 binding in rat heart and rabbit peripheral lung that were 4-fold smaller (i.e. of higher affinity) than the inhibitory constant for rat cerebral cortex. This results demonstrates heterogeneity of the M1 muscarinic receptor subtype between peripheral lung and cerebral cortex. 20 references, 1 figure, 2 tables.

  4. Clinical Validation of Targeted Next Generation Sequencing for Colon and Lung Cancers

    PubMed Central

    D’Haene, Nicky; Le Mercier, Marie; De Nève, Nancy; Blanchard, Oriane; Delaunoy, Mélanie; El Housni, Hakim; Dessars, Barbara; Heimann, Pierre; Remmelink, Myriam; Demetter, Pieter; Tejpar, Sabine; Salmon, Isabelle

    2015-01-01

    Objective Recently, Next Generation Sequencing (NGS) has begun to supplant other technologies for gene mutation testing that is now required for targeted therapies. However, transfer of NGS technology to clinical daily practice requires validation. Methods We validated the Ion Torrent AmpliSeq Colon and Lung cancer panel interrogating 1850 hotspots in 22 genes using the Ion Torrent Personal Genome Machine. First, we used commercial reference standards that carry mutations at defined allelic frequency (AF). Then, 51 colorectal adenocarcinomas (CRC) and 39 non small cell lung carcinomas (NSCLC) were retrospectively analyzed. Results Sensitivity and accuracy for detecting variants at an AF >4% was 100% for commercial reference standards. Among the 90 cases, 89 (98.9%) were successfully sequenced. Among the 86 samples for which NGS and the reference test were both informative, 83 showed concordant results between NGS and the reference test; i.e. KRAS and BRAF for CRC and EGFR for NSCLC, with the 3 discordant cases each characterized by an AF <10%. Conclusions Overall, the AmpliSeq colon/lung cancer panel was specific and sensitive for mutation analysis of gene panels and can be incorporated into clinical daily practice. PMID:26366557

  5. An imaging agent to detect androgen receptor and its active splice variants in prostate cancer

    PubMed Central

    Imamura, Yusuke; Tien, Amy H.; Pan, Jinhe; Leung, Jacky K.; Banuelos, Carmen A.; Jian, Kunzhong; Wang, Jun; Mawji, Nasrin R.; Fernandez, Javier Garcia; Lin, Kuo-Shyan; Andersen, Raymond J.; Sadar, Marianne D.

    2016-01-01

    Constitutively active splice variants of androgen receptor (AR-Vs) lacking ligand-binding domain (LBD) are a mechanism of resistance to androgen receptor LBD–targeted (AR LBD–targeted) therapies for metastatic castration-resistant prostate cancer (CRPC). There is a strong unmet clinical need to identify prostate cancer patients with AR-V–positive lesions to determine whether they will benefit from further AR LBD–targeting therapies or should receive taxanes or investigational drugs like EPI-506 or galeterone. Both EPI-506 (NCT02606123) and galeterone (NCT02438007) are in clinical trials and are proposed to have efficacy against lesions that are positive for AR-Vs. AR activation function-1 (AF-1) is common to the N-terminal domains of full-length AR and AR-Vs. Here, we provide proof of concept for developing imaging compounds that directly bind AR AF-1 to detect both AR-Vs and full-length AR. 123I-EPI-002 had specific binding to AR AF-1, which enabled direct visualization of CRPC xenografts that express full-length AR and AR-Vs. Our findings highlight the potential of 123I-EPI-002 as an imaging agent for the detection of full-length AR and AR-Vs in CRPC. PMID:27525313

  6. Lymphedema After Surgery in Patients With Endometrial Cancer, Cervical Cancer, or Vulvar Cancer

    ClinicalTrials.gov

    2014-12-23

    Lymphedema; Stage IA Cervical Cancer; Stage IA Uterine Corpus Cancer; Stage IA Vulvar Cancer; Stage IB Cervical Cancer; Stage IB Uterine Corpus Cancer; Stage IB Vulvar Cancer; Stage II Uterine Corpus Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIIA Vulvar Cancer; Stage IIIB Vulvar Cancer; Stage IIIC Vulvar Cancer; Stage IVB Vulvar Cancer

  7. Ceylonamides A-F, Nitrogenous Spongian Diterpenes That Inhibit RANKL-Induced Osteoclastogenesis, from the Marine Sponge Spongia ceylonensis.

    PubMed

    El-Desoky, Ahmed H; Kato, Hikaru; Angkouw, Esther D; Mangindaan, Remy E P; de Voogd, Nicole J; Tsukamoto, Sachiko

    2016-08-26

    Seven new spongian diterpenes, ceylonamides A-F (1-6) and 15α,16-dimethoxyspongi-13-en-19-oic acid (7), were isolated from the Indonesian marine sponge Spongia ceylonensis along with eight known spongian diterpenes, 8-15. Compounds 1-6 were determined to be nitrogenous spongian diterpenes. The isolated compounds were examined for the inhibition of RANKL-induced osteoclastogenesis in RAW264 macrophages. Ceylonamide A (1) exhibited the most potent inhibitory activity with an IC50 value of 13 μM, followed by ceylonamide B (2) (IC50, 18 μM). An examination of the structure-activity relationships of the isolated compounds revealed that the position of the carbonyl group of the γ-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity. PMID:27526327

  8. A comprehensive study of methyl and ethylmercury determination in natural water by adsorbent preconcentration an GC/AFS analysis

    SciTech Connect

    Cai, Y.; Jaffe, R.; Jones, R.

    1996-10-01

    This paper presents a sample preparation method for the determination of MeHg and ethylmercury (EtHg) in water samples by adsorbent preconcentration and capillary gas chromatography/atomic fluorescence detection (GC/AFS). MeHg and EtHg were preconcentrated from water on to a screening column packed with sulfhydryl cotton fiber (SCF) adsorbent. The MeHg and EtHg were elated by a mixture of acidic potassium bromide and copper sulfate solution, and then extracted using dichloromethane. Breakthrough volume of the SCF column used was tested using high organic matter-containing water from the Florida Everglades and seawater from Florida Bay. Good recoveries were achieved for both MeHg (85%) and EtHg (70%), and no breakthrough was found up to 2 L of sample. The detection limit was 0.01 ng/L in a 2 L water sample for both MeHg and EtHg.

  9. Structure of the MLL CXXC domain – DNA complex and its functional role in MLL-AF9 leukemia

    PubMed Central

    Cierpicki, Tomasz; Risner, Laurie E.; Grembecka, Jolanta; Lukasik, Stephen M.; Popovic, Relja; Omonkowska, Monika; Shultis, David S.; Zeleznik-Le, Nancy J.; Bushweller, John H.

    2010-01-01

    MLL (Mixed Lineage Leukemia) is the target of chromosomal translocations which cause leukemias with poor prognosis. All leukemogenic MLL fusion proteins retain the CXXC domain which binds to nonmethylated CpG DNA. We present the solution structure of the MLL CXXC domain in complex with DNA, showing for the first time how the CXXC domain distinguishes nonmethylated from methylated CpG DNA. Based on the structure, we designed point mutations which disrupt DNA binding. Introduction of these mutations into MLL-AF9 results in increased DNA methylation of specific CpG nucleotides in Hoxa9, increased H3K9 methylation, decreased expression of Hoxa9 locus transcripts, loss of immortalization potential, and inability to induce leukemia in mice. These results establish that DNA binding by the CXXC domain and protection against DNA methylation is essential for MLL fusion leukemia. They also provide support for this interaction as a potential target for therapeutic intervention. PMID:20010842

  10. Environmental Aging of Scotch-Weld(TradeMark) AF-555M Structural Adhesive in Composite to Composite Bonds

    NASA Technical Reports Server (NTRS)

    Hou, Tan-Hung; Miner, Gilda A.; Lowther, Sharon E.; Connell, John W.; Baughman, James M.

    2010-01-01

    Fiber reinforced resin matrix composites have found increased usage in recent years. Due to the lack of service history of these relatively new material systems, their long-term aging performance is not well established. In this study, adhesive bonds were prepared by the secondary bonding of Scotch-Weld(TradeMark) AF-555M between pre-cured adherends comprised of T800H/3900-2 uni-directional laminate. The adherends were co-cured with wet peel-ply for surface preparation. Each bond-line of single-lap-shear (SLS) specimen was measured to determine thickness and inspected visually for voids. A three-year environmental aging plan for the SLS specimens at 82 C and 85% relative humidity was initiated. SLS strengths were measured for both controls and aged specimens at room temperature and 82 C. The aging results of strength retention and failure modes to date are reported.

  11. Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.

    PubMed

    Ban, Maria; Booth, David; Heard, Robert; Stewart, Graeme; Goris, An; Vandenbroeck, Koen; Dubois, Bénédicte; Laaksonen, Mikko; Ilonen, Jorma; Alizadeh, Mehdi; Edan, Gilles; Babron, Marie Claude; Brassat, David; Clanet, Michael; Cournu-Rebeix, Isabelle; Fontaine, Bertrand; Semana, Gilbert; Goedde, Rene; Epplen, Jorg; Weber, Alexandra; Infante-Duarte, Carmen; Zipp, Frauke; Rajda, Cecilia; Bencsik, Krisztina; Vécsei, László; Heggarty, Shirley; Graham, Colin; Hawkins, Stanley; Liguori, Maria; Momigliano-Richiardi, Patricia; Caputo, Domenico; Grimaldi, Luigi M E; Leone, Maurizio; Massacesi, Luca; Milanese, Clara; Salvetti, Marco; Savettieri, Giovani; Trojano, Maria; Bielecki, Bartosz; Mycko, Marcin P; Selmaj, Krzysztof; Santos, Monica; Maciel, Patricia; Pereira, Clara; Silva, Ana; Silva, Berta Martins; Coraddu, Francesca; Marrosu, Maria Giovanna; Akesson, Eva; Hillert, Jan; Datta, Pameli; Oturai, Annette; Harbo, Hanne F; Spurkland, Anne; Goertsches, Robert; Villoslada, Pablo; Eraksoy, Mefkure; Hensiek, Anke; Compston, Alastair; Setakis, Efrosini; Gray, Julia; Yeo, Tai Wai; Sawcer, Stephen

    2006-10-01

    By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1. PMID:16934875

  12. Pancreatic cancer

    PubMed Central

    Güngör, C; Hofmann, B T; Wolters-Eisfeld, G; Bockhorn, M

    2014-01-01

    In recent years, it has become clear that the current standard therapeutic options for pancreatic cancer are not adequate and still do not meet the criteria to cure patients suffering from this lethal disease. Although research over the past decade has shown very interesting and promising new therapeutic options for these patients, only minor clinical success was achieved. Therefore, there is still an urgent need for new approaches that deal with early detection and new therapeutic options in pancreatic cancer. To provide optimal care for patients with pancreatic cancer, we need to understand better its complex molecular biology and thus to identify new target molecules that promote the proliferation and resistance to chemotherapy of pancreatic cancer cells. In spite of significant progress in curing cancers with chemotherapy, pancreatic cancer remains one of the most resistant solid tumour cancers and many studies suggest that drug-resistant cancer cells are the most aggressive with the highest relapse and metastatic rates. In this context, activated Notch signalling is strongly linked with chemoresistance and therefore reflects a rational new target to circumvent resistance to chemotherapy in pancreatic cancer. Here, we have focused our discussion on the latest research, current therapy options and recently identified target molecules such as Notch-2 and the heparin-binding growth factor midkine, which exhibit a wide range of cancer-relevant functions and therefore provide attractive new therapeutic target molecules, in terms of pancreatic cancer and other cancers also. Linked Articles This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4 PMID:24024905

  13. Male contraceptive Adjudin is a potential anti-cancer drug

    PubMed Central

    Xie, Qian Reuben; Liu, Yewei; Shao, Jiaxiang; Yang, Jian; Liu, Tengyuan; Zhang, Tingting; Wang, Boshi; Mruk, Dolores D.; Silvestrini, Bruno; Cheng, C. Yan; Xia, Weiliang

    2014-01-01

    Adjudin, also known as AF-2364 and an analog of lonidamine (LND), is a male contraceptive acting through the induction of premature sperm depletion from the seminiferous epithelium when orally administered to adult rats, rabbits or dogs. It is also known that LND can target mitochondria and block energy metabolism in tumor cells. However, whether Adjudin exhibits any anti-cancer activity remains to be elucidated. Herein we described the anti-proliferative activity of Adjudin on cancer cells in vitro and on lung and prostate tumors inoculated in nude mice. We found that Adjudin induced apoptosis in cancer cells through a Caspase-3-dependent pathway. Further experiments revealed that Adjudin could trigger mitochondrial dysfunction in cancer cells, apparently affecting the mitochondrial mass, inducing the loss of mitochondrial membrane potential and reducing cellular ATP levels. Intraperitoneal administration of Adjudin to tumor-bearing athymic nude mice also significantly suppressed the lung and prostate tumor growth. When used in combination with cisplatin, Adjudin enhances the sensitivity to cisplatin-induced cancer cell cytotoxicity. Taken together, these findings have demonstrated that Adjudin may be a potential drug for cancer therapy. PMID:23178657

  14. Time-staggered delivery of docetaxel and H1-S6A,F8A peptide for sequential dual-strike chemotherapy through tumor priming and nuclear targeting.

    PubMed

    Li, Lian; Sun, Wei; Zhang, Zhirong; Huang, Yuan

    2016-06-28

    While highly effective for slowing cancer progression in principle, the c-Myc inhibitor peptide H1-S6A,F8A (H1) has not performed well in tumor studies, in part because it does not pass efficiently through the nuclear envelope. Here we describe a dual-strike strategy in which tumor cells were treated first with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-docetaxel (DTX) conjugates (P-DTX), which arrested cells in the G2/M phase and prolonged the period when the nuclear membrane was disassembled. In the second strike, the cells were then treated with P-H1 conjugates, which entered the nucleus and efficiently inhibited c-Myc. The in vitro studies demonstrated that the combination of P-DTX and P-H1 conjugates was sequence-dependent, and P-DTX followed by P-H1 had synergism, which was significantly more effective than reverse sequential delivery, simultaneous co-delivery or monotherapy with P-DTX or P-H1 alone. The in vivo studies showed that sequential delivery of P-DTX followed by P-H1 remarkably slowed the tumor growth and improved the animal survival. This sequential, dual-strike approach provides new opportunities for nuclear-targeted anticancer drug delivery. PMID:27098443

  15. Characterization of Silver Nanoparticles under Environmentally Relevant Conditions Using Asymmetrical Flow Field-Flow Fractionation (AF4)

    PubMed Central

    Jang, Min-Hee; Lee, Seungho; Hwang, Yu Sik

    2015-01-01

    The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters. PMID:26575993

  16. Characterization of Silver Nanoparticles under Environmentally Relevant Conditions Using Asymmetrical Flow Field-Flow Fractionation (AF4).

    PubMed

    Jang, Min-Hee; Lee, Seungho; Hwang, Yu Sik

    2015-01-01

    The development of methods to monitor manufactured nanomaterials in the environment is one of the crucial areas for the assessment of their risk. More specifically, particle size analysis is a key element, because many properties of nanomaterial are size dependent. The sizing of nanomaterials in real environments is challenging due to their heterogeneity and reactivity with other environmental components. In this study, the fractionation and characterization of a mixture of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) of three different sizes were investigated using asymmetrical flow field-flow fractionation (AF4) coupled with UV-Vis spectrophotometry. In particular, the effects of electrolyte composition and natural organic matter (NOM) on the particle size and stability were evaluated. The fractogram peaks (i.e., stability) of three different AgNPs decreased in the presence of both 10 mM NaCl and 10 mM CaCl2, while increased with increasing concentration of humic acid (HA). In addition, the hydrodynamic diameters of AgNPs in both electrolytes slightly increased with an increase of HA concentration, suggesting the adsorption (coating) of HA onto the particle surface. It is also interesting to note that an increase in the particle size depended on the types of electrolyte, which could be explained by the conformational characteristics of the adsorbed HA layers. Consistent these results, AgNPs suspended in lake water containing relatively high concentration of organic carbon (TOC) showed higher particle stability and larger particle size (i.e., by approximately 4 nm) than those in river water. In conclusion, the application of AF4 coupled with highly sensitive detectors could be a powerful method to characterize nanoparticles in natural waters. PMID:26575993

  17. Degree of Recruitment of DOT1L to MLL-AF9 Defines Level of H3K79 Di- and Tri-methylation on Target Genes and Transformation Potential

    PubMed Central

    Kuntimaddi, Aravinda; Achille, Nicholas J.; Thorpe, Jeremy; Lokken, Alyson A.; Singh, Ritambhara; Hemenway, Charles S.; Adli, Mazhar; Zeleznik-Le, Nancy J.; Bushweller, John H.

    2015-01-01

    SUMMARY The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemia has a consistently poor outcome. One of the most common translocation partners is AF9 (MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcription. We show that DOT1L has three AF9 binding sites, and present the NMR solution structure of a DOT1L-AF9 complex. We generate structure-guided point mutations and find they have graded effects on recruitment of DOT1L to MLL-AF9. ChIP-Seq analyses of H3K79me2 and H3K79me3 show that graded reduction of the DOT1L interaction with MLL-AF9 results in differential loss of H3K79me2 and me3 at MLL-AF9 target genes. Furthermore, the degree of DOT1L recruitment is linked to the level of MLL-AF9 hematopoietic transformation. PMID:25921540

  18. Contagious cancer.

    PubMed

    Welsh, James S

    2011-01-01

    Although cancer can on occasion be caused by infectious agents such as specific bacteria, parasites, and viruses, it is not generally considered a transmissible disease. In rare circumstances, however, direct communication from one host to another has been documented. The Tasmanian devil is now threatened with extinction in the wild because of a fatal transmissible cancer, devil facial tumor disease (DFTD). Another example is canine transmissible venereal tumor (CTVT or Sticker's sarcoma) in dogs. There is a vast difference in prognosis between these two conditions. DFTD is often fatal within 6 months, whereas most cases of CTVT are eventually rejected by the host dog, who then is conferred lifelong immunity. In man, only scattered case reports exist about such communicable cancers, most often in the setting of organ or hematopoietic stem cell transplants and cancers arising during pregnancy that are transmitted to the fetus. In about one third of cases, transplant recipients develop cancers from donor organs from individuals who were found to harbor malignancies after the transplantation. The fact that two thirds of the time cancer does not develop, along with the fact that cancer very rarely is transmitted from person to person, supports the notion that natural immunity prevents such cancers from taking hold in man. These observations might hold invaluable clues to the immunobiology and possible immunotherapy of cancer. PMID:21212437

  19. Lung Cancer Screening

    MedlinePlus

    ... Cancer Treatment Small Cell Lung Cancer Treatment Lung cancer is the leading cause of cancer death in the United States. Lung cancer is ... non- skin cancer in the United States. Lung cancer is the leading cause of cancer death in men and in women. ...

  20. Uterine Cancer: Cancer of the Uterus

    MedlinePlus

    ... sheet ePublications Uterine cancer: Cancer of the uterus fact sheet Print this fact sheet Uterine cancer: Cancer ... U.S. federal government and is in the public domain. This public information is not copyrighted and may ...

  1. Cancer in Patients With Gabapentin (GPRD)

    ClinicalTrials.gov

    2012-02-02

    Pain, Neuropathic; Epilepsy; Renal Pelvis Cancer; Pancreatic Cancer; Breast Cancer; Nervous System Cancer; Chronic Pancreatitis; Stomach Cancer; Renal Cell Carcinoma; Diabetes; Bladder Cancer; Bone and Joint Cancer; Penis Cancer; Anal Cancer; Cancer; Renal Cancer

  2. Effect of Long-Term Dietary Arginyl-Fructose (AF) on Hyperglycemia and HbA1c in Diabetic db/db Mice

    PubMed Central

    Lee, Kwang-Hyoung; Ha, Kyoung-Soo; Jo, Sung-Hoon; Lee, Chong M.; Kim, Young-Cheul; Chung, Kwang-Hoe; Kwon, Young-In

    2014-01-01

    We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF) lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch) with and without AF (4% in the diet) for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001) and body weight (p < 0.001). The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001). Dietary treatment of acarbose® (0.04% in diet), a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level. PMID:24823880

  3. Exploring the mechanism how AF9 recognizes and binds H3K9ac by molecular dynamics simulations and free energy calculations.

    PubMed

    Wang, Quan; Zheng, Qing-Chuan; Zhang, Hong-Xing

    2016-11-01

    Histone acetylation is a very important regulatory mechanism in gene expression in the chromatin context. A new protein family-YEATS domains have been found as a novel histone acetylation reader, which could specific recognize the histone lysine acetylation. AF9 is an important one in the YEATS family. Focused on the AF9-H3K9ac (K9 acetylation) complex (ALY) (PDB code: 4TMP) and a serials of mutants, MUT (the acetyllsine of H3K9ac was mutated to lysine), F59A, G77A, and D103A, we applied molecular dynamics simulation and molecular mechanics Poisson-Boltzmann (MM-PBSA) free energy calculations to examine the role of AF9 protein in recognition interaction. The simulation results and analysis indicate that some residues of the protein have significant influence on recognition and binding to H3K9ac peptides and hydrophobic surface show the hydrophobic interactions play an important role in the binding. Our work can give important information to understand how the protein AF9 recognizes the peptides H3K9ac. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 779-786, 2016. PMID:27312527

  4. Inactive allele-specific methylation and chromatin structure of the imprinted gene U2af1-rs1 on mouse chromosome 11

    SciTech Connect

    Shibata, Hideo; Yoshino, Kiyoshi; Kamiya, Mamoru

    1996-07-01

    The imprinted U2Af1-rs1 gene that maps to mouse chromosome 11 is predominately expressed from the paternal allele. We examined the methylation of genomic sequences in and around the U2af1-rs1 locus to establish the extent of sequence modifications that accompanied the silencing of the maternal allele. The analysis of HapII or HhaI sites showed that the silent maternal allele was hypermethylated in a block of CpG sequences that covered more than 10 kb. By comparison, the expressed paternal allele was unmethylated from a CpG island upstream of the transcribed region through 2 kb. An analysis of DNaseI hypersensitivity of a putative promoter of U2af1-rs1 showed an open chromatin conformation only on the unmethylated, expressed paternal allele. These results suggest that allele-specific hypermethylation covering the gene and its upstream CpG island plays a role in maternal allele repression of U2af1-rs1, which is reflected in altered chromatin conformation of DNaseI hypersensitive sites. 9 refs., 2 figs.

  5. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.

    PubMed Central

    Le Douarin, B; Zechel, C; Garnier, J M; Lutz, Y; Tora, L; Pierrat, P; Heery, D; Gronemeyer, H; Chambon, P; Losson, R

    1995-01-01

    Nuclear receptors (NRs) bound to response elements mediate the effects of cognate ligands on gene expression. Their ligand-dependent activation function, AF-2, presumably acts on the basal transcription machinery through intermediary proteins/mediators. We have isolated a mouse nuclear protein, TIF1, which enhances RXR and RAR AF-2 in yeast and interacts in a ligand-dependent manner with several NRs in yeast and mammalian cells, as well as in vitro. Remarkably, these interactions require the amino acids constituting the AF-2 activating domain conserved in all active NRs. Moreover, the oestrogen receptor (ER) AF-2 antagonist hydroxytamoxifen cannot promote ER-TIF1 interaction. We propose that TIF1, which contains several conserved domains found in transcriptional regulatory proteins, is a mediator of ligand-dependent AF-2. Interestingly, the TIF1 N-terminal moiety is fused to B-raf in the mouse oncoprotein T18. Images PMID:7744009

  6. Stomach (Gastric) Cancer Screening

    MedlinePlus

    ... Treatment Stomach Cancer Prevention Stomach Cancer Screening Research Stomach (Gastric) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Stomach (Gastric) Cancer Key Points Stomach cancer is a ...

  7. Breast Cancer Overview

    MedlinePlus

    ... Breast Cancer - Overview Request Permissions Print to PDF Breast Cancer - Overview Approved by the Cancer.Net Editorial Board , ... bean-shaped organs that help fight infection. About breast cancer Cancer begins when healthy cells in the breast ...

  8. Types of Breast Cancers

    MedlinePlus

    ... the key statistics about breast cancer? Types of breast cancers Breast cancer can be separated into different types ... than invasive ductal carcinoma. Less common types of breast cancer Inflammatory breast cancer This uncommon type of invasive ...

  9. Children's cancer centers

    MedlinePlus

    Pediatric cancer center; Pediatric oncology center; Comprehensive cancer center ... Treating childhood cancer is not the same as treating adult cancer. The cancers are different. So are the treatments and the ...

  10. Photodynamic therapy for cancer

    MedlinePlus

    ... Cancer of the esophagus-photodynamic; Esophageal cancer-photodynamic; Lung cancer-photodynamic ... the light at the cancer cells. PDT treats cancer in the: Lungs, using a bronchoscope Esophagus, using upper endoscopy Doctors ...

  11. What Is Ovarian Cancer?

    MedlinePlus

    ... the key statistics about ovarian cancer? What is ovarian cancer? Cancer starts when cells in the body begin ... section . Other cancers that are similar to epithelial ovarian cancer Primary peritoneal carcinoma Primary peritoneal carcinoma (PPC) is ...

  12. Living with Prostate Cancer

    MedlinePlus

    ... pork, lamb, and processed meat (such as hot dogs, sausage, and bacon); and low in high-fat ... ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects Cancer ...

  13. What Is Bone Cancer?

    MedlinePlus

    ... our document called Osteosarcoma . Chondrosarcoma: Chondrosarcoma (KON-droh-sar-KOH-muh) is a cancer of cartilage cells. ... AdditionalResources Other Resources and References Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & ...

  14. Tests for Liver Cancer

    MedlinePlus

    ... cancer Next Topic Liver cancer stages Tests for liver cancer If you have some of the signs ... cancer has come back (recurred). Other blood tests Liver function tests (LFTs): Because liver cancer often develops ...

  15. Basic Cancer Terms

    MedlinePlus

    ... Statistics Cancer Terms: Treatment Cancer Terms: After Treatment Online Medical Dictionaries Diagnosing Cancer Managing Your Care Financial Considerations How Cancer is Treated Side Effects Dating, Sex, and Reproduction Advanced Cancer For Children For ...

  16. Cancer Terms: After Treatment

    MedlinePlus

    ... Statistics Cancer Terms: Treatment Cancer Terms: After Treatment Online Medical Dictionaries Diagnosing Cancer Managing Your Care Financial Considerations How Cancer is Treated Side Effects Dating, Sex, and Reproduction Advanced Cancer For Children For ...

  17. What Is Lung Cancer?

    MedlinePlus

    ... starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may spread ... lung cancer. For more information, visit the National Cancer Institute’s Lung Cancer. Previous Basic Information Basic Information Basic Information ...

  18. Photodynamic therapy for cancer

    MedlinePlus

    ... Photoradiation therapy; Cancer of the esophagus-photodynamic; Esophageal cancer-photodynamic; Lung cancer-photodynamic ... the light at the cancer cells. PDT treats cancer in the: Lungs, using a bronchoscope Esophagus, using upper endoscopy Doctors ...

  19. B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies

    PubMed Central

    Sinner, Moritz F.; Stepas, Katherine A.; Moser, Carlee B.; Krijthe, Bouwe P.; Aspelund, Thor; Sotoodehnia, Nona; Fontes, João D.; Janssens, A. Cecile J.W.; Kronmal, Richard A.; Magnani, Jared W.; Witteman, Jacqueline C.; Chamberlain, Alanna M.; Lubitz, Steven A.; Schnabel, Renate B.; Vasan, Ramachandran S.; Wang, Thomas J.; Agarwal, Sunil K.; McManus, David D.; Franco, Oscar H.; Yin, Xiaoyan; Larson, Martin G.; Burke, Gregory L.; Launer, Lenore J.; Hofman, Albert; Levy, Daniel; Gottdiener, John S.; Kääb, Stefan; Couper, David; Harris, Tamara B.; Astor, Brad C.; Ballantyne, Christie M.; Hoogeveen, Ron C.; Arai, Andrew E.; Soliman, Elsayed Z.; Ellinor, Patrick T.; Stricker, Bruno H.C.; Gudnason, Vilmundur; Heckbert, Susan R.; Pencina, Michael J.; Benjamin, Emelia J.; Alonso, Alvaro

    2014-01-01

    Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56–1.76], P < 0.0001 and 1.18 (95% CI, 1.11–1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ2 = 17.0; CRP, χ2 = 10.5; BNP and CRP, χ2 = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022–0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322–0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers. PMID:25037055

  20. Device-detected atrial fibrillation and risk for stroke: an analysis of >10 000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices)

    PubMed Central

    Boriani, Giuseppe; Glotzer, Taya V.; Santini, Massimo; West, Teena M.; De Melis, Mirko; Sepsi, Milan; Gasparini, Maurizio; Lewalter, Thorsten; Camm, John A.; Singer, Daniel E.

    2014-01-01

    Objective The aim of this study was to assess the association between maximum daily atrial fibrillation (AF) burden and risk of ischaemic stroke. Background Cardiac implanted electronic devices (CIEDs) enhance detection of AF, providing a comprehensive measure of AF burden. Design, setting, and patients A pooled analysis of individual patient data from five prospective studies was performed. Patients without permanent AF, previously implanted with CIEDs, were included if they had at least 3 months of follow-up. A total of 10 016 patients (median age 70 years) met these criteria. The risk of ischaemic stroke associated with pre-specified cut-off points of AF burden (5 min, 1, 6, 12, and 23 h, respectively) was assessed. Results During a median follow-up of 24 months, 43% of 10 016 patients experienced at least 1 day with at least 5 min of AF burden and for them the median time to the maximum AF burden was 6 months (inter-quartile range: 1.3–14). A Cox regression analysis adjusted for the CHADS2 score and anticoagulants at baseline demonstrated that AF burden was an independent predictor of ischaemic stroke. Among the thresholds of AF burden that we evaluated, 1 h was associated with the highest hazard ratio (HR) for ischaemic stroke, i.e. 2.11 (95% CI: 1.22–3.64, P = 0.008). Conclusions Device-detected AF burden is associated with an increased risk of ischaemic stroke in a relatively unselected population of CIEDs patients. This finding may add to the basis for timely and clinically appropriate decision-making on anticoagulation treatment. PMID:24334432

  1. Differential recognition of the polypyrimidine-tract by the general splicing factor U2AF65 and the splicing repressor sex-lethal.

    PubMed Central

    Singh, R; Banerjee, H; Green, M R

    2000-01-01

    The polypyrimidine-tract (Py-tract) adjacent to 3' splice sites is an essential splicing signal and is recognized by several proteins, including the general splicing factor U2AF65 and the highly specific splicing repressor Sex-lethal (SXL). They both contain ribonucleoprotein-consensus RNA-binding motifs. However, U2AF65 recognizes a wide variety of Py-tracts, whereas SXL recognizes specific Py-tracts such as the nonsex-specific Py-tract of the transformer pre-mRNA. It is not understood how these seemingly similar proteins differentially recognize the Py-tract. To define these interactions, we used chemical interference and protection assays, saturation mutagenesis, and RNAs containing modified nucleotides. We find that these proteins recognize distinct features of the RNA. First, although uracils within the Py-tract are protected from chemical modification by both of these proteins, modification of any one of seven uracils by hydrazine, or any of eight phosphates by ethylnitrosourea strongly interfered with the binding of SXL only. Second, the 2' hydroxyl groups or backbone conformation appeared important for the binding of SXL, but not U2AF65. Third, although any of the bases (cytosine >> adenine > guanine) could substitute for uracils for U2AF65 binding, only guanine partially substituted for certain uracils for SXL binding. The different dependence on individual contacts and nucleotide preference may provide a basis for the different RNA-binding specificities and thus functions of U2AF65 and SXL in 3' splice site choice. PMID:10864047

  2. Oral Cancer

    MedlinePlus

    ... What are the effects of oral cancer on speech and swallowing? The effects of cancer on speech and swallowing depend on the location and size ... movement. This could result in unclear production of speech sounds made with the lips such as /p/, / ...

  3. Vulvar Cancer

    MedlinePlus

    ... sex painful and difficult. If found early, vulvar cancer has a high cure rate and the treatment options involve less surgery. ... people may also need radiation therapy. When vulvar cancer is found and treated early, the cure rate is over 90%. The key to a ...

  4. Oral Cancer

    MedlinePlus

    ... won't heal Bleeding in your mouth Loose teeth Problems or pain with swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  5. Stomach cancer

    MedlinePlus

    ... much higher than in the United States. The value of screening in the United States and other countries with much lower rates of stomach cancer is not clear. The following may help reduce your risk of stomach cancer: DO NOT smoke. Keep a ...

  6. Breast Cancer

    MedlinePlus

    ... I found something when I did my breast self-exam. What should I do now? How often should I have mammograms? I have breast cancer. What are my treatment options? How often should I do breast self-exams? I have breast cancer. Is my daughter ...

  7. Intestinal Cancer

    MedlinePlus

    ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason Blood in the stool A lump in the abdomen Imaging tests that create pictures of the small ... help diagnose intestinal cancer and show whether it has spread. Surgery is ...

  8. Anal cancer

    MedlinePlus

    ... the last part of your large intestine where solid waste from food (stool) is stored. Stool leaves your body through the anus when you have a bowel movement. Anal cancer is fairly rare. It spreads ... Squamous cell carcinoma. This is the most common type of anal cancer. It starts in cells that ...

  9. Gallbladder cancer

    PubMed Central

    Patrlj, Leonardo; Kopljar, Mario; Kliček, Robert; Kolovrat, Marijan; Loncar, Bozo; Busic, Zeljko

    2014-01-01

    Gallbladder cancer is the fifth most common cancer involving gastrointestinal tract, but it is the most common malignancy of the biliary tract, accounting for 80-95% of biliary tract cancers. This tumor is a highly lethal disease with an overall 5-year survival of less than 5% and mean survival mere than 6 months. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. Patients with preoperative suspicion of gallbladder cancer should not be treated by laparoscopy. Epidemiological studies have identified striking geographic and ethnic disparities—inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Improved imaging modalities and improved radical aggressive surgical approach in the last decade has improved outcomes and helped prolong survival in patients with gallbladder cancer. The overall 5-year survival for patients with gallbladder cancer who underwent R0 curative resection was from 21% to 69%. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract. PMID:25392833

  10. Prostate Cancer Research Trial Helps John Spencer Treat His Cancer

    MedlinePlus

    ... please turn Javascript on. Feature: Prostate Cancer Prostate Cancer Research Trial Helps John Spencer Treat His Cancer Past ... Prostate Cancer" Articles Progress Against Prostate Cancer / Prostate Cancer Research Trial Helps John Spencer Treat His Cancer / Prostate ...

  11. Ovarian cancer.

    PubMed

    Matulonis, Ursula A; Sood, Anil K; Fallowfield, Lesley; Howitt, Brooke E; Sehouli, Jalid; Karlan, Beth Y

    2016-01-01

    Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. PMID:27558151

  12. Pancreatic cancer.

    PubMed

    Kamisawa, Terumi; Wood, Laura D; Itoi, Takao; Takaori, Kyoichi

    2016-07-01

    Pancreatic cancer is a highly lethal disease, for which mortality closely parallels incidence. Most patients with pancreatic cancer remain asymptomatic until the disease reaches an advanced stage. There is no standard programme for screening patients at high risk of pancreatic cancer (eg, those with a family history of pancreatic cancer and chronic pancreatitis). Most pancreatic cancers arise from microscopic non-invasive epithelial proliferations within the pancreatic ducts, referred to as pancreatic intraepithelial neoplasias. There are four major driver genes for pancreatic cancer: KRAS, CDKN2A, TP53, and SMAD4. KRAS mutation and alterations in CDKN2A are early events in pancreatic tumorigenesis. Endoscopic ultrasonography and endoscopic ultrasonography-guided fine-needle aspiration offer high diagnostic ability for pancreatic cancer. Surgical resection is regarded as the only potentially curative treatment, and adjuvant chemotherapy with gemcitabine or S-1, an oral fluoropyrimidine derivative, is given after surgery. FOLFIRINOX (fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) are the treatments of choice for patients who are not surgical candidates but have good performance status. PMID:26830752

  13. Breast Cancer -- Male

    MedlinePlus

    ... Home > Types of Cancer > Breast Cancer in Men Breast Cancer in Men This is Cancer.Net’s Guide to Breast Cancer in Men. Use the menu below to choose ... social workers, and patient advocates. Cancer.Net Guide Breast Cancer in Men Overview Statistics Risk Factors and Prevention ...

  14. Prostate cancer.

    PubMed

    Attard, Gerhardt; Parker, Chris; Eeles, Ros A; Schröder, Fritz; Tomlins, Scott A; Tannock, Ian; Drake, Charles G; de Bono, Johann S

    2016-01-01

    Much progress has been made in research for prostate cancer in the past decade. There is now greater understanding for the genetic basis of familial prostate cancer with identification of rare but high-risk mutations (eg, BRCA2, HOXB13) and low-risk but common alleles (77 identified so far by genome-wide association studies) that could lead to targeted screening of patients at risk. This is especially important because screening for prostate cancer based on prostate-specific antigen remains controversial due to the high rate of overdiagnosis and unnecessary prostate biopsies, despite evidence that it reduces mortality. Classification of prostate cancer into distinct molecular subtypes, including mutually exclusive ETS-gene-fusion-positive and SPINK1-overexpressing, CHD1-loss cancers, could allow stratification of patients for different management strategies. Presently, men with localised disease can have very different prognoses and treatment options, ranging from observation alone through to radical surgery, with few good-quality randomised trials to inform on the best approach for an individual patient. The survival of patients with metastatic prostate cancer progressing on androgen-deprivation therapy (castration-resistant prostate cancer) has improved substantially. In addition to docetaxel, which has been used for more than a decade, in the past 4 years five new drugs have shown efficacy with improvements in overall survival leading to licensing for the treatment of metastatic castration-resistant prostate cancer. Because of this rapid change in the therapeutic landscape, no robust data exist to inform on the selection of patients for a specific treatment for castration-resistant prostate cancer or the best sequence of administration. Moreover, the high cost of the newer drugs limits their widespread use in several countries. Data from continuing clinical and translational research are urgently needed to improve, and, crucially, to personalise management. PMID

  15. Risks of Breast Cancer Screening

    MedlinePlus

    ... of Breast & Gynecologic Cancers Breast Cancer Screening Research Breast Cancer Screening (PDQ®)–Patient Version What is screening? Go ... cancer screening: Cancer Screening Overview General Information About Breast Cancer Key Points Breast cancer is a disease in ...

  16. Risks of Endometrial Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  17. Risks of Prostate Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  18. Risks of Cervical Cancer Screening

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Centers Frederick National Lab Partners & Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer ...

  19. Lung cancer

    PubMed Central

    Dong, Jie; Kislinger, Thomas; Jurisica, Igor; Wigle, Dennis A.

    2010-01-01

    High-throughput genomic data for both lung development and lung cancer continue to accumulate. Significant molecular intersection between these two processes has been hypothesized due to overlap in phenotypes and genomic variation. Examining the network biology of both cancer and development of the lung may shed functional light on the individual signaling modules involved. Stem cell biology may explain a portion of this network intersection and consequently studying lung organogenesis may have relevance for understanding lung cancer. This review summarizes our understanding of the potential overlapping mechanisms involved in lung development and lung tumorigenesis. PMID:19202349

  20. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

    SciTech Connect

    Fujiki, Atsushi; Imamura, Toshihiko; Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya; Sugita, Kanji; Hosoi, Hajime

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein {alpha} (C/EBP{alpha}) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  1. Cancer Genetics Services Directory

    MedlinePlus

    ... Overview–for health professionals Research NCI Cancer Genetics Services Directory This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic ...

  2. Screening Education And Recognition in Community pHarmacies of Atrial Fibrillation to prevent stroke in an ambulant population aged ≥65 years (SEARCH-AF stroke prevention study): a cross-sectional study protocol

    PubMed Central

    Freedman, Saul Benedict; Redfern, Julie; McLachlan, Andrew; Krass, Ines; Bennett, Alexandra; Briffa, Thomas; Bauman, Adrian; Neubeck, Lis

    2012-01-01

    Background Atrial fibrillation (AF) is associated with a high risk of stroke and may often be asymptomatic. AF is commonly undiagnosed until patients present with sequelae, such as heart failure and stroke. Stroke secondary to AF is highly preventable with the use of appropriate thromboprophylaxis. Therefore, early identification and appropriate evidence-based management of AF could lead to subsequent stroke prevention. This study aims to determine the feasibility and impact of a community pharmacy-based screening programme focused on identifying undiagnosed AF in people aged 65 years and older. Methods and analysis This cross-sectional study of community-based screening to identify undiagnosed AF will evaluate the feasibility of screening for AF using a pulse palpation and handheld single-lead electrocardiograph (ECG) device. 10 community pharmacies will be recruited and trained to implement the screening protocol, targeting a total of 1000 participants. The primary outcome is the proportion of people newly identified with AF at the completion of the screening programme. Secondary outcomes include level of agreement between the pharmacist's and the cardiologist's interpretation of the single-lead ECG; level of agreement between irregular rhythm identified with pulse palpation and with the single-lead ECG. Process outcomes related to sustainability of the screening programme beyond the trial setting, pharmacist knowledge of AF and rate of uptake of referral to full ECG evaluation and cardiology review will also be collected. Ethics and dissemination Primary ethics approval was received on 26 March 2012 from Sydney Local Health District Human Research Ethics Committee—Concord Repatriation General Hospital zone. Results will be disseminated via forums including, but not limited to, peer-reviewed publication and presentation at national and international conferences. Clinical trials registration number ACTRN12612000406808. PMID:22734120

  3. Metastatic Cancer

    MedlinePlus

    ... Cancer.gov en español Multimedia Publications Site Map Digital Standards for NCI Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department of Health ...

  4. Endometrial Cancer

    MedlinePlus

    Member Login Join Pay Dues Follow us: Women's Health Care Physicians Contact Us My ACOG ACOG Departments Donate ... and is best made in consultation with your health care team. What happens after treatment for endometrial cancer? ...

  5. Cancer Clusters

    MedlinePlus

    ... Resources NCI Grants Management Legal Requirements NCI Grant Policies Grants Management Contacts Training Cancer Training at NCI Funding for ... Closeout NCI Grants Management Legal Requirements NCI Grant Policies Grant Management Contacts Other Funding Find NCI funding for small ...

  6. Childhood Cancer

    MedlinePlus

    ... the circulatory system and the lymphatic system , two systems that are located throughout the body. This makes it hard to treat these cancers by operating on just one area. However, in children with ...

  7. Oral cancer

    MedlinePlus

    ... is advanced Other symptoms may include: Chewing problems Mouth sores that may bleed Pain with swallowing Speech difficulties ... Your doctor or dentist will examine your mouth area. The exam may ... bleeding Tests used to confirm oral cancer include: Gum biopsy ...

  8. Thyroid cancer

    MedlinePlus

    ... known prevention. Awareness of risk (such as previous radiation therapy to the neck) can allow earlier diagnosis and treatment. Sometimes, people with family histories and genetic mutations related to thyroid cancer will have their thyroid ...

  9. Endometrial Cancer

    MedlinePlus

    ... having diabetes. Using estrogen replacement therapy without taking progestin may also increase the risk for endometrial cancer. ... take a combination of estrogen and the hormone progestin. While estrogen stimulates growth of the endometrium, progestin ...

  10. Breast cancer

    MedlinePlus

    ... chance that you could develop breast cancer: Some risk factors you can control, such as drinking alcohol. Others, such as family history, you cannot control. The more risk factors you have, the more your risk increases. ...

  11. Endometrial cancer

    MedlinePlus

    ... Endometrial biopsy Dilation and curettage ( D and C ) Pap smear (may raise a suspicion for endometrial cancer, but ... for more than 2 years. Frequent pelvic exams, Pap smears and endometrial biopsy may be considered in some ...

  12. Cancer Imaging

    MedlinePlus

    ... I/II Trials CIP ARRA-Funded Clinical Trials Informatics The Cancer Imaging Archive TCGA Imaging Genomics Quantitative Imaging Network LIDC-IDRI Imaging Informatics Resources News & Events News and Announcements Events – Meetings ...

  13. Cervical cancer

    MedlinePlus

    ... eye. Special tests and tools are needed to spot such conditions: A Pap smear screens for precancers and cancer, but does not make a final diagnosis. The human papillomavirus (HPV) DNA test may be ...

  14. Lung cancer

    MedlinePlus

    ... any symptoms. Symptoms depend on the type of cancer you have, but may include: Chest pain Cough that does not go away Coughing up blood Fatigue Losing weight without trying Loss of appetite Shortness of breath ...

  15. Vulvar Cancer

    MedlinePlus

    ... a human papillomavirus (HPV) infection or have a history of genital warts. Your health care provider diagnoses vulvar cancer with a physical exam and a biopsy. Treatment varies, depending on your overall health and ...

  16. Aging, cancer, and cancer vaccines

    PubMed Central

    2012-01-01

    World population has experienced continuous growth since 1400 A.D. Current projections show a continued increase - but a steady decline in the population growth rate - with the number expected to reach between 8 and 10.5 billion people within 40 years. The elderly population is rapidly rising: in 1950 there were 205 million people aged 60 or older, while in 2000 there were 606 million. By 2050, the global population aged 60 or over is projected to expand by more than three times, reaching nearly 2 billion people [1]. Most cancers are age-related diseases: in the US, 50% of all malignancies occur in people aged 65-95. 60% of all cancers are expected to be diagnosed in elderly patients by 2020 [2]. Further, cancer-related mortality increases with age: 70% of all malignancy-related deaths are registered in people aged 65 years or older [3]. Here we introduce the microscopic aspects of aging, the pro-inflammatory phenotype of the elderly, and the changes related to immunosenescence. Then we deal with cancer disease and its development, the difficulty of treatment administration in the geriatric population, and the importance of a comprehensive geriatric assessment. Finally, we aim to analyze the complex interactions of aging with cancer and cancer vaccinology, and the importance of this last approach as a complementary therapy to different levels of prevention and treatment. Cancer vaccines, in fact, should at present be recommended in association to a stronger cancer prevention and conventional therapies (surgery, chemotherapy, radiation therapy), both for curative and palliative intent, in order to reduce morbidity and mortality associated to cancer progression. PMID:22510392

  17. Prostate cancer.

    PubMed

    Castillejos-Molina, Ricardo Alonso; Gabilondo-Navarro, Fernando Bernardo

    2016-04-01

    Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by prostate biopsy in patients with abnormalities detected in their prostate-specific antigen (PSA) levels or digital rectal exam (DRE). This article reviews screening and diagnostic methods as well as treatment options for patients diagnosed with prostate cancer. PMID:27557386

  18. Rhizovarins A-F, Indole-Diterpenes from the Mangrove-Derived Endophytic Fungus Mucor irregularis QEN-189.

    PubMed

    Gao, Shu-Shan; Li, Xiao-Ming; Williams, Katherine; Proksch, Peter; Ji, Nai-Yun; Wang, Bin-Gui

    2016-08-26

    Genome mining of the fungus Mucor irregularis (formerly known as Rhizomucor variabilis) revealed the presence of various gene clusters for secondary metabolite biosynthesis, including several terpene-based clusters. Investigation into the chemical diversity of M. irregularis QEN-189, an endophytic fungus isolated from the fresh inner tissue of the marine mangrove plant Rhizophora stylosa, resulted in the discovery of 20 structurally diverse indole-diterpenes including six new compounds, namely, rhizovarins A-F (1-6). Among them, compounds 1-3 represent the most complex members of the reported indole-diterpenes. The presence of an unusual acetal linked to a hemiketal (1) or a ketal (2 and 3) in an unprecedented 4,6,6,8,5,6,6,6,6-fused indole-diterpene ring system makes them chemically unique. Their structures and absolute configurations were elucidated by spectroscopic analysis, modified Mosher's method, and chemical calculations. Each of the isolated compounds was evaluated for antitumor activity against HL-60 and A-549 cell lines. PMID:27462726

  19. Distribution and preliminary exposure assessment of bisphenol AF (BPAF) in various environmental matrices around a manufacturing plant in China.

    PubMed

    Song, Shanjun; Ruan, Ting; Wang, Thanh; Liu, Runzeng; Jiang, Guibin

    2012-12-18

    Increasing attention has been paid to bisphenol A and bisphenol (BP) analogues due to high production volumes, wide usage and potential adverse effects. Bisphenol AF (BPAF) is considered a new bisphenol analogue which is used as raw material in plastic industry, but little is known about its occurrence in the environment and the potential associated risk. In this work, BPAF levels and environmental distribution were reported in samples collected around a manufacturing plant and a preliminary exposure risk assessment to local residents was conducted. BPAF was detected in most of the samples, with levels in river ranging between

  20. Enhanced removal of bisphenol-AF onto chitosan-modified zeolite by sodium cholate in aqueous solutions.

    PubMed

    Peng, Sha; Hao, Kunyan; Han, Feng; Tang, Zheng; Niu, Beibei; Zhang, Xu; Wang, Zhen; Hong, Song

    2015-10-01

    The removal of bisphenol-AF (BPAF) from aqueous solutions onto chitosan-modified zeolite (Ch-Z) in the absence and presence of sodium cholate (NaC) was investigated. It was found that NaC significantly increased the adsorption capacity of Ch-Z for BPAF. At an initial concentration of 100 μmol/L, the removal of BPAF by adsorption onto Ch-Z with NaC was more than ninefold higher than without NaC, and the maximum removal was achieved at a Ch-Z dosage of 1g/L with a NaC concentration of 1.68 mmol/L. Besides, batch studies were performed to evaluate the effects of various experimental parameters on the removal of BPAF. Kinetic studies and adsorption isotherms indicated that the adsorption process of BPAF onto Ch-Z with NaC could be expressed by a pseudo second-order model and the Freundlich isotherm model, respectively. For the enhanced removal, an interaction mechanism was proposed involving the co-effect of BPAF and NaC adsorbed onto Ch-Z. PMID:26076637