Sample records for lead 199

  1. F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability.

    PubMed

    Kang, Jingjing; Gao, Jie; Yao, Wenwu; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Yao, Jiahao; Xin, Wenwen; Zhao, Baohua; Wang, Jinglin

    2017-07-03

    Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETX F199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETX F199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca 2+ release from intracellular Ca 2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETX F199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins.

  2. F199E substitution reduced toxicity of Clostridium perfringens epsilon toxin by depriving the receptor binding capability

    PubMed Central

    Kang, Jingjing; Gao, Jie; Yao, Wenwu; Kang, Lin; Gao, Shan; Yang, Hao; Ji, Bin; Li, Ping; Liu, Jing; Yao, Jiahao; Xin, Wenwen; Zhao, Baohua; Wang, Jinglin

    2017-01-01

    ABSTRACT Epsilon toxin (ETX), a potent toxin, is produced by types B and D strains of Clostridium perfringens, which could cause severe diseases in humans and domestic animals. Mutant rETXF199E was previously demonstrated to be a good vaccine candidate. However, the mechanism concerned remains unknown. To clarify how F199E substitution reduced ETX toxicity, we performed a series of experiments. The results showed that the cell-binding and pore-forming ability of rETXF199E was almost abolished. We speculated that F199E substitution reduced toxicity by depriving the receptor binding capability of ETX, which contributed to the hypothesis that domain I of ETX is responsible for cell binding. In addition, our data suggested that ETX could cause Ca2+ release from intracellular Ca2+ stores, which may underlie an alternate pathway leading to cell death. Furthermore, ETX induced crenation of the MDCK cells was observed, with sags and crests first appearing on the surface of condensed MDCK cells, according to scanning electron microscopy. The data also demonstrated the safety and potentiality of rETXF199E as a vaccine candidate for humans. In summary, findings of this work potentially contribute to a better understanding of the pathogenic mechanism of ETX and the development of vaccine against diseases caused by ETX, using mutant proteins. PMID:28304231

  3. Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling.

    PubMed

    Shen, Zhan-Long; Wang, Bo; Jiang, Ke-Wei; Ye, Chun-Xiang; Cheng, Cheng; Yan, Yi-Chao; Zhang, Ji-Zhun; Yang, Yang; Gao, Zhi-Dong; Ye, Ying-Jiang; Wang, Shan

    2016-06-07

    The progression of distant metastasis cascade is a multistep and complicated process, frequently leading to a poor prognosis in cancer patients. Recently, growing evidence has indicated that deregulation of microRNAs (miRNAs) contributes to tumorigenesis and tumor progression in colorectal cancer (CRC). In the present study, by comparing the miRNA expression profiles of CRC tissues and corresponding hepatic metastasis tissues, we established the downregulation of miR-199b in CRC metastasis tissues. The decrease in miR-199b expression was significantly correlated to late TNM stage and distant metastasis. Moreover, Kaplan-Meier curves showed that CRC patients with high expression level of miR-199b had a longer median survival. Functional assays results indicated that the restoration of miR-199b considerably reduced cell invasion and migration in vitro and in vivo, and increased the sensitivity to 5-FU and oxaliplatin. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-199b in CRC. The expression of miR-199b was inversely correlated with SIRT1 in CRC specimens. SIRT1 knockdown produced effects on biological behavior that were similar to those of miR-199b overexpression. Furthermore, through Human Tumor Metastasis PCR Array we discovered KISS1 was one of the downstream targets of SIRT1. Silencing of SIRT1 upregulated KISS1 expression by enhancing the acetylation of the transcription factor CREB. The latter was further activated via binding to the promoter of KISS1 to induce transcription. Thus, we concluded that miR-199b regulates SIRT1/CREB/KISS1 signaling pathway and might serve as a prognosis marker or a novel therapeutic target for patients with CRC.

  4. mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability.

    PubMed

    Mayer, Christine; Zhao, Jian; Yuan, Xuejun; Grummt, Ingrid

    2004-02-15

    In cycling cells, transcription of ribosomal RNA genes by RNA polymerase I (Pol I) is tightly coordinated with cell growth. Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability. Inhibition of mTOR signaling by rapamycin inactivates TIF-IA and impairs transcription-initiation complex formation. Moreover, rapamycin treatment leads to translocation of TIF-IA into the cytoplasm. Rapamycin-mediated inactivation of TIF-IA is caused by hypophosphorylation of Se 44 (S44) and hyperphosphorylation of Se 199 (S199). Phosphorylation at these sites affects TIF-IA activity in opposite ways, for example, phosphorylation of S44 activates and S199 inactivates TIF-IA. The results identify a new target formTOR-signaling pathways and elucidate the molecular mechanism underlying mTOR-dependent regulation of RNA synthesis.

  5. mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability

    PubMed Central

    Mayer, Christine; Zhao, Jian; Yuan, Xuejun; Grummt, Ingrid

    2004-01-01

    In cycling cells, transcription of ribosomal RNA genes by RNA polymerase I (Pol I) is tightly coordinated with cell growth. Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability. Inhibition of mTOR signaling by rapamycin inactivates TIF-IA and impairs transcription-initiation complex formation. Moreover, rapamycin treatment leads to translocation of TIF-IA into the cytoplasm. Rapamycin-mediated inactivation of TIF-IA is caused by hypophosphorylation of Ser 44 (S44) and hyperphosphorylation of Ser 199 (S199). Phosphorylation at these sites affects TIF-IA activity in opposite ways, for example, phosphorylation of S44 activates and S199 inactivates TIF-IA. The results identify a new target for mTOR-signaling pathways and elucidate the molecular mechanism underlying mTOR-dependent regulation of rRNA synthesis. PMID:15004009

  6. 32 CFR 199.18 - Uniform HMO Benefit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... schedule, including frequency or age specifications for: (i) Laboratory and x-ray tests, including blood lead, rubella, cholesterol, fecal occult blood testing, and mammography; (ii) Pap smears; (iii) Eye exams; (iv) Immunizations; (v) Periodic health promotion and disease prevention exams; (vi) Blood...

  7. 32 CFR 199.18 - Uniform HMO Benefit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... schedule, including frequency or age specifications for: (i) Laboratory and x-ray tests, including blood lead, rubella, cholesterol, fecal occult blood testing, and mammography; (ii) Pap smears; (iii) Eye exams; (iv) Immunizations; (v) Periodic health promotion and disease prevention exams; (vi) Blood...

  8. 32 CFR 199.18 - Uniform HMO Benefit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... schedule, including frequency or age specifications for: (i) Laboratory and x-ray tests, including blood lead, rubella, cholesterol, fecal occult blood testing, and mammography; (ii) Pap smears; (iii) Eye exams; (iv) Immunizations; (v) Periodic health promotion and disease prevention exams; (vi) Blood...

  9. Parental Hostility as a Predictor of Parental Authority and Adolescent Self-Esteem.

    ERIC Educational Resources Information Center

    Buri, John R.; And Others

    Research shows that hostility may lead to deleterious consequences for health, anger, aggressive behavior, and interpersonal relationships. This study investigated the relation of parents' hostility levels to both the self-esteem (SE) of college-aged participants and the adolescents' phenomenological assessments of parental authority. The 199…

  10. 46 CFR 199.630 - Alternatives for passenger vessels in a specified service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Applicable Not Applicable. 199.211(a): Quantity of lifebuoys No Alternative 199.630(k) 199.630(k) 199.630(k) 199.630(k). Notes: 1 Alternative applies if the vessel operates on a route no more than 50 nautical..., vessels may carry at least 12 hand red flare distress signals approved under approval series 160.021 or...

  11. 46 CFR 199.630 - Alternatives for passenger vessels in a specified service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Applicable Not Applicable. 199.211(a): Quantity of lifebuoys No Alternative 199.630(k) 199.630(k) 199.630(k) 199.630(k). Notes: 1 Alternative applies if the vessel operates on a route no more than 50 nautical..., vessels may carry at least 12 hand red flare distress signals approved under approval series 160.021 or...

  12. Ratiometric Imaging Using a Single Dye Enables Simultaneous Visualization of Rac1 and Cdc42 Activation.

    PubMed

    MacNevin, Christopher J; Toutchkine, Alexei; Marston, Daniel J; Hsu, Chia-Wen; Tsygankov, Denis; Li, Li; Liu, Bei; Qi, Timothy; Nguyen, Dan-Vinh; Hahn, Klaus M

    2016-03-02

    Biosensors that report endogenous protein activity in vivo can be based on environment-sensing fluorescent dyes. The dyes can be attached to reagents that bind selectively to a specific conformation of the targeted protein, such that binding leads to a fluorescence change. Dyes that are sufficiently bright for use at low, nonperturbing intracellular concentrations typically undergo changes in intensity rather than the shifts in excitation or emission maxima that would enable precise quantitation through ratiometric imaging. We report here mero199, an environment-sensing dye that undergoes a 33 nm solvent-dependent shift in excitation. The dye was used to generate a ratiometric biosensor of Cdc42 (CRIB199) without the need for additional fluorophores. CRIB199 was used in the same cell with a FRET sensor of Rac1 activation to simultaneously observe Cdc42 and Rac1 activity in cellular protrusions, indicating that Rac1 but not Cdc42 activity was reduced during tail retraction, and specific protrusions had reduced Cdc42 activity. A novel program (EdgeProps) used to correlate localized activation with cell edge dynamics indicated that Rac1 was specifically reduced during retraction.

  13. Childhood lead poisoning from the smelter in Torreón, México.

    PubMed

    Soto-Jiménez, Martin F; Flegal, Arthur R

    2011-05-01

    Lead concentrations and isotopic compositions in blood samples of 34 children (ages 2-17 years) living within a 113 km(2) area of a silver-zinc-lead smelter plant in Torreón, México were compared to those of associated environmental samples (soil, aerosols, and outdoor and indoor dust) to identify the principal source(s) of environmental and human lead contamination in the area. Lead concentrations of soil and outdoor dust ranged 130-12,050 and 150-14,365 μg g(-1), respectively. Concentrations were greatest near the smelter, with the highest levels corresponding with the prevailing wind direction, and orders of magnitude above background concentrations of 7.3-33.3 μg g(-1). Atmospheric lead depositions in the city varied between 130 and 1350 μg m(-2) d(-1), again with highest rates <1 km from the smelter. Blood lead (PbB) concentrations (11.0±5.3 μg dl(-1)) levels in the children ranged 5.0-25.8 μg dl(-1), which is 3-14 times higher than the current average (1.9 μg dl(-1)) of children (ages 1-5 years) in the US. Lead isotopic ratios ((206)Pb/(207)Pb, (208)Pb/(207)Pb) of the urban dust and soil (1.200±0.009, 2.467±0.003), aerosols (1.200±0.002, 2.466±0.002), and PbB (1.199±0.001, 2.468±0.002) were indistinguishable from each other, as well as those of the lead ores processed at the smelter (1.199±0.007, 2.473±0.007). Consequently, an elevated PbB concentrations of the children in Torreón, as well as in their environment, are still dominated by industrial emissions from the smelter located within the city, in spite of new controls on atmospheric releases from the facility. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. 46 CFR 199.250 - Drills.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Drills. 199.250 Section 199.250 Shipping COAST GUARD... CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.250 Drills. (a) An abandon-ship drill and a fire drill, as described in § 199.180, must be conducted on each passenger vessel at...

  15. 46 CFR 199.250 - Drills.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Drills. 199.250 Section 199.250 Shipping COAST GUARD... CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.250 Drills. (a) An abandon-ship drill and a fire drill, as described in § 199.180, must be conducted on each passenger vessel at...

  16. 46 CFR 199.250 - Drills.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Drills. 199.250 Section 199.250 Shipping COAST GUARD... CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.250 Drills. (a) An abandon-ship drill and a fire drill, as described in § 199.180, must be conducted on each passenger vessel at...

  17. 46 CFR 199.250 - Drills.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Drills. 199.250 Section 199.250 Shipping COAST GUARD... CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.250 Drills. (a) An abandon-ship drill and a fire drill, as described in § 199.180, must be conducted on each passenger vessel at...

  18. 46 CFR 199.250 - Drills.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Drills. 199.250 Section 199.250 Shipping COAST GUARD... CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.250 Drills. (a) An abandon-ship drill and a fire drill, as described in § 199.180, must be conducted on each passenger vessel at...

  19. 46 CFR 199.202 - Rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Rescue boats. 199.202 Section 199.202 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.202 Rescue boats... least one rescue boat approved under approval series 160.156 that is equipped as specified in table 199...

  20. 46 CFR 199.202 - Rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boats. 199.202 Section 199.202 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.202 Rescue boats... least one rescue boat approved under approval series 160.156 that is equipped as specified in table 199...

  1. 46 CFR 199.202 - Rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Rescue boats. 199.202 Section 199.202 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.202 Rescue boats... least one rescue boat approved under approval series 160.156 that is equipped as specified in table 199...

  2. 46 CFR 199.202 - Rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Rescue boats. 199.202 Section 199.202 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.202 Rescue boats... least one rescue boat approved under approval series 160.156 that is equipped as specified in table 199...

  3. 46 CFR 199.202 - Rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Rescue boats. 199.202 Section 199.202 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.202 Rescue boats... least one rescue boat approved under approval series 160.156 that is equipped as specified in table 199...

  4. Monitoring of peri-distal gastrectomy carbohydrate antigen 19-9 level in gastric juice and its significance

    PubMed Central

    Xu, A-Man; Huang, Lei; Han, Wen-Xiu; Wei, Zhi-Jian

    2014-01-01

    Gastric carcinoma is one of the most common and deadly malignancies nowadays, and carbohydrate antigen 19-9 (CA 19-9) in gastric juice has been rarely studied. To compare peri-distal gastrectomy (DG) gastric juice and serum CA 19-9 and reveal its significance, we selected 67 patients diagnosed with gastric carcinoma who underwent DG, and collected their perioperative gastric juice whose CA 19-9 was detected, with serum CA 19-9 monitored as a comparison. We found that: gastric juice CA 19-9 pre-gastrectomy was significantly correlated with tumor TNM classification, regarding tumor size, level of gastric wall invaded, differentiated grade and number of metastatic lymph nodes as influencing factors, while serum CA 19-9 revealed little information; gastric juice CA 19-9 was significantly correlated with radical degree, and regarded number of resected lymph nodes and classification of cutting edge as impact factors; thirteen patients whose gastric juice CA 19-9 rose post-DG showed features indicating poor prognosis; the difference of gastric juice CA 19-9 between pre- and post-gastrectomy was correlated with tumor TNM classification and radical degree, and regarded tumor size, number of resected metastatic and normal lymph nodes, sum of distances from tumor to cutting edges and classification of cutting edge as influential factors. We conclude that peri-DG gastric juice CA 19-9 reveals much information about tumor and radical gastrectomy, and may indicate prognosis; while serum CA 19-9 has limited significance. PMID:24482710

  5. Interfering Effect of Black Tea Consumption on Diagnosis of Pancreatic Cancer by CA 19-9.

    PubMed

    Al-Janabi, Ali Abdul Hussein S; Tawfeeq, Ekhlas F

    2017-06-01

    The study aims to determine the possible effects of black tea consumption on the level of CA 19-9 antigen in the human body. The level of CA 19-9 was measured in 270 healthy individuals who consumed heavy amounts of black tea. About 43.3 % of involved individuals were revealed to have elevated levels of CA 19-9. Males with high values of CA 19-9 represented the greatest number of involved individuals. The cutoff value of high levels of CA 19-9 in all individuals was ranged 69-105 U/ml. Consuming heavy amounts of black tea could be considered an important interfering factor that affects the levels of CA 19-9. The cutoff or predictive value of CA 19-9 in heavy-consuming people of black tea was determined.

  6. MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1.

    PubMed

    Li, Qiang; Xia, Xuefeng; Ji, Jie; Ma, Jianghui; Tao, Liang; Mo, Linjun; Chen, Wei

    2017-05-16

    Several studies have reported reduced miRNA-199a-3p (miR-199a-3p) in different human malignancies, however, little is known about miR-199a-3p in cholangiocarcinoma cells. In this study, we demonstrate the essential role and mechanism of miR-199a-3p in regulating cisplatin sensitivity in cholangiocarcinoma cell lines. Using a CCK-8 cell counting assay we found that expression of miR-199a-3p was positively correlated with cisplatin sensitivity in cholangiocarcinoma cell lines. MiR-199a-3p overexpression could decrease the proliferation rate and increase apoptosis of cholangiocarcinoma cells in the presence of cisplatin, while miR-199a-3p inhibition had the opposite effect. Further study demonstrated that mTOR was the target gene of miR-199a-3p, and that miR-199a-3p mimics could inhibit expression of mTOR, which consequently reduced the phosphorylation of its downstream proteins 4EBP1 and p70s6k. Rescue experiments proved that miR-199a-3p could increase the cisplatin sensitivity of cholangiocarcinoma cell lines by regulating mTOR expression. Moreover, we also found that miR-199a-3p overexpression could reduce cisplatin induced MDR1 expression by decreasing the synthesis and increasing the degradation of MDR1, thus enhancing the effectiveness of cisplatin in cholangiocarcinoma. In conclusion, miR-199a-3p could increase cisplatin sensitivity of cholangiocarcinoma cell lines by inhibiting the activity of the mTOR signaling pathway and decreasing the expression of MDR1.

  7. Periostin and CA242 as potential diagnostic serum biomarkers complementing CA19.9 in detecting pancreatic cancer.

    PubMed

    Dong, Dong; Jia, Li; Zhang, Lufang; Ma, Na; Zhang, Aimin; Zhou, Yunli; Ren, Li

    2018-06-26

    Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with few biomarkers to guide treatment options. Carbohydrate antigen 19.9 (CA19.9), the mainly used biomarker for PDAC, is not sensitive and specific enough for the detection of the disease. This study was aimed to evaluate serum periostin (POSTN) and CA242 as potential diagnostic biomarkers complementing CA19.9 in detecting pancreatic cancer. Blood samples were from 362 participants, including 213 patients with different stages of PDAC, 75 patients with benign pancreatic disease and 74 healthy individuals. All samples were randomly divided into training set and validation set. CA19.9, CA242, POSTN, as well as carcinoembryonic antigen (CEA), were measured by ELISA or automated immunoassay. The receiver operating curve (ROC) analysis revealed that the performances of CA19.9 in the validation group were improved by the marker panel composed of CA19.9, POSTN and CA242, to discriminate early-stage PDAC not only from healthy controls (AUC CA 19.9 = 0.94 vs. AUC CA 19.9 + POSTN + CA 242 = 0.98, P < 0.05) but also from benign conditions (AUC CA 19.9 = 0.87 vs. AUC CA 19.9 + POSTN + CA 242 = 0.90, P < 0.05). In addition, POSTN retained significant diagnostic capabilities to distinguish PDAC CA19.9-negative from healthy controls (AUC POSTN = 0.87) as well as from benign conditions (AUC POSTN = 0.84) in the whole set. This study suggested that POSTN and CA242 are potential diagnostic serum biomarkers complementing CA19.9 in detecting early pancreatic cancer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. 49 CFR 37.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 37.199 Section 37.199 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.199 [Reserved] ...

  9. 7 CFR 4279.188-4279.199 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false [Reserved] 4279.188-4279.199 Section 4279.188-4279.199 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE... Loans §§ 4279.188-4279.199 [Reserved] ...

  10. 7 CFR 4279.188-4279.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false [Reserved] 4279.188-4279.199 Section 4279.188-4279.199 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE... Loans §§ 4279.188-4279.199 [Reserved] ...

  11. 7 CFR 4279.188-4279.199 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false [Reserved] 4279.188-4279.199 Section 4279.188-4279.199 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE... Loans §§ 4279.188-4279.199 [Reserved] ...

  12. 7 CFR 4279.188-4279.199 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false [Reserved] 4279.188-4279.199 Section 4279.188-4279.199 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE... Loans §§ 4279.188-4279.199 [Reserved] ...

  13. 7 CFR 4279.188-4279.199 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false [Reserved] 4279.188-4279.199 Section 4279.188-4279.199 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE... Loans §§ 4279.188-4279.199 [Reserved] ...

  14. High-efficiency and low-background multi-segmented proportional gas counter for β-decay spectroscopy

    NASA Astrophysics Data System (ADS)

    Mukai, M.; Hirayama, Y.; Watanabe, Y. X.; Schury, P.; Jung, H. S.; Ahmed, M.; Haba, H.; Ishiyama, H.; Jeong, S. C.; Kakiguchi, Y.; Kimura, S.; Moon, J. Y.; Oyaizu, M.; Ozawa, A.; Park, J. H.; Ueno, H.; Wada, M.; Miyatake, H.

    2018-03-01

    A multi-segmented proportional gas counter (MSPGC) with high detection efficiency and low-background event rate has been developed for β-decay spectroscopy. The MSPGC consists of two cylindrically aligned layers of 16 counters (32 counters in total). Each counter has a long active length and small trapezoidal cross-section, and the total solid angle of the 32 counters is 80% of 4 π. β-rays are distinguished from the background events including cosmic-rays by analyzing the hit patterns of independent counters. The deduced intrinsic detection efficiency of each counter was almost 100%. The measured background event rate was 0.11 counts per second using the combination of veto counters for cosmic-rays and lead block shields for background γ-rays. The MSPGC was applied to measure the β-decay half-lives of 198Ir and 199mPt. The evaluated half-lives of T1/2 = 9 . 8(7) s and 12.4(7) s for 198Ir and 199mPt, respectively, were in agreement with previously reported values. The estimated absolute detection efficiency of the MSPGC from GEANT4 simulations was consistent with the evaluated efficiency from the analysis of the β- γ spectroscopy of 199Pt, saturating at approximately 60% for Qβ > 4 MeV.

  15. Correlation between some parameters of lead absorption and lead intoxication

    PubMed Central

    Waldron, H. A.

    1971-01-01

    Waldron, H. A. (1971).Brit. J. industr. Med.,28, 195-199. Correlation between some parameters of lead absorption and lead intoxication. Use has been made of data collected over a number of years from workers exposed to a lead hazard in a motor-car factory. The correlations between various parameters of lead absorption and lead intoxication were computed, including blood and urine lead concentrations, urinary coproporphyrin, ALA and PBG concentrations, and haemoglobin concentration. In all, 15 correlation coefficients were calculated, of which only six showed a statistically significant result (i.e., P<0·05). These six were blood lead and urine lead (r = 0·38, P<0·001), urine lead and coproporphyrin (r = 0·42, P<0·001), urine lead and ALA (r = 0·43, P<0·001), coproporphyrin and ALA (r = 0·75, P<0·001), ALA and PBG (r = 0·49, P<0·001), and urine lead and PBG (r = 0·19, P<0·05). PMID:5572689

  16. 7 CFR 25.105-25.199 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false [Reserved] 25.105-25.199 Section 25.105-25.199 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Area Requirements §§ 25.105-25.199 [Reserved] ...

  17. 7 CFR 25.105-25.199 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false [Reserved] 25.105-25.199 Section 25.105-25.199 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Area Requirements §§ 25.105-25.199 [Reserved] ...

  18. 7 CFR 25.105-25.199 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false [Reserved] 25.105-25.199 Section 25.105-25.199 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Area Requirements §§ 25.105-25.199 [Reserved] ...

  19. 7 CFR 25.105-25.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false [Reserved] 25.105-25.199 Section 25.105-25.199 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Area Requirements §§ 25.105-25.199 [Reserved] ...

  20. 7 CFR 25.105-25.199 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false [Reserved] 25.105-25.199 Section 25.105-25.199 Agriculture Office of the Secretary of Agriculture RURAL EMPOWERMENT ZONES AND ENTERPRISE COMMUNITIES Area Requirements §§ 25.105-25.199 [Reserved] ...

  1. CA19-9 serum levels predict micrometastases in patients with gastric cancer

    PubMed Central

    Potrc, Stojan; Mis, Katarina; Plankl, Mojca; Mars, Tomaz

    2016-01-01

    Abstract Background We explored the prognostic value of the up-regulated carbohydrate antigen (CA19-9) in node-negative patients with gastric cancer as a surrogate marker for micrometastases. Patients and methods Micrometastases were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for a subgroup of 30 node-negative patients. This group was used to determine the cut-off for preoperative CA19-9 serum levels as a surrogate marker for micrometastases. Then 187 node-negative T1 to T4 patients were selected to validate the predictive value of this CA19-9 threshold. Results Patients with micrometastases had significantly higher preoperative CA19-9 serum levels compared to patients without micrometastases (p = 0.046). CA19-9 serum levels were significantly correlated with tumour site, tumour diameter, and perineural invasion. Although not reaching significance, subgroup analysis showed better five-year survival rates for patients with CA19-9 serum levels below the threshold, compared to patients with CA19-9 serum levels above the cut-off. The cumulative survival for T2 to T4 node-negative patients was significantly better with CA19-9 serum levels below the cut-off (p = 0.04). Conclusions Preoperative CA19-9 serum levels can be used to predict higher risk for haematogenous spread and micrometastases in node-negative patients. However, CA19-9 serum levels lack the necessary sensitivity and specificity to reliably predict micrometastases. PMID:27247553

  2. 46 CFR 199.60 - Communications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Communications. 199.60 Section 199.60 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.60 Communications. (a) Radio...) Onboard communications and alarm systems. Each vessel must meet the requirements for onboard...

  3. 46 CFR 199.20 - Exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Exemptions. 199.20 Section 199.20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS General § 199.20 Exemptions. (a) Vessels engaged on international voyages. (1...

  4. 49 CFR 199.215 - Alcohol concentration.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Alcohol concentration. 199.215 Section 199.215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.215 Alcohol concentration. Each operator shall prohibit a covered employee from...

  5. 49 CFR 199.215 - Alcohol concentration.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Alcohol concentration. 199.215 Section 199.215... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.215 Alcohol concentration. Each operator shall prohibit a covered employee from...

  6. 46 CFR 199.60 - Communications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Communications. 199.60 Section 199.60 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.60 Communications. (a) Radio...) Onboard communications and alarm systems. Each vessel must meet the requirements for onboard...

  7. 46 CFR 199.90 - Operating instructions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Operating instructions. 199.90 Section 199.90 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.90 Operating instructions...

  8. 46 CFR 199.60 - Communications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Communications. 199.60 Section 199.60 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.60 Communications. (a) Radio...) Onboard communications and alarm systems. Each vessel must meet the requirements for onboard...

  9. Identification of bile survivin and carbohydrate antigen 199 in distinguishing cholangiocarcinoma from benign obstructive jaundice.

    PubMed

    Liu, Yanfeng; Sun, Jingxian; Zhang, Qiangbo; Jin, Bin; Zhu, Min; Zhang, Zongli

    2017-01-01

    To investigate whether bile survivin and carbohydrate antigen 199 (CA199) can be helpful in distinguishing cholangiocarcinoma (malignant obstructive jaundice) from benign obstructive jaundice. Receiver operating characteristic curve was used to evaluate the feasibility of bile survivin and CA199 in differentiating cholangiocarcinoma from benign obstructive jaundice. The area under the curve for survivin and CA199 in bile and serum were 0.780 (p < 0.001), 0.6 (p = 0.084), 0.746 (p < 0.001) and 0.542 (p = 0.464), respectively. Combination of bile survivin and CA199 could improve the diagnostic capability. Bile survivin and CA199 are significantly increased in patients with cholangiocarcinoma and may be useful biomarkers in differentiating distinguishing cholangiocarcinoma from benign obstructive jaundice.

  10. Ionizing Radiation Deregulates the MicroRNA Expression Profile in Differentiated Thyroid Cells.

    PubMed

    Penha, Ricardo Cortez Cardoso; Pellecchia, Simona; Pacelli, Roberto; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo

    2018-03-01

    Ionizing radiation (IR) is a well-known risk factor for papillary thyroid cancer, and it has been reported to deregulate microRNA expression, which is important to thyroid carcinogenesis. Therefore, this study investigated the impact of IR on microRNA expression profile of the normal thyroid cell line (FRTL-5 CL2), as well as its effect on radiosensitivity of thyroid cancer cell lines, especially the human anaplastic thyroid carcinoma cell line (8505c). The global microRNA expression profile of irradiated FRTL-5 CL2 cells (5 Gy X-ray) was characterized, and data were confirmed by quantitative real-time polymerase chain reaction evaluating the expression of rno-miR-10b-5p, rno-miR-33-5p, rno-miR-128-1-5p, rno-miR-199a-3p, rno-miR-296-5p, rno-miR-328a-3p, and rno-miR-541-5p in irradiated cells. The miR-199a-3p and miR-10b-5p targets were validated by quantitative real-time polymerase chain reaction, Western blot, and luciferase target assays. The effects of miR-199a-3p and miR-10b-5p on DNA repair were determined by evaluating the activation of the protein kinases ataxia-telangiectasia mutated, ataxia telangiectasia, and Rad3-related and the serine 39 phosphorylation of variant histone H2AX as an indirect measure of double-strand DNA breaks in irradiated FRTL-5 CL2 cells. The impact of miR-10b-5p on radiosensitivity was analyzed by cell counting and MTT assays in FRTL-5 CL2, Kras-transformed FRTL-5 CL2 (FRTL KiKi), and 8505c cell lines. The results reveal that miR-10b-5p and miR-199a-3p display the most pronounced alterations in expression in irradiated FRTL-5 CL2 cells. Dicer1 and Lin28b were validated as targets of miR-10b-5p and miR-199a-3p, respectively. Functional studies demonstrate that miR-10b-5p increases the growth rate of FRTL-5 CL2 cells, while miR-199a-3p inhibits their proliferation. Moreover, both of these microRNAs negatively affect homologous recombination repair, reducing activated ataxia-telangiectasia mutated and Rad3-related protein levels, consequently leading to an accumulation of the serine 39 phosphorylation of variant histone H2AX. Interestingly, the overexpression of miR-10b-5p decreases the viability of the irradiated FRTL5-CL2 and 8505c cell lines. Consistent with this observation, its inhibition in FRTL KiKi cells, which display high basal expression levels of miR-10b-5p, leads to the opposite effect. These results demonstrate that IR deregulates microRNA expression, affecting the double-strand DNA breaks repair efficiency of irradiated thyroid cells, and suggest that miR-10b-5p overexpression may be an innovative approach for anaplastic thyroid cancer therapy by increasing cancer cell radiosensitivity.

  11. 46 CFR 199.07 - Additional equipment and requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Additional equipment and requirements. 199.07 Section 199.07 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS General § 199.07 Additional equipment and...

  12. 12 CFR 303.188-303.199 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false [Reserved] 303.188-303.199 Section 303.188-303.199 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE FILING PROCEDURES International Banking §§ 303.188-303.199 [Reserved] ...

  13. 12 CFR 303.188-303.199 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false [Reserved] 303.188-303.199 Section 303.188-303.199 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE FILING PROCEDURES International Banking §§ 303.188-303.199 [Reserved] ...

  14. 12 CFR 303.188-303.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false [Reserved] 303.188-303.199 Section 303.188-303.199 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE FILING PROCEDURES International Banking §§ 303.188-303.199 [Reserved] ...

  15. 12 CFR 303.188-303.199 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false [Reserved] 303.188-303.199 Section 303.188-303.199 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE FILING PROCEDURES International Banking §§ 303.188-303.199 [Reserved] ...

  16. 12 CFR 303.188-303.199 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false [Reserved] 303.188-303.199 Section 303.188-303.199 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION PROCEDURE AND RULES OF PRACTICE FILING PROCEDURES International Banking §§ 303.188-303.199 [Reserved] ...

  17. 46 CFR 199.510 - EPIRB requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false EPIRB requirements. 199.510 Section 199.510 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS... § 199.510 EPIRB requirements. (a) Each vessel must carry a category 1 406 MHz satellite EPIRB meeting...

  18. 46 CFR 199.510 - EPIRB requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false EPIRB requirements. 199.510 Section 199.510 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS... § 199.510 EPIRB requirements. (a) Each vessel must carry a category 1 406 MHz satellite EPIRB meeting...

  19. 46 CFR 199.03 - Relationship to international standards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Relationship to international standards. 199.03 Section 199.03 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS General § 199.03 Relationship to international...

  20. 40 CFR 272.152-272.199 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 27 2011-07-01 2011-07-01 false [Reserved] 272.152-272.199 Section 272.152-272.199 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona §§ 272.152-272.199 [Reserved] ...

  1. 40 CFR 272.152-272.199 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 28 2012-07-01 2012-07-01 false [Reserved] 272.152-272.199 Section 272.152-272.199 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona §§ 272.152-272.199 [Reserved] ...

  2. 40 CFR 272.152-272.199 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false [Reserved] 272.152-272.199 Section 272.152-272.199 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona §§ 272.152-272.199 [Reserved] ...

  3. 40 CFR 272.152-272.199 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false [Reserved] 272.152-272.199 Section 272.152-272.199 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona §§ 272.152-272.199 [Reserved] ...

  4. 40 CFR 272.152-272.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false [Reserved] 272.152-272.199 Section 272.152-272.199 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) APPROVED STATE HAZARDOUS WASTE MANAGEMENT PROGRAMS Arizona §§ 272.152-272.199 [Reserved] ...

  5. 14 CFR 21.199 - Issue of special flight permits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Issue of special flight permits. 21.199 Section 21.199 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS Airworthiness Certificates § 21.199 Issue of...

  6. 49 CFR 199.243 - Referral, evaluation, and treatment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.243 Referral, evaluation, and treatment. (a) Each... abuse professionals and counseling and treatment programs. (b) Each covered employee who engages in conduct prohibited under §§ 199.215 through 199.223 shall be evaluated by a substance abuse professional...

  7. 49 CFR 199.243 - Referral, evaluation, and treatment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.243 Referral, evaluation, and treatment. (a) Each... abuse professionals and counseling and treatment programs. (b) Each covered employee who engages in conduct prohibited under §§ 199.215 through 199.223 shall be evaluated by a substance abuse professional...

  8. 49 CFR 199.243 - Referral, evaluation, and treatment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.243 Referral, evaluation, and treatment. (a) Each... abuse professionals and counseling and treatment programs. (b) Each covered employee who engages in conduct prohibited under §§ 199.215 through 199.223 shall be evaluated by a substance abuse professional...

  9. 49 CFR 199.243 - Referral, evaluation, and treatment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.243 Referral, evaluation, and treatment. (a) Each... abuse professionals and counseling and treatment programs. (b) Each covered employee who engages in conduct prohibited under §§ 199.215 through 199.223 shall be evaluated by a substance abuse professional...

  10. 49 CFR 199.243 - Referral, evaluation, and treatment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.243 Referral, evaluation, and treatment. (a) Each... abuse professionals and counseling and treatment programs. (b) Each covered employee who engages in conduct prohibited under §§ 199.215 through 199.223 shall be evaluated by a substance abuse professional...

  11. 49 CFR 199.202 - Alcohol misuse plan.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Alcohol misuse plan. 199.202 Section 199.202... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.202 Alcohol misuse plan. Each operator must maintain and follow a written alcohol...

  12. 49 CFR 199.202 - Alcohol misuse plan.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Alcohol misuse plan. 199.202 Section 199.202... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.202 Alcohol misuse plan. Each operator must maintain and follow a written alcohol...

  13. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator shall...

  14. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator shall...

  15. 46 CFR 108.199 - Arrangement of sleeping spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Arrangement of sleeping spaces. 108.199 Section 108.199... AND EQUIPMENT Construction and Arrangement Accommodation Spaces § 108.199 Arrangement of sleeping spaces. To the extent practicable, each occupation group must be berthed together in sleeping spaces...

  16. 46 CFR 108.199 - Arrangement of sleeping spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Arrangement of sleeping spaces. 108.199 Section 108.199... AND EQUIPMENT Construction and Arrangement Accommodation Spaces § 108.199 Arrangement of sleeping spaces. To the extent practicable, each occupation group must be berthed together in sleeping spaces...

  17. 46 CFR 108.199 - Arrangement of sleeping spaces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Arrangement of sleeping spaces. 108.199 Section 108.199... AND EQUIPMENT Construction and Arrangement Accommodation Spaces § 108.199 Arrangement of sleeping spaces. To the extent practicable, each occupation group must be berthed together in sleeping spaces...

  18. 46 CFR 108.199 - Arrangement of sleeping spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Arrangement of sleeping spaces. 108.199 Section 108.199... AND EQUIPMENT Construction and Arrangement Accommodation Spaces § 108.199 Arrangement of sleeping spaces. To the extent practicable, each occupation group must be berthed together in sleeping spaces...

  19. 46 CFR 108.199 - Arrangement of sleeping spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Arrangement of sleeping spaces. 108.199 Section 108.199... AND EQUIPMENT Construction and Arrangement Accommodation Spaces § 108.199 Arrangement of sleeping spaces. To the extent practicable, each occupation group must be berthed together in sleeping spaces...

  20. 49 CFR 199.245 - Contractor employees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Contractor employees. 199.245 Section 199.245... Prevention Program § 199.245 Contractor employees. (a) With respect to those covered employees who are contractors or employed by a contractor, an operator may provide by contract that the alcohol testing...

  1. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

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

    Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

  2. The miR-199-dynamin regulatory axis controls receptor-mediated endocytosis.

    PubMed

    Aranda, Juan F; Canfrán-Duque, Alberto; Goedeke, Leigh; Suárez, Yajaira; Fernández-Hernando, Carlos

    2015-09-01

    Small non-coding RNAs (microRNAs) are important regulators of gene expression that modulate many physiological processes; however, their role in regulating intracellular transport remains largely unknown. Intriguingly, we found that the dynamin (DNM) genes, a GTPase family of proteins responsible for endocytosis in eukaryotic cells, encode the conserved miR-199a and miR-199b family of miRNAs within their intronic sequences. Here, we demonstrate that miR-199a and miR-199b regulate endocytic transport by controlling the expression of important mediators of endocytosis such as clathrin heavy chain (CLTC), Rab5A, low-density lipoprotein receptor (LDLR) and caveolin-1 (Cav-1). Importantly, miR-199a-5p and miR-199b-5p overexpression markedly inhibits CLTC, Rab5A, LDLR and Cav-1 expression, thus preventing receptor-mediated endocytosis in human cell lines (Huh7 and HeLa). Of note, miR-199a-5p inhibition increases target gene expression and receptor-mediated endocytosis. Taken together, our work identifies a new mechanism by which microRNAs regulate intracellular trafficking. In particular, we demonstrate that the DNM, miR-199a-5p and miR-199b-5p genes act as a bifunctional locus that regulates endocytosis, thus adding an unexpected layer of complexity in the regulation of intracellular trafficking. © 2015. Published by The Company of Biologists Ltd.

  3. [Usefulness of preoperative assay CEA and CA 19-9 in colorectal cancer patients].

    PubMed

    Grotowski, M; Maruszyński, M; Piechota, W

    2001-12-01

    Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known tumor markers expressed by colorectal cancer (CRC), particularly in advanced cases. In this study serological expression of CEA and CA19-9 concerning different clinicopathological factors and sensitivity of diagnosis of CRC by combination of both markers were evaluated. Eighty one patients with diagnosed CRC were in this study included. According to Dukes' classification there were 11 in stage A, 34 in stage B, 17 in stage C and 19 in stage D. Blood samples were collected before operation. CEA and CA19-9 were determined by MEIA (normal range 0-3 ng/ml for CEA and 0-37 U/ml for CA19-9). The statistical analysis revealed that the CEA well correlated with histological type, liver metastasis and term of symptoms. The CA19-9 well correlated with liver metastasis, peritoneal dissemination, nodal involvement and cancer localization. The levels of CEA and CA19-9 increased with stage of the tumor, but only in stage D the difference was statistically significant (for CEA p = 0.005, for CA19-9 p = 0.039). At time of diagnosis 50.6% of the patients had elevated serum levels of CEA and 29.6% of CA19-9. In combination of both antigens this elevation was in 54.3% of CRC patients. The common use of CEA and CA19-9 was more efficacious in identification of patients at high risk. The combination assay of CEA and CA19-9 did not cause a significant increase of sensitivity in diagnosis CRC.

  4. 10 CFR 205.199I - Remedies.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Remedies. 205.199I Section 205.199I Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.199I Remedies. (a) A Remedial Order, a... third persons for administrative expenses of effectuating appropriate remedies, and to take such other...

  5. 10 CFR 205.199I - Remedies.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Remedies. 205.199I Section 205.199I Energy DEPARTMENT OF... of Proposed Disallowance, and Order of Disallowance § 205.199I Remedies. (a) A Remedial Order, a... third persons for administrative expenses of effectuating appropriate remedies, and to take such other...

  6. 49 CFR 199.107 - Drug testing laboratory.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Drug testing laboratory. 199.107 Section 199.107... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.107 Drug testing laboratory. (a) Each operator shall use for the drug testing required by this...

  7. 49 CFR 199.101 - Anti-drug plan.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Anti-drug plan. 199.101 Section 199.101... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.101 Anti-drug plan. (a) Each operator shall maintain and follow a written anti-drug plan that...

  8. 49 CFR 199.101 - Anti-drug plan.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Anti-drug plan. 199.101 Section 199.101... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.101 Anti-drug plan. (a) Each operator shall maintain and follow a written anti-drug plan that...

  9. 49 CFR 199.107 - Drug testing laboratory.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Drug testing laboratory. 199.107 Section 199.107... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.107 Drug testing laboratory. (a) Each operator shall use for the drug testing required by this...

  10. 49 CFR 199.107 - Drug testing laboratory.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Drug testing laboratory. 199.107 Section 199.107... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.107 Drug testing laboratory. (a) Each operator shall use for the drug testing required by this...

  11. 49 CFR 199.101 - Anti-drug plan.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Anti-drug plan. 199.101 Section 199.101... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.101 Anti-drug plan. (a) Each operator shall maintain and follow a written anti-drug plan that...

  12. 46 CFR 199.261 - Survival craft.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft. 199.261 Section 199.261 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.261 Survival craft. (a) Each survival craft must be approved and equipped as follows: (1) Each lifeboat must be a totally...

  13. 32 CFR 199.13 - TRICARE Dental Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false TRICARE Dental Program. 199.13 Section 199.13...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.13 TRICARE Dental... delivery and administration of the TRICARE Dental Program (TDP) of the Uniformed Services of the Army, the...

  14. 32 CFR 199.13 - TRICARE Dental Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false TRICARE Dental Program. 199.13 Section 199.13...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.13 TRICARE Dental... delivery and administration of the TRICARE Dental Program (TDP) of the Uniformed Services of the Army, the...

  15. 32 CFR 199.13 - TRICARE Dental Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false TRICARE Dental Program. 199.13 Section 199.13...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.13 TRICARE Dental... delivery and administration of the TRICARE Dental Program (TDP) of the Uniformed Services of the Army, the...

  16. 37 CFR 1.99 - Third-party submission in published application.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... published application. 1.99 Section 1.99 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND... Provisions Information Disclosure Statement § 1.99 Third-party submission in published application. (a) A submission by a member of the public of patents or publications relevant to a pending published application...

  17. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Performance. 19.9 Section 19.9 Mineral... MINING PRODUCTS ELECTRIC CAP LAMPS § 19.9 Performance. In addition to the general design and the safety... respect to performance, as follows: (a) Time of burning and candlepower. Permissible electric cap lamps...

  18. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Performance. 19.9 Section 19.9 Mineral... MINING PRODUCTS ELECTRIC CAP LAMPS § 19.9 Performance. In addition to the general design and the safety... respect to performance, as follows: (a) Time of burning and candlepower. Permissible electric cap lamps...

  19. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Performance. 19.9 Section 19.9 Mineral... MINING PRODUCTS ELECTRIC CAP LAMPS § 19.9 Performance. In addition to the general design and the safety... respect to performance, as follows: (a) Time of burning and candlepower. Permissible electric cap lamps...

  20. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Performance. 19.9 Section 19.9 Mineral... MINING PRODUCTS ELECTRIC CAP LAMPS § 19.9 Performance. In addition to the general design and the safety... respect to performance, as follows: (a) Time of burning and candlepower. Permissible electric cap lamps...

  1. 49 CFR 199.101 - Anti-drug plan.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.101 Anti-drug plan. (b) The Associate Administrator or the State Agency that has submitted a... 49 Transportation 3 2013-10-01 2013-10-01 false Anti-drug plan. 199.101 Section 199.101...

  2. 49 CFR 199.107 - Drug testing laboratory.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Drug testing laboratory. 199.107 Section 199.107... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.107 Drug testing laboratory. (a) Each operator shall use for the drug testing required by this...

  3. 49 CFR 199.107 - Drug testing laboratory.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Drug testing laboratory. 199.107 Section 199.107... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.107 Drug testing laboratory. (a) Each operator shall use for the drug testing required by this...

  4. 49 CFR 572.199 - Pelvis iliac.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Pelvis iliac. 572.199 Section 572.199... Test Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso... the assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis...

  5. 49 CFR 572.199 - Pelvis iliac.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Pelvis iliac. 572.199 Section 572.199... Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso assembly... assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis accelerometer as...

  6. 49 CFR 572.199 - Pelvis iliac.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Pelvis iliac. 572.199 Section 572.199... Test Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso... the assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis...

  7. 49 CFR 572.199 - Pelvis iliac.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Pelvis iliac. 572.199 Section 572.199... Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso assembly... assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis accelerometer as...

  8. 49 CFR 572.199 - Pelvis iliac.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Pelvis iliac. 572.199 Section 572.199... Dummy, Small Adult Female § 572.199 Pelvis iliac. (a) The iliac is part of the lower torso assembly... assembled dummy (drawing 180-0000). The dummy is equipped with a laterally oriented pelvis accelerometer as...

  9. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  10. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  11. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  12. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  13. 46 CFR 199.262 - Rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Rescue boats. 199.262 Section 199.262 Shipping COAST... SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Cargo Vessels § 199.262 Rescue boats. (a) Each cargo vessel must carry at least one rescue boat. Each rescue boat must be approved under approval...

  14. 49 CFR 199.115 - Contractor employees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Contractor employees. 199.115 Section 199.115... § 199.115 Contractor employees. With respect to those employees who are contractors or employed by a contractor, an operator may provide by contract that the drug testing, education, and training required by...

  15. 46 CFR 199.100 - Manning of survival craft and supervision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Manning of survival craft and supervision. 199.100 Section 199.100 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.100 Manning of survival craft and supervision. (a...

  16. 26 CFR 1.199-3 - Domestic production gross receipts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Domestic production gross receipts. 1.199-3 Section 1.199-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Itemized Deductions for Individuals and Corporations (continued) § 1.199-3 Domestic production gross receipts. (a) In...

  17. 26 CFR 1.199-3 - Domestic production gross receipts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Domestic production gross receipts. 1.199-3 Section 1.199-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations (continued) § 1.199-3 Domestic production gross...

  18. 26 CFR 1.199-3 - Domestic production gross receipts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Domestic production gross receipts. 1.199-3 Section 1.199-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations (continued) § 1.199-3 Domestic production gross...

  19. 26 CFR 1.199-3 - Domestic production gross receipts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Domestic production gross receipts. 1.199-3 Section 1.199-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations (continued) § 1.199-3 Domestic production gross...

  20. 26 CFR 1.199-3 - Domestic production gross receipts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Domestic production gross receipts. 1.199-3 Section 1.199-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations (continued) § 1.199-3 Domestic production gross...

  1. 38 CFR 17.199 - Inspection of recognized State homes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... State homes. 17.199 Section 17.199 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Aid to States for Care of Veterans in State Homes § 17.199 Inspection of recognized State homes. Representatives of the Department of Veterans Affairs may inspect any State home at such times as...

  2. 38 CFR 17.199 - Inspection of recognized State homes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... State homes. 17.199 Section 17.199 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Aid to States for Care of Veterans in State Homes § 17.199 Inspection of recognized State homes. Representatives of the Department of Veterans Affairs may inspect any State home at such times as...

  3. 38 CFR 17.199 - Inspection of recognized State homes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... State homes. 17.199 Section 17.199 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Aid to States for Care of Veterans in State Homes § 17.199 Inspection of recognized State homes. Representatives of the Department of Veterans Affairs may inspect any State home at such times as...

  4. 38 CFR 17.199 - Inspection of recognized State homes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... State homes. 17.199 Section 17.199 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Aid to States for Care of Veterans in State Homes § 17.199 Inspection of recognized State homes. Representatives of the Department of Veterans Affairs may inspect any State home at such times as...

  5. 38 CFR 17.199 - Inspection of recognized State homes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... State homes. 17.199 Section 17.199 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Aid to States for Care of Veterans in State Homes § 17.199 Inspection of recognized State homes. Representatives of the Department of Veterans Affairs may inspect any State home at such times as...

  6. 49 CFR 199.221 - Use following an accident.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Use following an accident. 199.221 Section 199.221... Prevention Program § 199.221 Use following an accident. Each operator shall prohibit a covered employee who has actual knowledge of an accident in which his or her performance of covered functions has not been...

  7. 49 CFR 199.221 - Use following an accident.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Use following an accident. 199.221 Section 199.221... Prevention Program § 199.221 Use following an accident. Each operator shall prohibit a covered employee who has actual knowledge of an accident in which his or her performance of covered functions has not been...

  8. 46 CFR 199.640 - Alternatives for cargo vessels in a specified service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may comply with alternative requirements... Coastwise Great Lakes Lakes, bays, and sounds Rivers 199.60(c): Distress signals 199.640(b) 1 199.640(b) 1... capacity sufficient to accommodate the total number of people on board. The lifefloat launching arrangement...

  9. 46 CFR 199.640 - Alternatives for cargo vessels in a specified service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may comply with alternative requirements... Coastwise Great Lakes Lakes, bays, and sounds Rivers 199.60(c): Distress signals 199.640(b) 1 199.640(b) 1... capacity sufficient to accommodate the total number of people on board. The lifefloat launching arrangement...

  10. 46 CFR 199.640 - Alternatives for cargo vessels in a specified service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may comply with alternative requirements... Coastwise Great Lakes Lakes, bays, and sounds Rivers 199.60(c): Distress signals 199.640(b) 1 199.640(b) 1... capacity sufficient to accommodate the total number of people on board. The lifefloat launching arrangement...

  11. 46 CFR 199.640 - Alternatives for cargo vessels in a specified service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may comply with alternative requirements... Coastwise Great Lakes Lakes, bays, and sounds Rivers 199.60(c): Distress signals 199.640(b) 1 199.640(b) 1... capacity sufficient to accommodate the total number of people on board. The lifefloat launching arrangement...

  12. 46 CFR 199.640 - Alternatives for cargo vessels in a specified service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may comply with alternative requirements... Coastwise Great Lakes Lakes, bays, and sounds Rivers 199.60(c): Distress signals 199.640(b) 1 199.640(b) 1... capacity sufficient to accommodate the total number of people on board. The lifefloat launching arrangement...

  13. 49 CFR 199.219 - Pre-duty use.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Prevention Program § 199.219 Pre-duty use. Each operator shall prohibit a covered employee from using alcohol within four hours prior to performing covered functions, or, if an employee is called to duty to respond... 49 Transportation 3 2011-10-01 2011-10-01 false Pre-duty use. 199.219 Section 199.219...

  14. 49 CFR 199.219 - Pre-duty use.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Prevention Program § 199.219 Pre-duty use. Each operator shall prohibit a covered employee from using alcohol within four hours prior to performing covered functions, or, if an employee is called to duty to respond... 49 Transportation 3 2010-10-01 2010-10-01 false Pre-duty use. 199.219 Section 199.219...

  15. 22 CFR 19.9 - Pension benefits for former spouses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Pension benefits for former spouses. 19.9 Section 19.9 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.9 Pension benefits for former spouses. ...

  16. 49 CFR 199.105 - Drug tests required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Drug tests required. 199.105 Section 199.105... § 199.105 Drug tests required. Each operator shall conduct the following drug tests for the presence of a prohibited drug: (a) Pre-employment testing. No operator may hire or contract for the use of any...

  17. 49 CFR 199.105 - Drug tests required.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Drug tests required. 199.105 Section 199.105... § 199.105 Drug tests required. Each operator shall conduct the following drug tests for the presence of a prohibited drug: (a) Pre-employment testing. No operator may hire or contract for the use of any...

  18. 49 CFR 199.105 - Drug tests required.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Drug tests required. 199.105 Section 199.105... § 199.105 Drug tests required. Each operator shall conduct the following drug tests for the presence of a prohibited drug: (a) Pre-employment testing. No operator may hire or contract for the use of any...

  19. 49 CFR 199.105 - Drug tests required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Drug tests required. 199.105 Section 199.105... § 199.105 Drug tests required. Each operator shall conduct the following drug tests for the presence of a prohibited drug: (a) Pre-employment testing. No operator may hire or contract for the use of any...

  20. 49 CFR 199.105 - Drug tests required.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Drug tests required. 199.105 Section 199.105... § 199.105 Drug tests required. Each operator shall conduct the following drug tests for the presence of a prohibited drug: (a) Pre-employment testing. No operator may hire or contract for the use of any...

  1. Binding of released Bim to Mcl-1 is a mechanism of intrinsic resistance to ABT-199 which can be overcome by combination with daunorubicin or cytarabine in AML cells

    PubMed Central

    Niu, Xiaojia; Zhao, Jianyun; Ma, Jun; Xie, Chengzhi; Edwards, Holly; Wang, Guan; Caldwell, J. Timothy; Xiang, Shengyan; Zhang, Xiaohong; Chu, Roland; Wang, Zhihong; Lin, Hai; Taub, Jeffrey W.; Ge, Yubin

    2016-01-01

    Purpose To investigate the molecular mechanism underlying intrinsic resistance to ABT-199. Experimental Design Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after ABT-199 treatment alone or in combination with cytarabine or daunorubicin. Immunoprecipitation of Bim and Mcl-1 were used to determine the effect of ABT-199 treatment on their interactions with Bcl-2 family members. Lentiviral shRNA knockdown of Bim and CRISPR knockdown of Mcl-1 were used to confirm their role in resistance to ABT-199. JC-1 assays and flow cytometry were used to determine drug-induced apoptosis. Results Immunoprecipitation of Bim from ABT-199 treated cell lines and a primary patient sample demonstrated decreased association with Bcl-2, but increased association with Mcl-1 without corresponding change in mitochondrial outer membrane potential. ABT-199 treatment resulted in increased levels of Mcl-1 protein, unchanged or decreased Mcl-1 transcript levels, and increased Mcl-1 protein half-life, suggesting that the association with Bim plays a role in stabilizing Mcl-1 protein. Combining conventional chemotherapeutic agent cytarabine or daunorubicin with ABT-199 resulted in increased DNA damage along with decreased Mcl-1 protein levels, compared to ABT-199 alone, and synergistic induction of cell death in both AML cell lines and primary patient samples obtained from AML patients at diagnosis. Conclusions Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML. PMID:27103402

  2. Binding of Released Bim to Mcl-1 is a Mechanism of Intrinsic Resistance to ABT-199 which can be Overcome by Combination with Daunorubicin or Cytarabine in AML Cells.

    PubMed

    Niu, Xiaojia; Zhao, Jianyun; Ma, Jun; Xie, Chengzhi; Edwards, Holly; Wang, Guan; Caldwell, J Timothy; Xiang, Shengyan; Zhang, Xiaohong; Chu, Roland; Wang, Zhihong J; Lin, Hai; Taub, Jeffrey W; Ge, Yubin

    2016-09-01

    To investigate the molecular mechanism underlying intrinsic resistance to ABT-199. Western blots and real-time RT-PCR were used to determine levels of Mcl-1 after ABT-199 treatment alone or in combination with cytarabine or daunorubicin. Immunoprecipitation of Bim and Mcl-1 were used to determine the effect of ABT-199 treatment on their interactions with Bcl-2 family members. Lentiviral short hairpin RNA knockdown of Bim and CRISPR knockdown of Mcl-1 were used to confirm their role in resistance to ABT-199. JC-1 assays and flow cytometry were used to determine drug-induced apoptosis. Immunoprecipitation of Bim from ABT-199-treated cell lines and a primary patient sample demonstrated decreased association with Bcl-2, but increased association with Mcl-1 without corresponding change in mitochondrial outer membrane potential. ABT-199 treatment resulted in increased levels of Mcl-1 protein, unchanged or decreased Mcl-1 transcript levels, and increased Mcl-1 protein half-life, suggesting that the association with Bim plays a role in stabilizing Mcl-1 protein. Combining conventional chemotherapeutic agent cytarabine or daunorubicin with ABT-199 resulted in increased DNA damage along with decreased Mcl-1 protein levels, compared with ABT-199 alone, and synergistic induction of cell death in both AML cell lines and primary patient samples obtained from AML patients at diagnosis. Our results demonstrate that sequestration of Bim by Mcl-1 is a mechanism of intrinsic ABT-199 resistance and supports the clinical development of ABT-199 in combination with cytarabine or daunorubicin for the treatment of AML. Clin Cancer Res; 22(17); 4440-51. ©2016 AACR. ©2016 American Association for Cancer Research.

  3. Identification of a Novel Human Papillomavirus, Type HPV199, Isolated from a Nasopharynx and Anal Canal, and Complete Genomic Characterization of Papillomavirus Species Gamma-12

    PubMed Central

    Oštrbenk, Anja; Kocjan, Boštjan J.; Hošnjak, Lea; Li, Jingjing; Deng, Qiuju; Šterbenc, Anja; Poljak, Mario

    2015-01-01

    The novel human papillomavirus type 199 (HPV199) was initially identified in a nasopharyngeal swab sample obtained from a 25 year-old immunocompetent male. The complete genome of HPV199 is 7,184 bp in length with a GC content of 36.5%. Comparative genomic characterization of HPV199 and its closest relatives showed the classical genomic organization of Gammapapillomaviruses (Gamma-PVs). HPV199 has seven major open reading frames (ORFs), encoding five early (E1, E2, E4, E6, and E7) and two late (L1 and L2) proteins, while lacking the E5 ORF. The long control region (LCR) of 513 bp is located between the L1 and E6 ORFs. Phylogenetic analysis additionally confirmed that HPV-199 clusters into the Gamma-PV genus, species Gamma-12, additionally containing HPV127, HV132, HPV148, HPV165, and three putative HPV types: KC5, CG2 and CG3. HPV199 is most closely related to HPV127 (nucleotide identity 77%). The complete viral genome sequence of additional HPV199 isolate was determined from anal canal swab sample. Two HPV199 complete viral sequences exhibit 99.4% nucleotide identity. To the best of our knowledge, this is the first member of Gamma-PV with complete nucleotide sequences determined from two independent clinical samples. To evaluate the tissue tropism of the novel HPV type, 916 clinical samples were tested using HPV199 type-specific real-time PCR: HPV199 was detected in 2/76 tissue samples of histologically confirmed common warts, 2/108 samples of eyebrow hair follicles, 2/137 anal canal swabs obtained from individuals with clinically evident anal pathology, 4/184 nasopharyngeal swabs and 3/411 cervical swabs obtained from women with normal cervical cytology. Although HPV199 was found in 1.4% of cutaneous and mucosal samples only, it exhibits dual tissue tropism. According to the results of our study and literature data, dual tropism of all Gamma-12 members is highly possible. PMID:26375679

  4. microRNA-199a-3p functions as tumor suppressor by regulating glucose metabolism in testicular germ cell tumors.

    PubMed

    Liu, Xiaowen; Duan, Hongyan; Zhou, Shihua; Liu, Zhiyong; Wu, Daobing; Zhao, Ting; Xu, Shan; Yang, Lifang; Li, Dan

    2016-09-01

    microRNA (miR)-199a-3p serves critical roles in cancer development and progression. In order to improve knowledge of the functional mechanism of miR‑199a‑3p in testicular tumors, the present study characterized the regulation of aerobic glycolysis by miR‑199a‑3p and its impact on metabolism. Using 3‑4,5‑dimethylthiazol‑2‑yl‑2,5 diphenyl tetrazolium bromide, wound healing and flow cytometry assays, it was determined that overexpression of miR‑199a‑3p in Ntera‑2 cells caused suppression of cell growth and migration. Further biochemical methods and high‑throughput quantitative polymerase chain reaction array of metabolic genes showed that inhibition of miR‑199a‑3p markedly elevated lactate production and 12 differentially expressed genes, including 2 upregulated and 10 downregulated genes, were identified following treatment with miR‑199a‑3p in Ntera‑2 cells. In clinical samples, four selected genes, lactate dehydrogenase A, monocarboxylate transporter 1, phosphoglycerate kinase 1 and TP53‑inducible glycolysis and apoptosis regulator, were significantly overexpressed in malignant testicular germ cell tumor, and their expression inversely correlated with the expression of miR‑199a‑3p, suggesting that these four genes may be affected by miR‑199a‑3p. Using bioinformatics analysis, the transcription factor Sp1 binding site was identified in the promoter region of the four selected genes. In addition, miR‑199a‑3p was predicted to bind to conservative target sequences in the 3'‑untranslated region of Sp1 mRNA, suggesting that miR-199a-3p may downregulate these four metabolic genes through Sp1. It was demonstrated the dysregulated expression and activation of miR‑199a‑3p may serve important roles in aerobic glycolysis and tumorigenesis in patients with testicular cancer. Therefore, miR-199a-3p may be a potential biomarker in the prognosis and treatment of testicular tumors.

  5. Adjusting CA19-9 values to predict malignancy in obstructive jaundice: Influence of bilirubin and C-reactive protein

    PubMed Central

    La Greca, Gaetano; Sofia, Maria; Lombardo, Rosario; Latteri, Saverio; Ricotta, Agostino; Puleo, Stefano; Russello, Domenico

    2012-01-01

    AIM: To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ). METHODS: All patients admitted for obstructive jaundice, in the period 2005-2009, were prospectively enrolled in the study, obtaining a total of 102 patients. On admission, all patients underwent complete standard blood test examinations including C-reactive protein (CRP), bilirubin, CA19-9. Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL). The standard cut-off level for CA19-9 was 32 U/mL, whereas for CRP this was 1.5 mg/L. The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value. The patients were divided into 2 groups, MJ and BJ, and after the adjustment a comparison between the 2 groups of patients was performed. Sensitivity, specificity and positive predictive values were calculated before and after the adjustment. RESULTS: Of the 102 patients, 51 were affected by BJ and 51 by MJ. Pathologic CA19-9 levels were found in 71.7% of the patients. In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years), whereas in the MJ group there were 24 (47%) males and 27 (53%) females, with a mean age of 70 years (range 30-92 years). Pathologic CA19-9 serum level was found in 82.3% of MJ. CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ. Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P = 0.000 and P = 0.02), while the CRP level was significantly higher in BJ (P = 0.000). Considering a CA19-9 cut-off level of 32 U/mL, 82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P = 0.002). A CA19-9 cut-off of 100 U/mL increases the difference between the two groups: 35.3% in BJ and 68.6% in MJ (P = 0.0007). Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value (P = 0.003), while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value (P = 0.000004). Sensitivity, specificity, positive predictive values of CA19-9 > 32 U/mL were 82.3%, 45% and 59.1%; when the cut-off was CA19-9 > 100 U/mL they were, respectively, 68.6%, 64.7% and 66%. When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values, these became 49%, 78.4%, 69.4% and 76.5%, 68.6%, 70.9%, respectively. CONCLUSION: The present study proposes CRP as a new and useful correction factor to improve the diagnostic value of the CA19-9 tumor marker in patients with cholestatic jaundice. PMID:22919247

  6. 46 CFR 199.153 - Survival craft launching and recovery arrangements using falls and a winch.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... falls and a winch. 199.153 Section 199.153 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Requirements for All Vessels § 199.153 Survival craft launching and recovery arrangements using falls and a... appliances for free-fall launching arrangements, from a position within the survival craft. (b) Each fall...

  7. 46 CFR 199.153 - Survival craft launching and recovery arrangements using falls and a winch.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... falls and a winch. 199.153 Section 199.153 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Requirements for All Vessels § 199.153 Survival craft launching and recovery arrangements using falls and a... appliances for free-fall launching arrangements, from a position within the survival craft. (b) Each fall...

  8. 46 CFR 199.153 - Survival craft launching and recovery arrangements using falls and a winch.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... falls and a winch. 199.153 Section 199.153 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Requirements for All Vessels § 199.153 Survival craft launching and recovery arrangements using falls and a... appliances for free-fall launching arrangements, from a position within the survival craft. (b) Each fall...

  9. Historical Records of Mercury Stable Isotopes in Sediments of Tibetan Lakes

    NASA Astrophysics Data System (ADS)

    Yin, Runsheng; Feng, Xinbin; Hurley, James P.; Krabbenhoft, David P.; Lepak, Ryan F.; Kang, Shichang; Yang, Handong; Li, Xiangdong

    2016-03-01

    The Tibetan Plateau (TP), known as the “Third Pole”, is a critical zone for atmospheric mercury (Hg) deposition. Increasing anthropogenic activities in the globe leads to environmental changes, which may affect the loading, transport and deposition of Hg in the environment. However, the deposition history and geochemical cycling of Hg in the TP is still uncertain. Our records of Hg and Hg isotopes in sediment profiles of the two largest lakes in the TP, Lake Qinghai and Nam Co, show increased Hg influx since last century, with the maximum Hg influx enrichment ratios of 5.4 and 3.5 in Lake Qinghai and Nam Co, respectively. Shifts in negative δ 202Hg in Lake Qinghai (-4.55 to -3.15‰) and Nam Co (-5.04 to -2.16‰) indicate increased atmospheric Hg deposition through rainfall, vegetation and runoff of soils. Mass independent fractionation of both even-Hg (∆ 200Hg: +0.05 to +0.10‰) and odd-Hg (∆ 199Hg: +0.12 to +0.31‰) isotopes were observed. Positive Δ 200Hg suggest high proportion of precipitation-derived Hg in the TP, whereas the positive Δ 199Hg results from Hg(II) photo-reduction. Both lakes show increasing Δ 199Hg since the 1900 s, and we conclude that with the decrease of ice duration, Hg(II) photo-reduction may have been accelerated in these TP lakes.

  10. Historical Records of Mercury Stable Isotopes in Sediments of Tibetan Lakes.

    PubMed

    Yin, Runsheng; Feng, Xinbin; Hurley, James P; Krabbenhoft, David P; Lepak, Ryan F; Kang, Shichang; Yang, Handong; Li, Xiangdong

    2016-03-21

    The Tibetan Plateau (TP), known as the "Third Pole", is a critical zone for atmospheric mercury (Hg) deposition. Increasing anthropogenic activities in the globe leads to environmental changes, which may affect the loading, transport and deposition of Hg in the environment. However, the deposition history and geochemical cycling of Hg in the TP is still uncertain. Our records of Hg and Hg isotopes in sediment profiles of the two largest lakes in the TP, Lake Qinghai and Nam Co, show increased Hg influx since last century, with the maximum Hg influx enrichment ratios of 5.4 and 3.5 in Lake Qinghai and Nam Co, respectively. Shifts in negative δ (202)Hg in Lake Qinghai (-4.55 to -3.15‰) and Nam Co (-5.04 to -2.16‰) indicate increased atmospheric Hg deposition through rainfall, vegetation and runoff of soils. Mass independent fractionation of both even-Hg (∆ (200)Hg: +0.05 to +0.10‰) and odd-Hg (∆ (199)Hg: +0.12 to +0.31‰) isotopes were observed. Positive Δ (200)Hg suggest high proportion of precipitation-derived Hg in the TP, whereas the positive Δ (199)Hg results from Hg(II) photo-reduction. Both lakes show increasing Δ (199)Hg since the 1900 s, and we conclude that with the decrease of ice duration, Hg(II) photo-reduction may have been accelerated in these TP lakes.

  11. WAVE2 targeting to phosphatidylinositol 3,4,5-triphosphate mediated by insulin receptor substrate p53 through a complex with WAVE2.

    PubMed

    Takahashi, Kazuhide; Suzuki, Katsuo

    2010-11-01

    Membrane targeting of WAVE2 along microtubules to phosphatidylinositol 3,4,5-triphosphate (PIP(3)) in response to an extracellular stimulus requires Rac1, Pak1, stathmin, and EB1. However, whether WAVE2 interacts directly with PIP(3) or not remains unclear. We demonstrate that insulin-like growth factor I (IGF-I) induces WAVE2 membrane targeting, accompanied by phosphorylation of Pak1 at serine 199/204 (Ser199/204) and stathmin at Ser38 in the inner cytoplasmic region. This is spatially independent of the membrane region where the IGF-I receptor (IGF-IR) is locally activated. WAVE2, phosphorylated Pak1, and phosphorylated stathmin located at the microtubule ends began to accumulate at the leading edge of cells in close proximity to PIP(3) that was produced in a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent manner. The PIP(3)-beads binding assay revealed that insulin receptor substrate p53 (IRSp53) and actin rather than WAVE2 bound to PIP(3). IRSp53 constitutively associated with WAVE2 and these two proteins colocalized with PIP(3) at the leading edge after IGF-I stimulation. Suppression of IRSp53 expression by two independent small interfering RNAs (siRNAs) completely inhibited IGF-I-induced membrane targeting and local accumulation of WAVE2 at the leading edge of cells. We propose that IRSp53 constitutively forms a complex with WAVE2 and is crucial for membrane targeting followed by local accumulation of WAVE2 at the leading edge of cells through linking WAVE2 to PIP(3) that is produced near locally activated IGF-IR in response to IGF-I. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  12. Comparison of different fertilisation media for an in vitro maturation?fertilisation?culture system using flow-cytometrically sorted X chromosome-bearing spermatozoa for bovine embryo production.

    PubMed

    Ferré, Luis B; Bogliotti, Yanina; Chitwood, James L; Fresno, Cristóbal; Ortega, Hugo H; Kjelland, Michael E; Ross, Pablo J

    2015-05-13

    High demand exists among commercial cattle producers for in vitro-derived bovine embryos fertilised with female sex-sorted spermatozoa from high-value breeding stock. The aim of this study was to evaluate three fertilisation media, namely M199, synthetic oviductal fluid (SOF) and Tyrode's albumin-lactate-pyruvate (TALP), on IVF performance using female sex-sorted spermatozoa. In all, 1143, 1220 and 1041 cumulus-oocyte complexes were fertilised in M199, SOF and TALP, respectively. There were significant differences among fertilisation media (P < 0.05) in cleavage rate (M199 = 57%, SOF = 71% and TALP = 72%), blastocyst formation (M199 = 9%, SOF = 20% and TALP = 19%), proportion of Grade 1 blastocysts (M199 = 15%, SOF = 52% and TALP = 51%), proportion of Grade 3 blastocysts (M199 = 58%, SOF = 21% and TALP = 20%) and hatching rates (M199 = 29%, SOF = 60% and TALP = 65%). The inner cell mass (ICM) and trophectoderm (TE) cells of Day 7 blastocysts were also affected by the fertilisation medium. Embryos derived from SOF and TALP fertilisation media had higher numbers of ICM, TE and total cells than those fertilised in M199. In conclusion, fertilisation media affected cleavage rate, as well as subsequent embryo development, quality and hatching ability. SOF and TALP fertilisation media produced significantly more embryos of higher quality than M199.

  13. 49 CFR 199.223 - Refusal to submit to a required alcohol test.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... required alcohol test. Each operator shall require a covered employee to submit to a post-accident alcohol test required under § 199.225(a), a reasonable suspicion alcohol test required under § 199.225(b), or a... 49 Transportation 3 2010-10-01 2010-10-01 false Refusal to submit to a required alcohol test. 199...

  14. 49 CFR 199.223 - Refusal to submit to a required alcohol test.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... required alcohol test. Each operator shall require a covered employee to submit to a post-accident alcohol test required under § 199.225(a), a reasonable suspicion alcohol test required under § 199.225(b), or a... 49 Transportation 3 2011-10-01 2011-10-01 false Refusal to submit to a required alcohol test. 199...

  15. 49 CFR 199.223 - Refusal to submit to a required alcohol test.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... required alcohol test. Each operator shall require a covered employee to submit to a post-accident alcohol test required under § 199.225(a), a reasonable suspicion alcohol test required under § 199.225(b), or a... 49 Transportation 3 2014-10-01 2014-10-01 false Refusal to submit to a required alcohol test. 199...

  16. 49 CFR 199.223 - Refusal to submit to a required alcohol test.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... required alcohol test. Each operator shall require a covered employee to submit to a post-accident alcohol test required under § 199.225(a), a reasonable suspicion alcohol test required under § 199.225(b), or a... 49 Transportation 3 2012-10-01 2012-10-01 false Refusal to submit to a required alcohol test. 199...

  17. 49 CFR 199.223 - Refusal to submit to a required alcohol test.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... required alcohol test. Each operator shall require a covered employee to submit to a post-accident alcohol test required under § 199.225(a), a reasonable suspicion alcohol test required under § 199.225(b), or a... 49 Transportation 3 2013-10-01 2013-10-01 false Refusal to submit to a required alcohol test. 199...

  18. The roles of serum and urinary carbohydrate antigen 19-9 in the management of patients with antenatal hydronephrosis.

    PubMed

    Atar, Arda; Oktar, Tayfun; Kucukgergin, Canan; Kalelioglu, Ibrahim; Seckin, Sule; Ander, Haluk; Ziylan, Orhan; Kadioglu, Teoman Cem

    2015-06-01

    Serum carbohydrate antigen (CA) 19-9 has been clinically applied as a valuable tumor marker for pancreatic and gastrointestinal carcinoma. CA 19-9 is expressed in normal excretory epithelium tissues. Increased CA 19-9 has also been observed in uroepithelial tumors as well as in nonmalignant conditions including hydronephrosis secondary to ureteral stones. The purpose of this article is to evaluate the role of urinary CA 19-9 as a non-invasive biomarker in the postnatal differentiation of obstructive and non-obstructive hydronephrosis in patients with unilateral antenatal hydronephrosis. Infants with isolated renal pelvic dilatation, defined as the presence of anteroposterior pelvic diameter (APPD) equal to or greater than 7 mm based on antenatal ultrasound after 28 weeks' gestation, underwent systematic investigation for uropathies and were prospectively followed up. The pyeloplasty group consisted of 17 patients with ureteropelvic junction (UPJ) obstruction who had undergone pyeloplasty. The non-obstructive dilatation (NOD) group consisted of 17 patients with non-obstructive hydronephrosis, and the control group consisted of 21 healthy children. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure the urinary and serum CA 19-9 levels. In both hydronephrosis groups (pyeloplasty and non-obstructive dilatation), the correlations between urinary and serum CA 19-9 levels with the anteroposterior pelvic diameter measured at the third trimester and the postnatal initial evaluation and differential renal function were investigated. The initial median urinary CA 19-9 levels were significantly greater in children who underwent pyeloplasty than in both the non-obstructive hydronephrosis (143 ± 38 vs. 68 ± 23, respectively; p = 0.007) and the healthy control groups (143 ± 38 vs. 13 ± 3, respectively; p = 0.001) (Figure). Three months after surgery, the urinary CA 19-9 levels had decreased significantly according to the preoperative levels in the pyeloplasty group (143 ± 38 vs. 55 ± 16, p = 0.039). In both the pyeloplasty and NOD groups, there was a correlation of urinary CA 19-9 levels with differential renal function and a correlation of serum CA 19-9 levels with the initial anteroposterior pelvic diameter. Receiver operator characteristic (ROC) analysis revealed a better diagnostic profile for the urinary CA 19-9 level than for the serum CA 19-9 level in terms of identifying obstruction in the hydronephrosis groups (areas under the curve = 0.8 and 0.7, respectively). The best cut-off value of for urinary CA 19-9 was 85.5 U/mL with 76% sensitivity, 85% specificity. The negative predictive value was 80%. The results suggest that voided urine CA 19-9 levels seems to be a more useful marker than serum CA 19-9 in obstructive dilatation. An appropriate decrease in urinary CA 19-9 levels after pyeloplasty may be used as a predictor of surgical outcome. In addition, the results have a number of important diagnostic implications that should be further validated in a larger study population. Based on these results, we suggest that a high urinary CA 19-9 level is a non-invasive clinically applicable marker for differentiating between obstruction and non-obstructive dilatation. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

  19. Downregulation of miR-199b promotes the acute spinal cord injury through IKKβ-NF-κB signaling pathway activating microglial cells

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

    Zhou, Heng-Jun; Wang, Li-Qing; Xu, Qing-Sheng

    Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase β-nuclear factor-kappa B (IKKβ-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKβ/NF-κB weremore » observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKβ by targeting its 3′- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKβ, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1β. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKβ-NF-κB signaling pathway and TNF-α and IL-1β. These results indicated that miR-199b attenuated ASCI at least partly through IKKβ-NF-κB signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury. - Highlights: • Downregulation of miR-199b and activation of IKKβ/NF-κB were observed in rat after SCI. • miR-199b negatively regulated IKKβ by targeting its 3′-UTR. • miR-199b overexpression reversed the increasing IKKβ, p-p65, TNF-α and IL-1β in LPS-treated BV2. • BMS-345541 reversed the up-regulation of TNF-α and IL-1β induced by miR-199b inhibitor. • Overexpression of miR-199b attenuated ASCI and decreased the expression of IKKβ-NF-κB in rats.« less

  20. [Regulation of microRNA-199a on adhesion, migration and invasion ability of human endometrial stromal cells].

    PubMed

    Dai, Lan; Gu, Li-ying; Zhu, Jie; Shi, Jun; Wang, Yao; Ji, Fang; Di, Wen

    2011-11-01

    To study the regulation of microRNA 199a (miR-199a) on adhesion, migration and invasion ability of human eutopic endometrial stromal cells (ESC) from patients with endometriosis. ESC were transfected with miR-199a mimics or negative control (NC) RNA by lipofectamine 2000. The adhesion, migration and invasion ability of ESC were detected by cell adhesion assay, scratch assay, cell migration assay and matrigel invasion assay, respectively. Luciferase reporter assay was used to evaluate whether IKKβ was the target gene of miR-199a. The expression of ikappa B kinase beta (IKKβ), inhibitory kappa B alpha (IκB-α), phospho-IκB-α(p-IκB-α) and nuclear factor-kappa B (NF-κB) protein were measured by western blot. (1) Adhesion potential: the adhesion inhibitory rates were (14 ± 4)% in miR-199a group and 0 in control group, which showed significant difference (P < 0.01). (2) Migration and invasion: in the scratch assay, ESC transfected with miR-199a exhibited a lower scratch closure rate than that of controls. In migration and invasion assays, the migration and invasion ability of miR-199a group were significantly decreased compared with those of NC group [130 ± 31 vs. 247 ± 36 (P < 0.01); 63 ± 15 vs. 133 ± 17 (P < 0.01), respectively]. (3) The luciferase activity of miR-199a group was significantly lowered than that of control group [0.160 ± 0.006 vs. 0.383 ± 0.083 (P < 0.01)]. The protein levels of IKKβ, p-IκB-α, IκB-α and NF-κB of 0.350 ± 0.195, 0.443 ± 0.076, 1.970 ± 0.486 and 0.454 ± 0.147 in miR-199a group were significantly different compared with the NC group in which the protein levels were set at 1.000 (P < 0.01). miR-199a can inhibit the adhesion, migration and invasion of the ESC. IKKβ is the target gene of miR-199a in ESC. One of the mechanisms of the inhibition effect is probably that miR-199a inhibits the activation of NF-κB signaling pathway by targeting IKKβ gene.

  1. 49 CFR 40.199 - What problems always cause a drug test to be cancelled?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false What problems always cause a drug test to be cancelled? 40.199 Section 40.199 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.199 What problems always cause a drug test to be cancelled? (a...

  2. Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1.

    PubMed

    Zhou, QiQi; Yang, Liuqing; Larson, Scott; Basra, Sapreet; Merwat, Shehzad; Tan, Alai; Croce, Carlo; Verne, G Nicholas

    2016-05-01

    Many patients with irritable bowel syndrome IBS not only have abdominal pain but also may suffer from visceral hypersensitivity and heighted visceral nociception. Moreover, IBS has few effective therapeutic agents and mechanisms of disease are unclear. Our goals were to (i) identify microRNA (miRNA) expression, signalling and targets in human colon (controls; patients with IBS); (ii) verify in vitro, IBS-associated changes in miRNAs, especially miR-199, which is complementary to the transient receptor potential vanilloid type 1 (TRPV1) gene; and (iii) determine whether modulating the expression of miRNAs in vivo, especially miR-199, reverses associated changes and pathological hallmarks of visceral hypersensitivity via TRPV1 signalling. We evaluated 45 patients with diarrhoea-predominant IBS (IBS-D) and 40 controls with (1) visceral pain severity score and (2) colonoscopy with biopsies. miRNA expression was evaluated in human colon following miRNA array analysis. Luciferase assays were done to confirm relationships between miR-199 and TRPV1 expression. A rat model of visceral hypersensitivity was used to study miR-199 and its target gene (TRPV1) expression in dorsal root ganglion (DRG) and colon in vivo. Gut miR-199a/b expression in IBS-D was significantly decreased, which correlated directly with both increased visceral pain scores and TRPV1 expression. In vivo upregulation of miR-199a by intraperitoneal injection of lenti-miR-199a precursors decreased visceral hypersensitivity via diminished TRPV1 signalling. Decreased colonic miR-199a/b correlates with visceral pain in patients with IBS-D. Similarly, reduced miR-199a expression in rat DRG and colon tissue is associated with heightened visceral hypersensitivity. In vivo upregulation of miR-199a decreases visceral pain via inhibition of TRPV1 signalling. Thus, miR-199 precursors may be promising therapeutic candidates for the treatment in patients with visceral pain. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer

    PubMed Central

    Aldakkak, Mohammed; Christians, Kathleen K; Krepline, Ashley N; George, Ben; Ritch, Paul S; Erickson, Beth A; Johnston, Fabian M; Evans, Douglas B; Tsai, Susan

    2015-01-01

    Background The prognostic value of CA19-9 in patients with pancreatic cancer (PC) treated with neoadjuvant therapy has not been well described. Methods Pre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36–200), moderate (201–1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery. Results Pre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group (P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups (P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02]. Conclusions Among patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic. PMID:26255895

  4. Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.

    PubMed

    Sun, Dawei; Han, Shen; Liu, Chao; Zhou, Rui; Sun, Weihai; Zhang, Zhijun; Qu, Jianjun

    2016-04-11

    BACKGROUND The objective of this study was to explore the role of miR-199a-5p in the development of thyroid cancer, including its anti-proliferation effect and downstream signaling pathway. MATERIAL AND METHODS We conducted qRT-PCR analysis to detect the expressions of several microRNAs in 42 follicular thyroid carcinoma patients and 42 controls. We identified CTGF as target of miR-491, and viability and cell cycle status were determined in FTC-133 cells transfected with CTGF siRNA, miR-199a mimics, or inhibitors. RESULTS We identified an underexpression of miR-199a-5p in follicular thyroid carcinoma tissue samples compared with controls. Then we confirmed CTGF as a target of miR-199a-5p thyroid cells by using informatics analysis and luciferase reporter assay. Additionally, we found that mRNA and protein expression levels of CTGF were both clearly higher in malignant tissues than in benign tissues. miR-199a-5p mimics and CTGF siRNA similarly downregulated the expression of CTGF, and reduced the viability of FTC-133 cells by arresting the cell cycle in G0 phase. Transfection of miR-199a-5p inhibitors increased the expression of CTGF and promoted the viability of the cells by increasing the fraction of cells in G2/M and S phases. CONCLUSIONS Our study proves that the CTGF gene is a target of miR-199a-5p, demonstrating the negatively related association between CTGF and miR-199a. These findings suggest that miR-199a-5p might be a novel therapeutic target in the treatment of follicular thyroid carcinoma.

  5. Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis.

    PubMed

    Maged, Ahmed M; Deeb, Wesam S; El Amir, Azza; Zaki, Sherif S; El Sawah, Heba; Al Mohamady, Maged; Metwally, Ahmed A; Katta, Maha A

    2018-04-01

    To evaluate the value of serum microRNA-122 (miR-122) and miR-199a as reliable noninvasive biomarkers in the diagnosis of endometriosis. During 2015-2016, at a teaching hospital in Egypt, a prospective cohort study was conducted on 45 women with pelvic endometriosis and 35 women who underwent laparoscopy for pelvic pain but were not diagnosed with endometriosis. Blood and peritoneal fluid (PF) samples were collected; interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay and miR-122 and miR-199a expression was measured by quantitative real-time polymerase chain reaction. The serum and PF levels of IL-6, miR-122, and miR-199a were significantly higher in women with endometriosis than in controls (P<0.001 for all comparisons). Serum miR-122 expression was positively correlated with serum IL-6 (r=0.597), PF IL-6 (r=0.603), PF miR-122 (r=0.934), serum miR-199a (r=0.727), and PF miR-199a (r=0.653). Serum miR-199a expression was positively correlated with serum IL-6 (r=0.677), PF IL-6 (r=0.678), PF miR-122 (r=0.744), and PF miR-199a (r=0.932). Serum miR-122 and miR-199a had a sensitivity of 95.6% and 100.0%, and a specificity of 91.4% and 100%, respectively, for the detection of endometriosis. Serum miR-122 and miR-199a were significantly increased in endometriosis, indicating that these microRNAs might serve as biomarkers for the diagnosis of endometriosis. © 2017 International Federation of Gynecology and Obstetrics.

  6. 46 CFR 199.05 - Incorporation by reference.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Acceptance of Prototype Novel Life-saving Appliances and Arrangements, 17 November 1983 199.40 Resolution A.657(16), Instructions for Action in Survival Craft, 19 November 1989 199.175 Resolution A.658(16), Use...

  7. Techniques used to search for a permanent electric dipole moment of the 199Hg atom and the implications for CP violation

    NASA Astrophysics Data System (ADS)

    Swallows, M. D.; Loftus, T. H.; Griffith, W. C.; Heckel, B. R.; Fortson, E. N.; Romalis, M. V.

    2013-01-01

    We discuss in detail the search for a permanent electric dipole moment (EDM) of the 199Hg atom reported by Griffith [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.102.101601 102, 101601 (2009)]. The upper bound, d(199Hg)<3.1×10-29 e cm (95% C.L.), is a factor of 7 improvement over the best previous EDM limit for 199Hg, provides the most sensitive probe to date for EDMs in diamagnetic atoms, and sets new limits on time-reversal symmetry violation in extensions to the standard model. This paper provides extensive discussion of the techniques used to search for the 199Hg EDM and the implications of the new 199Hg EDM limit for CP violation in elementary particle interactions.

  8. Association between serum CA 19-9 and metabolic syndrome: A cross-sectional study.

    PubMed

    Du, Rui; Cheng, Di; Lin, Lin; Sun, Jichao; Peng, Kui; Xu, Yu; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Lu, Jieli; Ning, Guang

    2017-11-01

    Increasing evidence suggests that serum CA 19-9 is associated with abnormal glucose metabolism. However, data on the association between CA 19-9 and metabolic syndrome is limited. The aim of the present study was to investigate the association between serum CA 19-9 and metabolic syndrome. A cross-sectional study was conducted on 3641 participants aged ≥40 years from the Songnan Community, Baoshan District in Shanghai, China. Logistic regression analysis was used to evaluate the association between serum CA 19-9 and metabolic syndrome. Multivariate logistic regression analysis showed that compared with participants in the first tertile of serum CA 19-9, those in the second and third tertiles had increased odds ratios (OR) for prevalent metabolic syndrome (multivariate adjusted OR 1.46 [95% confidence interval {CI} 1.11-1.92] and 1.51 [95% CI 1.14-1.98]; P trend  = 0.005). In addition, participants with elevated serum CA 19-9 (≥37 U/mL) had an increased risk of prevalent metabolic syndrome compared with those with serum CA 19-9 < 37 U/mL (multivariate adjusted OR 2.10; 95% CI 1.21-3.65). Serum CA 19-9 is associated with an increased risk of prevalent metabolic syndrome. In order to confirm this association and identify potential mechanisms, prospective cohort and mechanic studies should be performed. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  9. Inhibition of Mcl-1 enhances cell death induced by the Bcl-2-selective inhibitor ABT-199 in acute myeloid leukemia cells.

    PubMed

    Luedtke, Daniel A; Niu, Xiaojia; Pan, Yihang; Zhao, Jianyun; Liu, Shuang; Edwards, Holly; Chen, Kang; Lin, Hai; Taub, Jeffrey W; Ge, Yubin

    2017-01-01

    Acute myeloid leukemia (AML) is a serious disease. The 5-year survival rates remain frustratingly low (65% for children and 26% for adults). Resistance to frontline chemotherapy (usually cytarabine) often develops; therefore a new treatment modality is needed. Bcl-2 family proteins play an important role in balancing cell survival and apoptosis. The antiapoptotic Bcl-2 family proteins have been found to be dysregulated in AML. ABT-199, a BH3 mimetic, was developed to target antiapoptotic protein Bcl-2. Although ABT-199 has demonstrated promising results, resistance occurs. Previous studies in AML show that ABT-199 alone decreases the association of proapoptotic protein Bim with Bcl-2, but this is compensated by increased association of Bim with prosurvival protein Mcl-1, stabilizing Mcl-1, resulting in resistance to ABT-199. In this study, we investigated the antileukemic activity of the Mcl-1-selective inhibitor A-1210477 in combination with ABT-199 in AML cells. We found that A-1210477 synergistically induced apoptosis with ABT-199 in AML cell lines and primary patient samples. The synergistic induction of apoptosis was decreased upon Bak, Bax and Bim knockdown. While A-1210477 treatment alone also increased Mcl-1 protein levels, combination with ABT-199 reduced binding of Bim to Mcl-1. Our results demonstrate that sequestration of Bim by Mcl-1, a mechanism of ABT-199 resistance, can be abrogated by combined treatment with the Mcl-1 inhibitor A-1201477.

  10. Decrement of miR-199a-5p contributes to the tumorigenesis of bladder urothelial carcinoma by regulating MLK3/NF-κB pathway

    PubMed Central

    Song, Tao; Zhang, Xu; Yang, Guoqiang; Song, Yong; Cai, Wei

    2015-01-01

    Aberrant miRNA expression is implicated in tumorigenesis. However, the role of miRNAs in bladder urothelial carcinoma still remains largely unknown. In this study, miR-199a-5p was validated to be significantly down-regulated in bladder urothelial carcinoma. In addition, restoring expression of miR-199a-5p inhibited the tumorigenesis of bladder urothelial carcinoma in vitro and in vivo by inducing the apoptosis and suppressing the proliferation of bladder cancerous cells. Further investigation reported that MLK3 was a direct target of miR-199a-5p. Moreover, the expression level of miR-199a-5p was conversely correlated with MLK3 in bladder cancerous cells. In addition, reintroduction of MLK3 was identified to promote the proliferation and inhibit the apoptotic rate of cells, which have been altered by miR-199a-5p through activating the NF-κB pathway. All together, decrement of miR-199a-5p contributes to the tumorigenesis of bladder cancer by directly regulating MLK3/NF-κB pathway and miR-199a-5p might be developed as a therapeutic target for treatment of the bladder urothelial carcinoma. PMID:26885275

  11. Release of lysosomal enzymes in Candida albicans phagocytosis by rat peritoneal macrophages.

    PubMed

    Fontenla de Petrino, S E; Sirena, A

    1984-02-15

    The present paper reports the in vitro release of lysosomal enzymes in the supernatant of cultures of rat peritoneal macrophages, with the addition of Candida albicans cells. Macrophages were taken from the rat peritoneal cavity 72 hr after non-specific activation with Brain-Heart-Infusion (B.H.I.) broth containing 10% proteose-peptone No. 3. They were then cultured in Parker medium No. 199 (TC 199). After 24 hr a suspension of Candida albicans cells, in a determined concentration, was added to the peritoneal macrophage cultures. At that time, and during pre-determined periods, the following enzymes in the culture supernatants were studied using colorimetric methods: beta-glucuronidase, beta-galactosidase and acid phosphatase. It is concluded that, under identical conditions, the release of beta-galactosidase and acid phosphatase is higher than for beta-glucuronidase. The release rate of all three enzymes is the highest at a 6 hr incubation period, after which, a gradual decrease leads to the rate down to 50% at 24 hr.

  12. E-Health Literacy and Health Information Seeking Behavior Among University Students in Bangladesh.

    PubMed

    Islam, Md Mohaimenul; Touray, Musa; Yang, Hsuan-Chia; Poly, Tahmina Nasrin; Nguyen, Phung-Anh; Li, Yu-Chuan Jack; Syed Abdul, Shabbir

    2017-01-01

    Web 2.0 has become a leading health communication platform and will continue to attract young users; therefore, the objective of this study was to understand the impact of Web 2.0 on health information seeking behavior among university students in Bangladesh. A random sample of adults (n = 199, mean 23.75 years, SD 2.87) participated in a cross-sectional, a survey that included the eHealth literacy scale (eHEALS) assessed use of Web 2.0 for health information. Collected data were analyzed using a descriptive statistical method and t-tests. Finally logistic regression analyses were conducted to determine associations between sociodemographic, social determinants, and use of Web 2.0 for seeking and sharing health information. Almost 74% of older Web 2.0 users (147/199, 73.9%) reported using popular Web 2.0 websites, such as Facebook and Twitter, to find and share health information. Current study support that current Web-based health information seeking and sharing behaviors influence health-related decision making.

  13. MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma.

    PubMed

    Zhang, Wei; Qian, Sheng; Yang, Guowei; Zhu, Liang; Zhou, Bo; Wang, Jianhua; Liu, Rong; Yan, Zhiping; Qu, Xudong

    2018-06-15

    Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and shows rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Regulators of G-protein signaling (RGS) are critical for defining G-protein-dependent signal fidelity. RGS17 plays an important role in the regulation of cancer cell proliferation, migration and invasion. Here, we showed that miR-199 was downregulated in a hepatocarcinoma cell line. Overexpression of miR-199 significantly suppressed HCC cell proliferation, migration, and invasion in vitro. RGS17 overexpression promoted HCC cell proliferation, migration, and invasion, and reversed the miR-199 mediated inhibition of proliferation, migration, and invasion. Dual-fluorescence reporter experiments confirmed that miR-199 downregulated RGS17 by direct interaction with the 3'-UTR of RGS17 mRNA. In vivo studies showed that miR-199 overexpression significantly inhibited the growth of tumors. Taken together, the results suggested that miR-199 inhibited tumor growth and metastasis by targeting RGS17. Published by Elsevier B.V.

  14. Childhood lead poisoning from the smelter in Torreon, Mexico

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

    Soto-Jimenez, Martin F., E-mail: martin@ola.icmyl.unam.mx; Flegal, Arthur R.

    2011-05-15

    Lead concentrations and isotopic compositions in blood samples of 34 children (ages 2-17 years) living within a 113 km{sup 2} area of a silver-zinc-lead smelter plant in Torreon, Mexico were compared to those of associated environmental samples (soil, aerosols, and outdoor and indoor dust) to identify the principal source(s) of environmental and human lead contamination in the area. Lead concentrations of soil and outdoor dust ranged 130-12,050 and 150-14,365 {mu}g g{sup -1}, respectively. Concentrations were greatest near the smelter, with the highest levels corresponding with the prevailing wind direction, and orders of magnitude above background concentrations of 7.3-33.3 {mu}g g{supmore » -1}. Atmospheric lead depositions in the city varied between 130 and 1350 {mu}g m{sup -2} d{sup -1}, again with highest rates <1 km from the smelter. Blood lead (PbB) concentrations (11.0{+-}5.3 {mu}g dl{sup -1}) levels in the children ranged 5.0-25.8 {mu}g dl{sup -1}, which is 3-14 times higher than the current average (1.9 {mu}g dl{sup -1}) of children (ages 1-5 years) in the US. Lead isotopic ratios ({sup 206}Pb/{sup 207}Pb, {sup 208}Pb/{sup 207}Pb) of the urban dust and soil (1.200{+-}0.009, 2.467{+-}0.003), aerosols (1.200{+-}0.002, 2.466{+-}0.002), and PbB (1.199{+-}0.001, 2.468{+-}0.002) were indistinguishable from each other, as well as those of the lead ores processed at the smelter (1.199{+-}0.007, 2.473{+-}0.007). Consequently, an elevated PbB concentrations of the children in Torreon, as well as in their environment, are still dominated by industrial emissions from the smelter located within the city, in spite of new controls on atmospheric releases from the facility. - Highlights: {yields} Pb contents in environmental samples evidenced chronic Pb pollution in Torreon. {yields} Pb stable isotopes evidenced contemporary emissions from the Ag-Cod-Pb-Zn smelter. {yields} Pb urban dust and soil account for most of the childhood lead poisoning in Torreon.{yields} Levels of Pub in Torreon's children are 3-14 times higher than children in the US.{yields} Children Pub concentrations are primarily attributed to emissions from the smelter.« less

  15. Comparison of tumor markers and clinicopathological features in serous and mucinous borderline ovarian tumors.

    PubMed

    Alanbay, I; Aktürk, E; Coksuer, H; Ercan, C M; Karaşahin, E; Dede, M; Yenen, M C; Ozan, H; Dilek, S

    2012-01-01

    The aim of this study was to assess tumor markers and clinicopathological findings of patients with serous and mucinous borderline ovarian tumor (BOT) features. The study consisted of 50 patients that were diagnosed with and treated for BOT between 2005-2010 in three centers. CA125, CA19-9, and CA125+CA19-9 levels and clinicopathological features were compared in serous and mucinous histotypes. In serous and mucinous BOTs, correlations between tumor markers and demographics such as age, menopausal status, parity, clinical findings (stage, relapse, adjuvant chemotherapy, cytology, lymph node involvement and tumoral morphology (cystic-solid content, papilla, septation) were evaluated. There were no significant differences between serous and mucinous tumors in the clinicopathological features such as stage, tumor markers, age, menopausal status, or cytology. In serous BOTs we found a significant relation between elevated CA125+ CA19-9, CA19-9 and recurrence (p < 0.05). Also there was a significant relation between elevated CA125+ CA19-9, CA19-9 and cytology positivity (p < 0.05). We found a significant relation in serous BOTs between elevated CA125+CA19-9, adjuvant chemotherapy and lymph node metastases (p < 0.05). Also In mucinous BOTs with papilla formation we found a significant relation between elevated CA125 and CA125+ CA19-9 (p < 0.05). There was significant relation between cytology positivity and elevated CA19-9 in mucinous BOTs (p < 0.05). Serum tumor markers of serous and mucinous BOTs were different in relation to their clinicopathological features. This may reflect differences of serous and mucinous BOTs.

  16. The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas

    PubMed Central

    Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

    2016-01-01

    Introduction Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. Aim The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. Materials and Methods This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn’t warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Results Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple’s procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Conclusion Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn’t predict vascular involvement and liver metastasis. PMID:27134925

  17. The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas.

    PubMed

    Pandiaraja, Jayabal; Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

    2016-03-01

    Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn't warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple's procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn't predict vascular involvement and liver metastasis.

  18. Insect repellent plants traditional usage practices in the Ethiopian malaria epidemic-prone setting: an ethnobotanical survey

    PubMed Central

    2014-01-01

    Background The usage of insect repellent plants (IRPs) is one of the centuries-old practices in Africa. In Ethiopia, malaria remains a leading cause of morbidity and mortality, subsequently the majority of people have a tendency to apply various plants as repellents to reduce or interrupt the biting activity of insects. Accordingly, this survey was undertaken to document and evaluate knowledge and usage practices of the local inhabitants on IRPs in the malaria epidemic-prone setting of Ethiopia. Methods Ethnobotanical survey was conducted between January and May 2013. Selected 309 household members were interviewed by administering pre-tested questionnaire on knowledge and usage practices of repellent plants, in Bechobore Kebele, Jimma Zone, Ethiopia. Results Overall, 70.2% (217/309) and 91.8% (199/217) of the respondents have had ample awareness and usage practices of repellent plants, respectively. Informants cited about twenty-two plant species as repellents and also indicated that these plants are useful(85.5%), accessible(86.8%), and affordable(83.9%) too. Residents mainly applying dried leaves [93.9% (187/199)] by means of burning/smouldering [98.9% (197/199)] with the traditional charcoal stove to repel insects, primarily mosquitoes. About 52.8% (105/199) of the informants using aproximately15g of dried plant-materials every day. A Chi-square analysis shows statistically a significant link between the knowledge on repellent plants and gender as well as average monthly income although not with the age of the respondents. Nevertheless, the repellent plant usage custom was not significantly associated with gender, monthly income, and age of the informants. Conclusion Though most of the people have had an adequate awareness still a sizable faction of society suffers with deprivation of IRPs knowledge and usage practices. Therefore, this study calls for more surveys to conserve the existing indigenous knowledge and cultural practices. It could lay the first stone to develop the next generation cost-effective vector control tools in the near future. PMID:24521138

  19. Insect repellent plants traditional usage practices in the Ethiopian malaria epidemic-prone setting: an ethnobotanical survey.

    PubMed

    Karunamoorthi, Kaliyaperumal; Hailu, Teklu

    2014-02-12

    The usage of insect repellent plants (IRPs) is one of the centuries-old practices in Africa. In Ethiopia, malaria remains a leading cause of morbidity and mortality, subsequently the majority of people have a tendency to apply various plants as repellents to reduce or interrupt the biting activity of insects. Accordingly, this survey was undertaken to document and evaluate knowledge and usage practices of the local inhabitants on IRPs in the malaria epidemic-prone setting of Ethiopia. Ethnobotanical survey was conducted between January and May 2013. Selected 309 household members were interviewed by administering pre-tested questionnaire on knowledge and usage practices of repellent plants, in Bechobore Kebele, Jimma Zone, Ethiopia. Overall, 70.2% (217/309) and 91.8% (199/217) of the respondents have had ample awareness and usage practices of repellent plants, respectively. Informants cited about twenty-two plant species as repellents and also indicated that these plants are useful(85.5%), accessible(86.8%), and affordable(83.9%) too. Residents mainly applying dried leaves [93.9% (187/199)] by means of burning/smouldering [98.9% (197/199)] with the traditional charcoal stove to repel insects, primarily mosquitoes. About 52.8% (105/199) of the informants using approximately 15g of dried plant-materials every day. A Chi-square analysis shows statistically a significant link between the knowledge on repellent plants and gender as well as average monthly income although not with the age of the respondents. Nevertheless, the repellent plant usage custom was not significantly associated with gender, monthly income, and age of the informants. Though most of the people have had an adequate awareness still a sizable faction of society suffers with deprivation of IRPs knowledge and usage practices. Therefore, this study calls for more surveys to conserve the existing indigenous knowledge and cultural practices. It could lay the first stone to develop the next generation cost-effective vector control tools in the near future.

  20. Five Year Results of US Intergroup/RTOG 9704 With Postoperative CA 19-9 {<=}90 U/mL and Comparison to the CONKO-001 Trial

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

    Berger, Adam C., E-mail: adam.berger@jefferson.edu; Winter, Kathryn; Hoffman, John P.

    2012-11-01

    Purpose: Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of {<=}90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. Methods and Materials: CA 19-9 expression was analyzed as a dichotomized variable ({<=}90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. Results: Both univariate (hazardmore » ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of {>=}90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 {>=}90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. Conclusions: This analysis demonstrates that patients with postresection CA 19-9 values {>=}90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).« less

  1. Developmental Decline in the MicroRNA 199a (miR-199a)/miR-214 Cluster in Human Fetal Lung Promotes Type II Cell Differentiation by Upregulating Key Transcription Factors.

    PubMed

    Mishra, Ritu; Benlhabib, Houda; Guo, Wei; Lerma Cervantes, Connie B; Mendelson, Carole R

    2018-06-01

    The major surfactant protein, SP-A (a product of the SFTPA gene), serves as a marker of type II pneumocyte differentiation and surfactant synthesis. SFTPA expression in cultured human fetal lung (HFL) epithelial cells is upregulated by hormones that increase cyclic AMP (cAMP) and activate TTF-1/NKX2.1 and NF-κB. To further define mechanisms for type II cell differentiation and induction of SP-A, we investigated roles of microRNAs (miRNAs). Using microarray to identify differentially expressed miRNAs in HFL epithelial cells during type II cell differentiation in culture, we observed that members of the miRNA 199a (miR-199a)/miR-214 cluster were significantly downregulated during differentiation. Validated and predicted targets of miR-199a-3p/miR-199a-5p and miR-214, which serve roles in type II cell differentiation (COX-2, NF-κB p50/p65, and CREB1), and the CREB1 target, C/EBPβ, were coordinately upregulated. Accordingly, overexpression of miR-199a-5p, miR-199a-3p, or miR-214 mimics in cultured HFL epithelial cells decreased COX-2, NF-κB p50/p65, CREB1, and C/EBPβ proteins, with an associated inhibition of SP-A expression. Interestingly, overexpression of the EMT factor, ZEB1, which declines during cAMP-induced type II cell differentiation, increased pri-miR-199a and reduced the expression of the targets NF-κB/p50 and COX-2. Collectively, these findings suggest that the developmental decline in miR-199a/miR-214 in HFL causes increased expression of critical targets that enhance type II cell differentiation and SP-A expression. Copyright © 2018 American Society for Microbiology.

  2. Unraveling the Deleterious Effects of Cancer-Driven STK11 Mutants Through Conformational Sampling Approach.

    PubMed

    Lopus, Merlin; Paul, D Meshach; Rajasekaran, R

    2016-01-01

    Tumor suppressor gene, STK11, encodes for serine-threonine kinase, which has a critical role in regulating cell growth and apoptosis. Mutations of the same lead to the inactivation of STK11, which eventually causes different types of cancer. In this study, we focused on identifying those driver mutations through analyzing structural variations of mutants, viz., D194N, E199K, L160P, and Y49D. Native and the mutants were analyzed to determine their geometrical deviations such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, potential energy, and solvent-accessible surface area using conformational sampling technique. Additionally, the global minimized structure of native and mutants was further analyzed to compute their intramolecular interactions and distribution of secondary structure. Subsequently, simulated thermal denaturation and docking studies were performed to determine their structural variations, which in turn alter the formation of active complex that comprises STK11, STRAD, and MO25. The deleterious effect of the mutants would result in a comparative loss of enzyme function due to variations in their binding energy pertaining to spatial conformation and flexibility. Hence, the structural variations in binding energy exhibited by the mutants, viz., D194N, E199K, L160P, and Y49D, to that of the native, consequently lead to pathogenesis.

  3. 7 CFR 205.106-205.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false [Reserved] 205.106-205.199 Section 205.106-205.199 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE (CONTINUED) ORGANIC FOODS PRODUCTION ACT...

  4. 7 CFR 1755.99-1755.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false [Reserved] 1755.99-1755.199 Section 1755.99-1755.199 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE TELECOMMUNICATIONS POLICIES ON SPECIFICATIONS, ACCEPTABLE MATERIALS, AND STANDARD CONTRACT FORMS...

  5. Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma?

    PubMed

    Wang, Jun-Ke; Hu, Hai-Jie; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Liu, Fei; Cheng, Nan-Sheng; Li, Fu-Yu

    2017-07-11

    To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216-9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391-28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107-14.459; P = 0.034). Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.

  6. 46 CFR 199.170 - Line-throwing appliance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Line-throwing appliance. 199.170 Section 199.170 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS... appliance. (a) General. Each vessel must have a line-throwing appliance approved under approval series 160...

  7. 46 CFR 199.01 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Purpose. 199.01 Section 199.01 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR... appliances and arrangements for all inspected U.S. vessels except for— (1) Offshore supply vessels, which are...

  8. 46 CFR 199.600 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false General. 199.600 Section 199.600 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR.... This subpart sets out specific exemptions and alternatives to requirements in subparts A, B, C, D, and...

  9. [An attempt for standardization of serum CA19-9 levels, in order to dissolve the gap between three different methods].

    PubMed

    Hayashi, Kuniki; Hoshino, Tadashi; Yanai, Mitsuru; Tsuchiya, Tatsuyuki; Kumasaka, Kazunari; Kawano, Kinya

    2004-06-01

    It is well known that serious method-related differences exist in results of serum CA19-9, and the necessity of standardization has been pointed out. In this study, differences of serum tumor marker CA19-9 levels obtained by various immunoassay kits (CLEIA, FEIA, LPIA and RIA) were evaluated in sixty-seven clinical samples and five calibrators and the possibility to improve the inter-methodological differences were observed not only for clinical samples but also for calibrators. We supposed an assumed standard material using by a calibrator. We calculated the serum levels of CA19-9 when using the assumed standard material for three different measurement methods. We approximate the CA19-9 values using by this method. It is suggested that the obtained CA19-9 values could be approximated by recalculation with the assumed standard material would be able to correct between-method and between-laboratory discrepancies in particular systematic errors.

  10. High efficacy of the BCL-2 inhibitor ABT199 (venetoclax) in BCL-2 high-expressing neuroblastoma cell lines and xenografts and rational for combination with MCL-1 inhibition

    PubMed Central

    Bate-Eya, Laurel T.; den Hartog, Ilona J.M.; van der Ploeg, Ida; Schild, Linda; Koster, Jan; Santo, Evan E.; Westerhout, Ellen M.; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.; Dolman, M. Emmy M.

    2016-01-01

    The anti-apoptotic protein B cell lymphoma/leukaemia 2 (BCL-2) is highly expressed in neuroblastoma and plays an important role in oncogenesis. In this study, the selective BCL-2 inhibitor ABT199 was tested in a panel of neuroblastoma cell lines with diverse expression levels of BCL-2 and other BCL-2 family proteins. ABT199 caused apoptosis more potently in neuroblastoma cell lines expressing high BCL-2 and BIM/BCL-2 complex levels than low expressing cell lines. Effects on cell viability correlated with effects on BIM displacement from BCL-2 and cytochrome c release from the mitochondria. ABT199 treatment of mice with neuroblastoma tumors expressing high BCL-2 levels only resulted in growth inhibition, despite maximum BIM displacement from BCL-2 and the induction of a strong apoptotic response. We showed that neuroblastoma cells might survive ABT199 treatment due to its acute upregulation of the anti-apoptotic BCL-2 family protein myeloid cell leukaemia sequence 1 (MCL-1) and BIM sequestration by MCL-1. In vitro inhibition of MCL-1 sensitized neuroblastoma cell lines to ABT199, confirming the pivotal role of MCL-1 in ABT199 resistance. Our findings suggest that neuroblastoma patients with high BCL-2 and BIM/BCL-2 complex levels might benefit from combination treatment with ABT199 and compounds that inhibit MCL-1 expression. PMID:27056887

  11. Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma.

    PubMed

    Chiron, David; Dousset, Christelle; Brosseau, Carole; Touzeau, Cyrille; Maïga, Sophie; Moreau, Philippe; Pellat-Deceunynck, Catherine; Le Gouill, Steven; Amiot, Martine

    2015-04-20

    The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD50 < 10 nM). Mcl-1 and Bcl-xL both confer resistance to ABT-199-specific killing and BCL2/(BCLXL+MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-x(L) up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors.

  12. Expression of Glucose-Regulated Protein 78 and miR-199a in Rat Brain After Fatal Ligature Strangulation.

    PubMed

    Feng, Xueying; Zhang, Dongchuan; Gong, Qingjin; Zhang, Zhiyong; Quan, Li

    2017-03-01

    The roles of endoplasmic reticulum (ER) stress and microRNA in the brain tissue after fatal mechanical asphyxia have not been clearly elucidated. We examined the expression of glucose-regulated protein 78 (GRP78), the key regulator of unfolded protein response, and miR-199a in the brain tissues of rats subjected to fatal ligature strangulation to understand the roles of ER stress and microRNA in ligature strangulation. The expressions of GRP78 and miR-199a in rat cortex, hippocampi, and midbrain were measured by immunohistochemistry and Western blot analysis in a rat model of ligature strangulation. Furthermore, the levels of miR-199a-3p and miR-199a-5p were detected by real-time fluorescent quantitative polymerase chain reaction. Glucose-regulated protein 78 was highly expressed in the cortex and midbrain in the ligature strangulation group (P < 0.01) when compared with the control group. The expression of GRP78 in the hippocampi showed no significant difference between the 2 groups. miR-199a-3p in the cortex and midbrain was significantly down-regulated in the ligature strangulation group (P < 0.01). However, miR-199a-5p in each brain region showed no significant difference between the 2 groups. In conclusion, ER stress was involved in the physiological and pathological processes of ligature strangulation. Furthermore, upstream miR-199a may play an important regulatory role in mechanical asphyxia.

  13. Radiopharmaceuticals for SPECT cancer detection

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

    Chernov, V. I., E-mail: chernov@oncology.tomsk.ru; Medvedeva, A. A., E-mail: tickayaAA@oncology.tomsk.ru; Zelchan, R. V., E-mail: r.zelchan@yandex.ru

    2016-08-02

    The purpose of the study was to assess the efficacy of single photon emission computed tomography (SPECT) with {sup 199}Tl and {sup 99}mTc-MIBI in the detection of breast, laryngeal and hypopharyngeal cancers. A total of 220 patients were included into the study: 120 patients with breast lesions (100 patients with breast cancer and 20 patients with benign breast tumors) and 100 patients with laryngeal/hypopharyngeal diseases (80 patients with laryngeal/hypopharyngeal cancer and 20 patients with benign laryngeal/hypopharyngeal lesions). No abnormal {sup 199}Tl uptake was seen in all patients with benign breast and laryngeal lesions, indicating a 100% specificity of {sup 199}Tlmore » SPECT. In the breast cancer patients, the increased {sup 199}Tl uptake in the breast was visualized in 94.8% patients, {sup 99m}Tc-MIBI—in 93.4% patients. The increased {sup 199}Tl uptake in axillary lymph nodes was detected in 60% patients, and {sup 99m}Tc-MIBI—in 93.1% patients. In patients with laryngeal/hypopharyngeal cancer, the sensitivity of SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI was 95%. The {sup 199}Tl SPECT sensitivity in identification of regional lymph node metastases in the patients with laryngeal/hypopharyngeal cancer was 75% and the {sup 99m}Tc-MIBI SPECT sensitivity was 17%. The data obtained showed that SPECT with {sup 199}Tl and {sup 99m}Tc-MIBI can be used as one of the additional imaging methods in detection of tumors.« less

  14. 38 CFR 19.9 - Remand for further development.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Remand for further development. 19.9 Section 19.9 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....9 Remand for further development. (a) General. If further evidence, clarification of the evidence...

  15. 46 CFR 199.500 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false General. 199.500 Section 199.500 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES AND ARRANGEMENTS LIFESAVING SYSTEMS FOR... subpart sets out requirements in addition to the requirements in subparts A, B, C, and D of this part...

  16. 49 CFR 199.101 - Anti-drug plan.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing...; (2) The name and address of each laboratory that analyzes the specimens collected for drug testing... 49 Transportation 3 2014-10-01 2014-10-01 false Anti-drug plan. 199.101 Section 199.101...

  17. 49 CFR 199.101 - Anti-drug plan.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing...; (2) The name and address of each laboratory that analyzes the specimens collected for drug testing... 49 Transportation 3 2013-10-01 2013-10-01 false Anti-drug plan. 199.101 Section 199.101...

  18. 78 FR 63568 - Proposed Collection; Comment Request for Rev. Proc. 2007-35

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... Revenue Procedure 2007-35, Statistical Sampling for purposes of Section 199. DATES: Written comments... . SUPPLEMENTARY INFORMATION: Title: Statistical Sampling for purposes of Section 199. OMB Number: 1545-2072... statistical sampling may be used in purposes of section 199, which provides a deduction for income...

  19. 46 CFR 199.201 - Survival craft.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft. 199.201 Section 199.201 Shipping COAST... craft. (a) Each survival craft must be approved and equipped as follows: (1) Each lifeboat must be... addition to the survival craft required in paragraph (b)(1) of this section, additional liferafts must be...

  20. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required by...

  1. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required by...

  2. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required by...

  3. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required by...

  4. 49 CFR 199.229 - Reporting of alcohol testing results.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Reporting of alcohol testing results. 199.229... ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.229 Reporting of alcohol testing results. (a) Each... alcohol testing results using the Management Information System (MIS) form and instructions as required by...

  5. 7 CFR 800.199 - Conflict-of-interest provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Conflict-of-interest provisions. 800.199 Section 800... Delegations, Designations, Approvals, Contracts, and Conflicts of Interest § 800.199 Conflict-of-interest...) Prohibited conflicts of interest. Unless waived on a case-by-case basis by the Administrator under section 11...

  6. 46 CFR 199.214 - Immersion suits and thermal protective aids.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Immersion suits and thermal protective aids. 199.214... Passenger Vessels § 199.214 Immersion suits and thermal protective aids. (a) Each passenger vessel must... an immersion suit. (c) The immersion suits and thermal protective aids required under paragraphs (a...

  7. 46 CFR 199.214 - Immersion suits and thermal protective aids.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Immersion suits and thermal protective aids. 199.214... Passenger Vessels § 199.214 Immersion suits and thermal protective aids. (a) Each passenger vessel must... an immersion suit. (c) The immersion suits and thermal protective aids required under paragraphs (a...

  8. 46 CFR 199.214 - Immersion suits and thermal protective aids.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Immersion suits and thermal protective aids. 199.214... Passenger Vessels § 199.214 Immersion suits and thermal protective aids. (a) Each passenger vessel must... an immersion suit. (c) The immersion suits and thermal protective aids required under paragraphs (a...

  9. 46 CFR 199.214 - Immersion suits and thermal protective aids.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Immersion suits and thermal protective aids. 199.214... Passenger Vessels § 199.214 Immersion suits and thermal protective aids. (a) Each passenger vessel must... an immersion suit. (c) The immersion suits and thermal protective aids required under paragraphs (a...

  10. 32 CFR 199.18 - Uniform HMO Benefit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Uniform HMO Benefit. 199.18 Section 199.18... Benefit. (a) In general. There is established a Uniform HMO Benefit. The purpose of the Uniform HMO benefit is to establish a health benefit option modeled on health maintenance organization plans. This...

  11. 49 CFR 192.199 - Requirements for design of pressure relief and limiting devices.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Requirements for design of pressure relief and limiting devices. 192.199 Section 192.199 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL...

  12. 49 CFR 192.199 - Requirements for design of pressure relief and limiting devices.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Requirements for design of pressure relief and limiting devices. 192.199 Section 192.199 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL...

  13. 46 CFR 199.100 - Manning of survival craft and supervision.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Manning of survival craft and supervision. 199.100 Section 199.100 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES....100 Manning of survival craft and supervision. (a) There must be a sufficient number of trained...

  14. 46 CFR 199.100 - Manning of survival craft and supervision.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Manning of survival craft and supervision. 199.100 Section 199.100 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES....100 Manning of survival craft and supervision. (a) There must be a sufficient number of trained...

  15. 46 CFR 199.100 - Manning of survival craft and supervision.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Manning of survival craft and supervision. 199.100 Section 199.100 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES....100 Manning of survival craft and supervision. (a) There must be a sufficient number of trained...

  16. 46 CFR 199.100 - Manning of survival craft and supervision.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Manning of survival craft and supervision. 199.100 Section 199.100 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LIFESAVING APPLIANCES....100 Manning of survival craft and supervision. (a) There must be a sufficient number of trained...

  17. 49 CFR 199.119 - Reporting of anti-drug testing results.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Reporting of anti-drug testing results. 199.119... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.119 Reporting of anti-drug testing results. (a) Each large operator...

  18. 49 CFR 199.119 - Reporting of anti-drug testing results.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Reporting of anti-drug testing results. 199.119... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.119 Reporting of anti-drug testing results. (a) Each large operator...

  19. 49 CFR 199.109 - Review of drug testing results.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Review of drug testing results. 199.109 Section... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.109 Review of drug testing results. (a) MRO appointment. Each operator shall...

  20. 49 CFR 199.109 - Review of drug testing results.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Review of drug testing results. 199.109 Section... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.109 Review of drug testing results. (a) MRO appointment. Each operator shall...

  1. 49 CFR 199.109 - Review of drug testing results.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Review of drug testing results. 199.109 Section... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.109 Review of drug testing results. (a) MRO appointment. Each operator shall...

  2. 49 CFR 199.109 - Review of drug testing results.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Review of drug testing results. 199.109 Section... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.109 Review of drug testing results. (a) MRO appointment. Each operator shall...

  3. 49 CFR 199.119 - Reporting of anti-drug testing results.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Reporting of anti-drug testing results. 199.119... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.119 Reporting of anti-drug testing results. (a) Each large operator...

  4. 49 CFR 199.119 - Reporting of anti-drug testing results.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Reporting of anti-drug testing results. 199.119... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.119 Reporting of anti-drug testing results. (a) Each large operator...

  5. 49 CFR 199.109 - Review of drug testing results.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Review of drug testing results. 199.109 Section... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.109 Review of drug testing results. (a) MRO appointment. Each operator shall...

  6. 49 CFR 199.119 - Reporting of anti-drug testing results.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Reporting of anti-drug testing results. 199.119... HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.119 Reporting of anti-drug testing results. (a) Each large operator...

  7. 46 CFR 199.214 - Immersion suits and thermal protective aids.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Immersion suits and thermal protective aids. 199.214... Passenger Vessels § 199.214 Immersion suits and thermal protective aids. (a) Each passenger vessel must... an immersion suit. (c) The immersion suits and thermal protective aids required under paragraphs (a...

  8. 9 CFR 381.199 - Inspection of poultry products offered for entry.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND VOLUNTARY INSPECTION AND CERTIFICATION POULTRY PRODUCTS INSPECTION REGULATIONS Imported Poultry... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Inspection of poultry products offered for entry. 381.199 Section 381.199 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE...

  9. 46 CFR 199.178 - Marking of stowage locations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Marking of stowage locations. 199.178 Section 199.178... locations. (a) Containers, brackets, racks, and other similar stowage locations for lifesaving equipment... that location. (b) If more than one device is stowed in a location, the number of devices stowed must...

  10. 32 CFR 199.7 - Claims submission, review, and payment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Claims submission, review, and payment. 199.7 Section 199.7 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE... patient's treatment and progress. Accurate and timely completion of orders, notes, etc., enable different...

  11. A simple architecture with self-assembled monolayers to build immunosensors for detecting the pancreatic cancer biomarker CA19-9.

    PubMed

    Soares, Andrey Coatrini; Soares, Juliana Coatrini; Shimizu, Flavio Makoto; Rodrigues, Valquiria da Cruz; Awan, Iram Taj; Melendez, Matias Eliseo; Piazzetta, Maria Helena Oliveira; Gobbi, Angelo Luiz; Reis, Rui Manuel; Fregnani, José Humberto T G; Carvalho, André Lopes; Oliveira, Osvaldo N

    2018-05-14

    The challenge of the early diagnosis of pancreatic cancer in routine clinical practice requires low-cost means of detection, and this may be achieved with immunosensors based on electrical or electrochemical principles. In this paper, we report a potentially low-cost immunosensor built with interdigitated gold electrodes coated with a self-assembled monolayer and a layer of anti-CA19-9 antibodies, which is capable of detecting the pancreatic cancer biomarker CA19-9 using electrical impedance spectroscopy. Due to specific, irreversible adsorption of CA19-9 onto its corresponding antibody, according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), the immunosensor is highly sensitive and selective. It could detect CA19-9 in commercial samples with a limit of detection of 0.68 U mL-1, in addition to distinguishing between blood serum samples from patients with different concentrations of CA19-9. Furthermore, by treating the capacitance data with information visualization methods, we were able to verify the selectivity and robustness of the immunosensor with regard to false positives, as the samples containing higher CA19-9 concentrations, including those from tumor cells, could be distinguished from those with possible interferents.

  12. Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

    PubMed Central

    Schultz, Nicolai A.; Christensen, Ib J.; Werner, Jens; Giese, Nathalia; Jensen, Benny V.; Larsen, Ole; Bjerregaard, Jon K.; Pfeiffer, Per; Calatayud, Dan; Nielsen, Svend E.; Yilmaz, Mette K.; Holländer, Niels H.; Wøjdemann, Morten; Bojesen, Stig E.; Nielsen, Kaspar R.; Johansen, Julia S.

    2013-01-01

    Purpose We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival. Patients and Methods In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay. Results Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months). Conclusions Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis. PMID:23840582

  13. miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1

    PubMed Central

    Courcot, Elisabeth; Roderburg, Christoph; Cauffiez, Christelle; Aubert, Sébastien; Copin, Marie-Christine; Wallaert, Benoit; Glowacki, François; Dewaeles, Edmone; Milosevic, Jadranka; Maurizio, Julien; Tedrow, John; Marcet, Brice; Lo-Guidice, Jean-Marc; Kaminski, Naftali; Barbry, Pascal; Luedde, Tom; Perrais, Michael

    2013-01-01

    As miRNAs are associated with normal cellular processes, deregulation of miRNAs is thought to play a causative role in many complex diseases. Nevertheless, the precise contribution of miRNAs in fibrotic lung diseases, especially the idiopathic form (IPF), remains poorly understood. Given the poor response rate of IPF patients to current therapy, new insights into the pathogenic mechanisms controlling lung fibroblasts activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. To identify miRNAs with potential roles in lung fibrogenesis, we performed a genome-wide assessment of miRNA expression in lungs from two different mouse strains known for their distinct susceptibility to develop lung fibrosis after bleomycin exposure. This led to the identification of miR-199a-5p as the best miRNA candidate associated with bleomycin response. Importantly, miR-199a-5p pulmonary expression was also significantly increased in IPF patients (94 IPF versus 83 controls). In particular, levels of miR-199a-5p were selectively increased in myofibroblasts from injured mouse lungs and fibroblastic foci, a histologic feature associated with IPF. Therefore, miR-199a-5p profibrotic effects were further investigated in cultured lung fibroblasts: miR-199a-5p expression was induced upon TGFβ exposure, and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts including proliferation, migration, invasion, and differentiation into myofibroblasts. In addition, we demonstrated that miR-199a-5p is a key effector of TGFβ signaling in lung fibroblasts by regulating CAV1, a critical mediator of pulmonary fibrosis. Remarkably, aberrant expression of miR-199a-5p was also found in unilateral ureteral obstruction mouse model of kidney fibrosis, as well as in both bile duct ligation and CCl4-induced mouse models of liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. MiR-199a-5p thus behaves as a major regulator of tissue fibrosis with therapeutic potency to treat fibroproliferative diseases. PMID:23459460

  14. 49 CFR 199.231 - Access to facilities and records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Access to facilities and records. 199.231 Section... TESTING Alcohol Misuse Prevention Program § 199.231 Access to facilities and records. (a) Except as... access to all facilities utilized in complying with the requirements of this subpart to the Secretary of...

  15. 46 CFR 199.130 - Stowage of survival craft.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Stowage of survival craft. 199.130 Section 199.130... craft. (a) General. Each survival craft must be stowed— (1) As close to the accommodation and service spaces as possible; (2) So that neither the survival craft nor its stowage arrangements will interfere...

  16. 26 CFR 1.199-7 - Expanded affiliated groups.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... in § 1.199-3(h)), a qualified film (as defined in § 1.199-3(k)), or electricity, natural gas, or... disposing member disposes of the QPP, qualified film, or utilities, then the disposing member is treated as... QPP, qualified film, or utilities in determining whether its gross receipts are domestic production...

  17. 10 CFR 205.199F - Ex parte communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... communications include any ex parte oral or written communications relative to the merits of a Proposed Remedial... public and serve a copy of a written communication or a memorandum summarizing an oral communication to... 10 Energy 3 2010-01-01 2010-01-01 false Ex parte communications. 205.199F Section 205.199F Energy...

  18. 12 CFR 19.9 - Ex parte communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... parte communication means any material oral or written communication relevant to the merits of an... communication is oral, a memorandum stating the substance of the communication) to be placed on the record of... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Ex parte communications. 19.9 Section 19.9...

  19. 49 CFR 199.111 - Retention of samples and additional testing.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.111 Retention of samples and additional testing. (a... other than the unauthorized use of a prohibited drug, and if timely additional testing is requested by... 49 Transportation 3 2011-10-01 2011-10-01 false Retention of samples and additional testing. 199...

  20. 49 CFR 199.111 - Retention of samples and additional testing.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.111 Retention of samples and additional testing. (a... other than the unauthorized use of a prohibited drug, and if timely additional testing is requested by... 49 Transportation 3 2013-10-01 2013-10-01 false Retention of samples and additional testing. 199...

  1. 49 CFR 199.111 - Retention of samples and additional testing.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.111 Retention of samples and additional testing. (a... other than the unauthorized use of a prohibited drug, and if timely additional testing is requested by... 49 Transportation 3 2012-10-01 2012-10-01 false Retention of samples and additional testing. 199...

  2. 49 CFR 199.111 - Retention of samples and additional testing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.111 Retention of samples and additional testing. (a... other than the unauthorized use of a prohibited drug, and if timely additional testing is requested by... 49 Transportation 3 2010-10-01 2010-10-01 false Retention of samples and additional testing. 199...

  3. 49 CFR 199.111 - Retention of samples and additional testing.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.111 Retention of samples and additional testing. (a... other than the unauthorized use of a prohibited drug, and if timely additional testing is requested by... 49 Transportation 3 2014-10-01 2014-10-01 false Retention of samples and additional testing. 199...

  4. miR-199a-3p regulates brown adipocyte differentiation through mTOR signaling pathway.

    PubMed

    Gao, Yao; Cao, Yan; Cui, Xianwei; Wang, Xingyun; Zhou, Yahui; Huang, Fangyan; Wang, Xing; Wen, Juan; Xie, Kaipeng; Xu, Pengfei; Guo, Xirong; You, Lianghui; Ji, Chenbo

    2018-05-10

    Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans. Conversely, its level was induced during the differentiation course of human white pre-adipocytes derived from visceral fat. miR-199a-3p expression was relatively abundant in interscapular BAT (iBAT) and differentially regulated in the activated and aging BAT in mice. Additionally, miR-199a-3p expression level in human brown adipocytes was observed decreased upon thermogenic activation and increased by aging-related stimuli. Using primary pre-adipocytes, miR-199a-3p over-expression was capable of attenuating lipid accumulation and adipogenic gene expression as well as impairing brown adipocytes' metabolic characteristics as revealed by decreased mitochondrial DNA content and respiration. Suppression of miR-199a-3p by a locked nucleic acid (LNA) modified-anti-miR led to increased differentiation and thermogenesis in human brown adipocytes. By combining target prediction and examination, we identified mechanistic target of rapamycin kinase (mTOR) as a direct target of miR-199a-3p that affected brown adipogenesis and thermogenesis. Our results point to a novel role for miR-199a-3p and its downstream effector mTOR in human brown adipocyte differentiation and maintenance of thermogenic characteristics, which can be manipulated as therapeutic targets against obesity and its related metabolic disorders. Copyright © 2018. Published by Elsevier B.V.

  5. The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1α prolyl hydroxylation by regulating cellular iron levels.

    PubMed

    Miles, Anna L; Burr, Stephen P; Grice, Guinevere L; Nathan, James A

    2017-03-15

    Hypoxia Inducible transcription Factors (HIFs) are principally regulated by the 2-oxoglutarate and Iron(II) prolyl hydroxylase (PHD) enzymes, which hydroxylate the HIFα subunit, facilitating its proteasome-mediated degradation. Observations that HIFα hydroxylation can be impaired even when oxygen is sufficient emphasise the importance of understanding the complex nature of PHD regulation. Here, we use an unbiased genome-wide genetic screen in near-haploid human cells to uncover cellular processes that regulate HIF1α. We identify that genetic disruption of the Vacuolar H+ ATPase (V-ATPase), the key proton pump for endo-lysosomal acidification, and two previously uncharacterised V-ATPase assembly factors, TMEM199 and CCDC115, stabilise HIF1α in aerobic conditions. Rather than preventing the lysosomal degradation of HIF1α, disrupting the V-ATPase results in intracellular iron depletion, thereby impairing PHD activity and leading to HIF activation. Iron supplementation directly restores PHD catalytic activity following V-ATPase inhibition, revealing important links between the V-ATPase, iron metabolism and HIFs.

  6. Comparison of Quinn's Advantage fertilization medium and tissue culture medium 199 for in vitro maturation of oocytes.

    PubMed

    Lin, Yu-Hung; Hwang, Jiann-Loung; Huang, Lee-Wen; Seow, Kok-Min; Hsieh, Bih-Chwen; Tzeng, Chii-Ruey

    2014-03-01

    The purpose of the study was to compare the Quinn's Advantage fertilization medium (Q1) and the tissue culture medium 199 (TCM199) for in vitro maturation (IVM) of oocytes and ammonium production during IVM. The immature murine oocytes were randomly added into Q1 and TCM199. Ammonium concentrations were measured at the start and after 18 hours of IVM, and the mature oocytes were fertilized and cultured into blastocysts. The blastocysts were then stained for inner cell mass (ICM) and trophectoderm. The maturation rate was higher in Q1 than in TCM199 (85.7% vs. 76.6%, p = 0.024). The fertilization and blastocyst rates were slightly higher in Q1, but not significant. Differential staining of the blastocysts showed slightly higher ICM ratio in the blastocysts derived from Q1. Mean ammonium concentrations in Q1 and TCM199 at Time 0 were 184.9 and 339.2 μg/dL, respectively (p = 0.05), and after 18 hours of IVM were 268.7 and 443.6 μg/dL, respectively (p = 0.045). Addition of ammonium chloride into Q1 adversely affects IVM. Q1 is superior to TCM199 in terms of oocyte maturation, which may be due to lower ammonium concentration. Copyright © 2014. Published by Elsevier B.V.

  7. Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel

    PubMed Central

    Namkung, Junghyun; Yi, Sung Gon; Kim, Hyunsoo; Yu, Jiyoung; Kim, Yongkang; Kwon, Min-Seok; Kwon, Wooil; Oh, Do-Youn; Kim, Sun-Whe; Jeong, Seung-Yong; Han, Wonshik; Lee, Kyu Eun; Heo, Jin Seok; Park, Joon Oh; Park, Joo Kyung; Kim, Song Cheol; Kang, Chang Moo; Lee, Woo Jin; Lee, Seungyeoun; Han, Sangjo; Park, Taesung; Jang, Jin-Young; Kim, Youngsoo

    2017-01-01

    Due to its high mortality rate and asymptomatic nature, early detection rates of pancreatic ductal adenocarcinoma (PDAC) remain poor. We measured 1000 biomarker candidates in 134 clinical plasma samples by multiple reaction monitoring-mass spectrometry (MRM-MS). Differentially abundant proteins were assembled into a multimarker panel from a training set (n=684) and validated in independent set (n=318) from five centers. The level of panel proteins was also confirmed by immunoassays. The panel including leucine-rich alpha-2 glycoprotein (LRG1), transthyretin (TTR), and CA19-9 had a sensitivity of 82.5% and a specificity of 92.1%. The triple-marker panel exceeded the diagnostic performance of CA19-9 by more than 10% (AUCCA19-9 = 0.826, AUCpanel= 0.931, P < 0.01) in all PDAC samples and by more than 30% (AUCCA19-9 = 0.520, AUCpanel = 0.830, P < 0.001) in patients with normal range of CA19-9 (<37U/mL). Further, it differentiated PDAC from benign pancreatic disease (AUCCA19-9 = 0.812, AUCpanel = 0.892, P < 0.01) and other cancers (AUCCA19-9 = 0.796, AUCpanel = 0.899, P < 0.001). Overall, the multimarker panel that we have developed and validated in large-scale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC. PMID:29190982

  8. A low-toxic site-directed mutant of Clostridium perfringens ε-toxin as a potential candidate vaccine against enterotoxemia.

    PubMed

    Li, Qing; Xin, Wenwen; Gao, Shan; Kang, Lin; Wang, Jinglin

    2013-11-01

    Clostridium perfringens epsilon toxin (ETX), one of the most potent toxins known, is a potential biological weapon; therefore, the development of an effective vaccine is important for preventing intoxication or disease by ETX. In this study, genetically detoxified epsilon toxin mutants were developed as candidate vaccines. We used site-directed mutagenesis to mutate the essential amino acid residues (His106, Ser111 and Phe199). Six site-directed mutants of ETX (mETX (H106P) , mETX (S111H) , mETX (S111Y) , mETX (F199H) , mETX (F199E) , mETX (S111YF199E) ) were generated and then expressed in Escherichia coli. Both mETX (F199E) and mETX (H106P) with low or non-cytotoxicity that retained their immunogenicity were selected to immunize mice 3 times, and the mouse survival data were recorded after challenging with recombinant wild-type ETX. mETX (F199E) induces the same protection as mETX (H106P) , which was reported previously as a promising toxin mutant for vaccine, and both of them could protect immunized mice against a 100× LD₅₀ dose of active wild-type recombinant ETX. This work showed that mETX (F199E) is another promising candidate vaccine against enterotoxemia and other diseases caused by ETX.

  9. Streptococcus suis DivIVA Protein Is a Substrate of Ser/Thr Kinase STK and Involved in Cell Division Regulation

    PubMed Central

    Ni, Hua; Fan, Weiwei; Li, Chaolong; Wu, Qianqian; Hou, Hongfen; Hu, Dan; Zheng, Feng; Zhu, Xuhui; Wang, Changjun; Cao, Xiangrong; Shao, Zhu-Qing; Pan, Xiuzhen

    2018-01-01

    Streptococcus suis serotype 2 is an important swine pathogen and an emerging zoonotic agent that causes severe infections. Recent studies have reported a eukaryotic-like Ser/Thr protein kinase (STK) gene and characterized its role in the growth and virulence of different S. suis 2 strains. In the present study, phosphoproteomic analysis was adopted to identify substrates of the STK protein. Seven proteins that were annotated to participate in different cell processes were identified as potential substrates, which suggests the pleiotropic effects of stk on S. suis 2 by targeting multiple pathways. Among them, a protein characterized as cell division initiation protein (DivIVA) was further investigated. In vitro analysis demonstrated that the recombinant STK protein directly phosphorylates threonine at amino acid position 199 (Thr-199) of DivIVA. This effect could be completely abolished by the T199A mutation. To determine the specific role of DivIVA in growth and division, a divIVA mutant was constructed. The ΔdivIVA strain exhibited impaired growth and division, including lower viability, enlarged cell mass, asymmetrical division caused by aberrant septum, and extremely weak pathogenicity in a mouse infection model. Collectively, our results reveal that STK regulates the cell growth and virulence of S. suis 2 by targeting substrates that are involved in different biological pathways. The inactivation of DivIVA leads to severe defects in cell division and strongly attenuates pathogenicity, thereby indicating its potential as a molecular drug target against S. suis. PMID:29616196

  10. 15 CFR 19.9 - When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial Management Service for collection? 19.9 Section 19.9 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To...

  11. 15 CFR 19.9 - When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial Management Service for collection? 19.9 Section 19.9 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To...

  12. 15 CFR 19.9 - When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial Management Service for collection? 19.9 Section 19.9 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To...

  13. 15 CFR 19.9 - When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial Management Service for collection? 19.9 Section 19.9 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To...

  14. 15 CFR 19.9 - When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false When will Commerce entities transfer a Commerce debt to the Treasury Department's Financial Management Service for collection? 19.9 Section 19.9 Commerce and Foreign Trade Office of the Secretary of Commerce COMMERCE DEBT COLLECTION Procedures To...

  15. 32 CFR 199.5 - TRICARE Extended Care Health Option (ECHO).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-eligible dependents: (i) A spouse, child, or unmarried person (as described in § 199.3(b)(2)(i), (b)(2)(ii.... (ii) An abused dependent as described in § 199.3(b)(2)(iii). (iii) A spouse, child, or unmarried... member for over one-half of such dependent's support. (iv) A spouse, child, or unmarried person (as...

  16. 46 CFR 199.03 - Relationship to international standards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... supplemented by a Record of Equipment, or a valid Cargo Ship Safety Equipment Certificate supplemented by a... lifejackets, if carried, must be of the same or similar design as required by § 199.70(b). (5) Containers for... appliance in accordance with § 199.170(c)(2). (13) Immersion suits must be carried on all cargo vessels...

  17. 46 CFR 199.03 - Relationship to international standards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... supplemented by a Record of Equipment, or a valid Cargo Ship Safety Equipment Certificate supplemented by a... lifejackets, if carried, must be of the same or similar design as required by § 199.70(b). (5) Containers for... appliance in accordance with § 199.170(c)(2). (13) Immersion suits must be carried on all cargo vessels...

  18. 46 CFR 199.03 - Relationship to international standards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... supplemented by a Record of Equipment, or a valid Cargo Ship Safety Equipment Certificate supplemented by a... lifejackets, if carried, must be of the same or similar design as required by § 199.70(b). (5) Containers for... appliance in accordance with § 199.170(c)(2). (13) Immersion suits must be carried on all cargo vessels...

  19. 46 CFR 199.03 - Relationship to international standards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... supplemented by a Record of Equipment, or a valid Cargo Ship Safety Equipment Certificate supplemented by a... lifejackets, if carried, must be of the same or similar design as required by § 199.70(b). (5) Containers for... appliance in accordance with § 199.170(c)(2). (13) Immersion suits must be carried on all cargo vessels...

  20. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  1. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  2. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  3. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  4. 46 CFR 199.140 - Stowage of rescue boats.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Stowage of rescue boats. 199.140 Section 199.140... boats. (a) General. Rescue boats must be stowed— (1) To be ready for launching in not more than 5 minutes. (2) In a position suitable for launching and recovery; (3) In a way that neither the rescue boat...

  5. The “gating” residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition

    PubMed Central

    Milczek, Erika M.; Binda, Claudia; Rovida, Stefano; Mattevi, Andrea; Edmondson, Dale E.

    2011-01-01

    Summary The major structural difference between human monoamine oxidases A (MAO A) and B (MAO B) is that MAO A has a monopartite substrate cavity of ~550 Å3 volume and MAO B contains a dipartite cavity structure with volumes of ~290 Å3 (entrance cavity) and ~400 Å3 (substrate cavity). Ile199 and Tyr326 side chains separate these two cavities in MAO B. To probe the function of these gating residues, Ile199Ala and Ile199Ala Tyr326Ala mutant forms of MAO B were investigated. Structural data on the Ile199Ala MAO B mutant show no alterations in active site geometries compared to WT enzyme while the Ile199Ala-Tyr326Ala MAO B mutant exhibits alterations in residues 100–103 which are part of the loop gating the entrance to the active site. Both mutant enzymes exhibit catalytic properties with increased amine KM but unaltered kcat values. The altered KM values on mutation are attributed to the influence of the cavity structure in the binding and subsequent deprotonation of the amine substrate. Both mutant enzymes exhibit weaker binding affinities relative to WT enzyme for small reversible inhibitors. Ile199Ala MAO B exhibits an increase in binding affinity for reversible MAO B specific inhibitors which bridge both cavities. The Ile199Ala-Tyr326Ala double mutant exhibits inhibitor binding properties more similar to those of MAO A than to MAO B. These results demonstrate the bipartite cavity structure in MAO B plays an important role in substrate and inhibitor recognition to distinguish its specificities from those of MAO A and provides insights into specific reversible inhibitor design for these membrane-bound enzymes. PMID:21978362

  6. miR-199a-5p regulates HIF-1α and OSGIN2 and its expression is correlated to soft-tissue sarcoma patients' outcome

    PubMed Central

    Keßler, Jacqueline; Rot, Swetlana; Bache, Matthias; Kappler, Matthias; Würl, Peter; Vordermark, Dirk; Taubert, Helge; Greither, Thomas

    2016-01-01

    Soft tissue sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin. Partly due to hypoxia, an aggressive and radioresistant phenotype frequently develops, resulting in poorer patient outcome. microRNAs (miRNAs) are tiny, non-coding regulators of gene expression and in situations of cellular stress situations may predict clinical progression and patient outcome. In the present study, hypoxia-associated miR-199a-5p expression in 96 soft tissue sarcoma samples was analysed by reverse transcription-quantitative polymerase chain reaction and associations between miR-199a-5p expression and patient clinicopathological characteristics and survival were measured. Additionally, luciferase reporter assays analyzed the post-transcriptional regulation of hypoxia-associated genes hypoxia-inducible factor 1α (HIF-1α), oxidative stress induced growth inhibitor 2 (OSGIN2) and vascular endothelial growth factor (VEGF) by miR-199a-5p. Survival analyses indicated that low expression of miR-199a-5p was significantly correlated with poorer tumor-specific survival (univariate Cox's-Regression analyses; relative risk=1.92, P=0.029). Furthermore, it was demonstrated that the 3′UTR of HIF-1α and OSGIN2 genes were regulated by miR-199a-5p in-vitro, although the 3′UTR of VEGF was not. To the best of our knowledge, this is the first report demonstrating the regulation of the 3′untranslated region of the OSGIN2 gene by miR-199a-5p and a significant correlation between low miR-199a-5p expression and a poor outcome of patients with soft tissue sarcoma. PMID:28101243

  7. Clinical Interpretation of Elevated CA 19-9 Levels in Obstructive Jaundice Following Benign and Malignant Pancreatobiliary Disease.

    PubMed

    Kim, Min Seong; Jeon, Tae Joo; Park, Ji Young; Choi, Jeongmin; Shin, Won Chang; Park, Seong Eun; Seo, Ji Young; Kim, Young Moon

    2017-08-25

    Elevated carbohydrate antigen (CA) 19-9 level may be unable to differentiate between benign and malignant pancreatobiliary disease with obstructive jaundice. The study aims to determine the clinical interpretation and the diagnostic value of CA 19-9 level in pancreatobiliary diseases with coexistent obstructive jaundice. We retrospectively reviewed the data of 981 patients who underwent biliary drainage due to obstructive jaundice following pancreatobiliary disease at Sanggye Paik Hospital for 5 years. 114 patients with serial follow-up data for CA 19-9 level were included in this study (80 patients with malignancy and 34 patients with benign diseases). We compared the levels of CA 19-9 levels and the biochemical value before and after biliary drainage. The rate of CA 19-9 elevation (>37 U/mL) was significantly different between the benign group and the malignant group (59% vs. 90%, p=0.001). Despite the decrease in serum bilirubin after biliary drainage, CA 19-9 levels remained elevated in 12% of patients in the benign group and in 63% of patients in the malignant group (p<0.001). Finally, 12% of patients in the benign group turned out to have malignant disease. A receiver operating characteristic analysis provided a cut-off value of 38 U/mL for differentiating benign disease from malignant disease after biliary drainage (area under curve, 0.787; 95% confidence interval, 0.703 to 0.871; sensitivity, 62%; specificity, 88%). This study suggested that we should consider the possibility of malignant causes if the CA 19-9 levels remain high or are more than 38 U/mL after resolution of biliary obstruction.

  8. Search for a Permanent Electric Dipole Moment on MERCURY-199 Atoms as a Test of Time Reversal Symmetry

    NASA Astrophysics Data System (ADS)

    Jacobs, James Patrick

    Optically pumped atomic oscillators driven with a modulated light source have been used to measure the Permanent Electric Dipole Moment (PEDM) of the ^{199}Hg atom. A nonzero PEDM on the ground state of ^{199} Hg would be a direct violation of time reversal symmetry. The measurement was obtained by searching for a relative shift in the resonance frequency of the processing nuclear magnetic moments when an externally applied electric field was reversed relative to an externally applied magnetic field. The null result, d(^{199} Hg) = (.3 +/- 5.7 +/- 5.0) times 10 ^{-28} ecdotcm, represents nearly a factor of 15 improvement over previous ^{199}Hg measurements, and a factor of 25 improvement in statistical uncertainty. When combined with theoretical calculations, the result sets stringent limits on possible sources of time reversal symmetry violation in atomic systems.

  9. Perceived organizational support and extra-role performance: which leads to which?

    PubMed

    Chen, Zhixia; Eisenberger, Robert; Johnson, Kelly M; Sucharski, Ivan L; Aselage, Justin

    2009-02-01

    L. Rhoades and R. Eisenberger (2002) reported the meta-analytic finding of a highly statistically significant relation between perceived organizational support (POS) and performance but concluded that the reviewed studies' methodology allowed no conclusion concerning the direction of the association. To investigate this issue, the authors assessed POS and extra-role performance 2 times, separated by a 3-year interval, among 199 employees of an electronic and appliance sales organization. Using a cross-lagged panel design, the authors found that POS was positively associated with a temporal change in extra-role performance. In contrast, the relation between extra-role performance and temporal change in POS was not statistically significant. These findings provide evidence that POS leads to extra-role performance.

  10. 45 CFR 1.2 - Subject matter of Office of the Secretary regulations in parts 1-99.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... subject matter of the regulations in Parts 1-99 of this title includes: • Civil rights/nondiscrimination... regulations in parts 1-99. 1.2 Section 1.2 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL.... • Grants and letter of credit administration, property, hearing rights: Parts 10, 12, 15, 16, 74, 75, 77...

  11. 45 CFR 1.2 - Subject matter of Office of the Secretary regulations in parts 1-99.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... subject matter of the regulations in Parts 1-99 of this title includes: • Civil rights/nondiscrimination... regulations in parts 1-99. 1.2 Section 1.2 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL.... • Grants and letter of credit administration, property, hearing rights: Parts 10, 12, 15, 16, 74, 75, 77...

  12. 45 CFR 1.2 - Subject matter of Office of the Secretary regulations in parts 1-99.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... subject matter of the regulations in Parts 1-99 of this title includes: • Civil rights/nondiscrimination... regulations in parts 1-99. 1.2 Section 1.2 Public Welfare Department of Health and Human Services GENERAL.... • Grants and letter of credit administration, property, hearing rights: Parts 10, 12, 15, 16, 74, 75, 77...

  13. Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

    PubMed

    Jo, Jae-Cheol; Ryu, Min-Hee; Koo, Dong-Hoe; Ryoo, Baek-Yeol; Kim, Hwa Jung; Kim, Tae Won; Choi, Kee Don; Lee, Gin Hyug; Jung, Hwoon-Yong; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kim, Jin-Ho; Kang, Yoon-Koo

    2013-12-01

    To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis. © 2012 Wiley Publishing Asia Pty Ltd.

  14. High Expression of P38α and Preoperative Carbohydrate Antigen 19-9 Indicate Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

    PubMed

    Chen, Jionghuang; Zhao, Ting; Jia, Shengnan; Zhou, Senhao; Zhou, Liangjing; Wang, Shaowen; Ding, Guoping; Jiang, Guixing; Cao, Liping

    2018-01-01

    Background: P38α is a ubiquitous protein kinase, which plays diverse roles in cancers. Surprisingly, P38α functions vary markedly in different cancers (e.g., cancer suppressor vs cancer promoter). However, there is no report on the expression of P38α, the family's most important member, in pancreatic ductal adenocarcinoma (PDAC) and its association with clinicoathological parameters and patients' prognosis. Materials and methods: We retrospectively analyzed 152 patients who underwent surgery and were pathologically diagnosed with PDAC from September 2013 to September 2015. We used immunohistochemistry to detect P38α expression in tumor and adjacent normal tissues. The significance of the association between P38α and clinicopathological parameters was evaluated using the χ² test and t tests. The Kaplan-Meier method was used to assess the association between P38α expression and preoperative carbohydrate antigen 19-9 (CA19-9) levels and patients' overall survival. The Cox regression model was used to analyze the association between clinicopathological parameters, P38α and preoperative CA19-9 levels, and prognosis. Statistical significance was defined as P < 0.05. Results: P38α was expressed in 63.16% tumor tissues of PDAC, which was significantly higher compared with the adjacent normal tissues (26.32%, P < 0.001). High expression of P38α was associated with patients' histological grade ( P = 0.013), lymphatic metastasis ( P = 0.025) and TNM stage ( P = 0.048). The median survival time of the P38α-high group was 9.2 months, which was shorter compared with that of the P38α-low group (17.3 months, P = 0.011). The median survival time of the CA19-9 > 43.63 group was 11.1 months shorter than that of the CA19-9 < 43.63 group (24.8 months, P < 0.001). The Cox regression model revealed that age ( P = 0.003), lymphatic invasion ( P = 0.015), TNM stage ( P = 0.003), histological grade ( P < 0.001), preoperative CA19-9 ( P = 0.049), and P38α expression ( P = 0.008) were statistically significant independent risk factors affecting prognosis. Specifically, overall survival was 28.4 months in the P38α-low and CA19-9 < 43.63 groups, 16.3 months in the P38α-high or CA19-9 > 43.63 groups, and 9.7 months in the P38α-high and CA19-9 > 43.63 groups ( P < 0.001). Conclusions: High expression of P38α was significantly associated with histological grade, lymphatic metastasis, TNM stage and prognosis in patients with PDAC. P38α and preoperative CA19-9 levels were independent risk factors affecting the prognosis of PDAC patients. High expression of p38α and preoperative carbohydrate antigen 19-9 indicate poor prognosis in patients with PDAC.

  15. 49 CFR 199.103 - Use of persons who fail or refuse a drug test.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.103 Use of persons who fail or refuse a drug test. (a) An operator may not knowingly use as an employee any person who— (1) Fails a drug test required by... 49 Transportation 3 2013-10-01 2013-10-01 false Use of persons who fail or refuse a drug test. 199...

  16. 49 CFR 199.103 - Use of persons who fail or refuse a drug test.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.103 Use of persons who fail or refuse a drug test. (a) An operator may not knowingly use as an employee any person who— (1) Fails a drug test required by... 49 Transportation 3 2014-10-01 2014-10-01 false Use of persons who fail or refuse a drug test. 199...

  17. 49 CFR 199.103 - Use of persons who fail or refuse a drug test.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.103 Use of persons who fail or refuse a drug test. (a) An operator may not knowingly use as an employee any person who— (1) Fails a drug test required by... 49 Transportation 3 2011-10-01 2011-10-01 false Use of persons who fail or refuse a drug test. 199...

  18. 49 CFR 199.103 - Use of persons who fail or refuse a drug test.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.103 Use of persons who fail or refuse a drug test. (a) An operator may not knowingly use as an employee any person who— (1) Fails a drug test required by... 49 Transportation 3 2012-10-01 2012-10-01 false Use of persons who fail or refuse a drug test. 199...

  19. 49 CFR 199.103 - Use of persons who fail or refuse a drug test.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.103 Use of persons who fail or refuse a drug test. (a) An operator may not knowingly use as an employee any person who— (1) Fails a drug test required by... 49 Transportation 3 2010-10-01 2010-10-01 false Use of persons who fail or refuse a drug test. 199...

  20. 45 CFR 1.2 - Subject matter of Office of the Secretary regulations in parts 1-99.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Subject matter of Office of the Secretary regulations in parts 1-99. 1.2 Section 1.2 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION HHS'S REGULATIONS § 1.2 Subject matter of Office of the Secretary regulations in parts 1-99. This...

  1. Pancreatic Reference Set Application: Ivan Blasutig-University of Toronto (2014) — EDRN Public Portal

    Cancer.gov

    The primary objective of this study is to independently validate a panel of serum biomarkers for the early detection of pancreatic ductal adenocarcinoma (PDAC). The biomarkers were identified in various discovery studies performed in our laboratory1-6. We hypothesize that our candidate biomarkers can be used as a panel that will perform better than CA19.9 alone for the early detection of PDAC. Such a panel has the potential to lead to improved patient outcomes by enabling patients to receive treatment as early as possible.

  2. Studies on 66,67Ga- and 199Tl-poly(N-vinylpyrrolidone) complexes.

    PubMed

    Lahiri, Susanta; Sarkar, Soumi

    2007-03-01

    Gallium and thallium radionuclides have both diagnostic and therapeutic applications in the field of nuclear medicine. Poly(N-vinylpyrrolidone) (PVP) is routinely used as a drug base because of its excellent biocompatibility. In this paper, complex formation abilities between no-carrier-added (66,)(67)Ga/(199)Tl radionuclides and PVP have been studied. It has been found that aqueous 5% PVP solution can almost quantitatively back extract (66,)(67)Ga/(199)Tl radionuclides from an organic phase, which proves the complexing ability of PVP with (66,)(67)Ga/(199)Tl. Tl(3+) is more efficient to form Tl-PVP complexes than Tl(+). However, Tl(3+)-PVP complexes are less stable than Ga(3+)-PVP complexes.

  3. Reduced Limit on the Permanent Electric Dipole Moment of ^{199}Hg.

    PubMed

    Graner, B; Chen, Y; Lindahl, E G; Heckel, B R

    2016-04-22

    This Letter describes the results of the most recent measurement of the permanent electric dipole moment (EDM) of neutral ^{199}Hg atoms. Fused silica vapor cells containing enriched ^{199}Hg are arranged in a stack in a common magnetic field. Optical pumping is used to spin polarize the atoms orthogonal to the applied magnetic field, and the Faraday rotation of near-resonant light is observed to determine an electric-field-induced perturbation to the Larmor precession frequency. Our results for this frequency shift are consistent with zero; we find the corresponding ^{199}Hg EDM d_{Hg}=(-2.20±2.75_{stat}±1.48_{syst})×10^{-30}e cm. We use this result to place a new upper limit on the ^{199}Hg EDM |d_{Hg}|<7.4×10^{-30}e cm (95% C.L.), improving our previous limit by a factor of 4. We also discuss the implications of this result for various CP-violating observables as they relate to theories of physics beyond the standard model.

  4. Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p.

    PubMed

    Zuo, YaBei; Wang, YuZhao; Hu, HaiJuan; Cui, Wei

    2016-01-01

    This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism. Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry. Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level. These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p. © 2016 The Author(s) Published by S. Karger AG, Basel.

  5. Carbon Nanotube Matrix for Highly Sensitive Biosensors To Detect Pancreatic Cancer Biomarker CA19-9.

    PubMed

    Thapa, Anshu; Soares, Andrey Coatrini; Soares, Juliana Coatrini; Awan, Iram Taj; Volpati, Diogo; Melendez, Matias Eliseo; Fregnani, José Humberto Tavares Guerreiro; Carvalho, André Lopes; Oliveira, Osvaldo N

    2017-08-09

    Biosensors fabricated with nanomaterials promise faster, cheaper, and more efficient alternatives to traditional, often bulky devices for early cancer diagnosis. In this study, we fabricated a thin film sensing unit on interdigitated gold electrodes combining polyethyleneimine and carbon nanotubes in a layer by layer fashion, onto which antibodies anti-CA19-9 were adsorbed with a supporting layer of N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide solution. By use of impedance spectroscopy, the pancreatic cancer biomarker CA19-9 was detected in a buffer with limit of detection of 0.35 U/mL. This high sensitivity allowed for distinction between samples of blood serum from patients with distinct probabilities to develop pancreatic cancer. The selectivity of the biosensor was confirmed in subsidiary experiments with HT-29 and SW-620 cell lines and possible interferents, e.g., p53 protein, ascorbic acid, and glucose, where significant changes in capacitance could only be measured with HT-29 that contained the CA19-9 biomarker. Chemisorption of CA19-9 molecules onto the layer of anti-CA19-9 antibodies was the mechanism responsible for sensing while electrostatic interactions drove the adsorption of carbon nanotubes, according to polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). The adsorption behavior was successfully described by the Langmuir-Freundlich isotherm.

  6. Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

    PubMed Central

    Curtet, C; Tellier, C; Bohy, J; Conti, M L; Saccavini, J C; Thedrez, P; Douillard, J Y; Chatal, J F; Koprowski, H

    1986-01-01

    Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors. Images PMID:3459174

  7. CD44 is a direct target of miR-199a-3p and contributes to aggressive progression in osteosarcoma

    PubMed Central

    Gao, Yan; Feng, Yong; Shen, Jacson K.; Lin, Min; Choy, Edwin; Cote, Gregory M.; Harmon, David C.; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng

    2015-01-01

    Osteosarcoma is the most common primary bone malignancy in children and adolescents. Herein, we investigated the role of cluster of differentiation 44 (CD44), a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion, and migration in osteosarcoma. We constructed a human osteosarcoma tissue microarray with 114 patient tumor specimens, including tumor tissues from primary, metastatic, and recurrent stages, and determined the expression of CD44 by immunohistochemistry. Results showed that CD44 was overexpressed in metastatic and recurrent osteosarcoma as compared with primary tumors. Higher expression of CD44 was found in both patients with shorter survival and patients who exhibited unfavorable response to chemotherapy before surgical resection. Additionally, the 3′-untranslated region of CD44 mRNA was the direct target of microRNA-199a-3p (miR-199a-3p). Overexpression of miR-199a-3p significantly inhibited CD44 expression in osteosarcoma cells. miR-199a-3p is one of the most dramatically decreased miRs in osteosarcoma cells and tumor tissues as compared with normal osteoblast cells. Transfection of miR-199a-3p significantly increased the drug sensitivity through down-regulation of CD44 in osteosarcoma cells. Taken together, these results suggest that the CD44-miR-199a-3p axis plays an important role in the development of metastasis, recurrence, and drug resistance of osteosarcoma. Developing strategies to target CD44 may improve the clinical outcome of osteosarcoma. PMID:26079799

  8. Definitive Characterization of CA 19-9 in Resectable Pancreatic Cancer Using a Reference Set of Serum and Plasma Specimens.

    PubMed

    Haab, Brian B; Huang, Ying; Balasenthil, Seetharaman; Partyka, Katie; Tang, Huiyuan; Anderson, Michelle; Allen, Peter; Sasson, Aaron; Zeh, Herbert; Kaul, Karen; Kletter, Doron; Ge, Shaokui; Bern, Marshall; Kwon, Richard; Blasutig, Ivan; Srivastava, Sudhir; Frazier, Marsha L; Sen, Subrata; Hollingsworth, Michael A; Rinaudo, Jo Ann; Killary, Ann M; Brand, Randall E

    2015-01-01

    The validation of candidate biomarkers often is hampered by the lack of a reliable means of assessing and comparing performance. We present here a reference set of serum and plasma samples to facilitate the validation of biomarkers for resectable pancreatic cancer. The reference set includes a large cohort of stage I-II pancreatic cancer patients, recruited from 5 different institutions, and relevant control groups. We characterized the performance of the current best serological biomarker for pancreatic cancer, CA 19-9, using plasma samples from the reference set to provide a benchmark for future biomarker studies and to further our knowledge of CA 19-9 in early-stage pancreatic cancer and the control groups. CA 19-9 distinguished pancreatic cancers from the healthy and chronic pancreatitis groups with an average sensitivity and specificity of 70-74%, similar to previous studies using all stages of pancreatic cancer. Chronic pancreatitis patients did not show CA 19-9 elevations, but patients with benign biliary obstruction had elevations nearly as high as the cancer patients. We gained additional information about the biomarker by comparing two distinct assays. The two CA 9-9 assays agreed well in overall performance but diverged in measurements of individual samples, potentially due to subtle differences in antibody specificity as revealed by glycan array analysis. Thus, the reference set promises be a valuable resource for biomarker validation and comparison, and the CA 19-9 data presented here will be useful for benchmarking and for exploring relationships to CA 19-9.

  9. Biomarkers for early detection of pancreatic cancer — EDRN Public Portal

    Cancer.gov

    Background: The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools. Methods: Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Results: The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively correlated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected 1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone. Conclusions: Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combination offered some advantage of CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis, however further study will be needed to fully define the implications of these findings.

  10. A 3'-untranslated region (3'UTR) induces organ adhesion by regulating miR-199a* functions.

    PubMed

    Lee, Daniel Y; Shatseva, Tatiana; Jeyapalan, Zina; Du, William W; Deng, Zhaoqun; Yang, Burton B

    2009-01-01

    Mature microRNAs (miRNAs) are single-stranded RNAs of 18-24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3'UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3'UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3'UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3'UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3'UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3'UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3'UTR may be an approach in the development of gene therapy.

  11. MicroRNA‐199b Modulates Vascular Cell Fate During iPS Cell Differentiation by Targeting the Notch Ligand Jagged1 and Enhancing VEGF Signaling

    PubMed Central

    Chen, Ting; Kelaini, Sophia; Cochrane, Amy; Guha, Shaunta T.; Hu, Yanhua; Stitt, Alan W.; Xu, Qingbo

    2015-01-01

    Abstract Aims: Recent ability to derive endothelial cells (ECs) from induced pluripotent stem (iPS) cells holds a great therapeutic potential for personalized medicine and stem cell therapy. We aimed that better understanding of the complex molecular signals that are evoked during iPS cell differentiation toward ECs may allow specific targeting of their activities to enhance cell differentiation and promote tissue regeneration. Methods and Results: In this study, we have generated mouse iPS cells from fibroblasts using established protocol. When iPS cells were cultivated on type IV mouse collagen‐coated dishes in differentiation medium, cell differentiation toward vascular lineages were observed. To study the molecular mechanisms of iPS cell differentiation, we found that miR‐199b is involved in EC differentiation. A step‐wise increase in expression of miR‐199 was detected during EC differentiation. Notably, miR‐199b targeted the Notch ligand JAG1, resulting in vascular endothelial growth factor (VEGF) transcriptional activation and secretion through the transcription factor STAT3. Upon shRNA‐mediated knockdown of the Notch ligand JAG1, the regulatory effect of miR‐199b was ablated and there was robust induction of STAT3 and VEGF during EC differentiation. Knockdown of JAG1 also inhibited miR‐199b‐mediated inhibition of iPS cell differentiation toward smooth muscle markers. Using the in vitro tube formation assay and implanted Matrigel plugs, in vivo, miR‐199b also regulated VEGF expression and angiogenesis. Conclusions: This study indicates a novel role for miR‐199b as a regulator of the phenotypic switch during vascular cell differentiation derived from iPS cells by regulating critical signaling angiogenic responses. Stem Cells 2015;33:1405–1418 PMID:25535084

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

    Bell, Stephen G.; Hoskins, Nicola; Xu Feng

    Four (CYP195A2, CYP199A2, CYP203A1, and CYP153A5) of the seven P450 enzymes, and palustrisredoxin A, a ferredoxin associated with CYP199A2, from the metabolically diverse bacterium Rhodopseudomonas palustris have been expressed and purified. A range of substituted benzenes, phenols, benzaldehydes, and benzoic acids was shown to bind to the four P450 enzymes. Monooxygenase activity of CYP199A2 was reconstituted with palustrisredoxin A and putidaredoxin reductase of the P450cam system from Pseudomonas putida. We found that 4-ethylbenzoate and 4-methoxybenzoate were oxidized to single products, and 4-methoxybenzoate was demethylated to form 4-hydroxybenzoate. Crystals of substrate-free CYP199A2 which diffracted to {approx}2.0 A have been obtained.

  13. Mercury isotope constraints on the source for sediment-hosted lead-zinc deposits in the Changdu area, southwestern China

    NASA Astrophysics Data System (ADS)

    Xu, Chunxia; Yin, Runsheng; Peng, Jiantang; Hurley, James P.; Lepak, Ryan F.; Gao, Jianfeng; Feng, Xinbin; Hu, Ruizhong; Bi, Xianwu

    2018-03-01

    The Lanuoma and Cuona sediment-hosted Pb-Zn deposits hosted by Upper Triassic limestone and sandstone, respectively, are located in the Changdu area, SW China. Mercury concentrations and Hg isotopic compositions from sulfide minerals and potential source rocks (e.g., the host sedimentary rocks and the metamorphic basement) were investigated to constrain metal sources and mineralization processes. In both deposits, sulfide minerals have higher mercury (Hg) concentrations (0.35 to 1185 ppm) than the metamorphic basement rocks (0.05 to 0.15 ppm) and sedimentary rocks (0.02 to 0.08 ppm). Large variations of mass-dependent fractionation (3.3‰ in δ202Hg) and mass-independent fractionation (0.3‰ in Δ199Hg) of Hg isotopes were observed. Sulfide minerals have Hg isotope signatures that are similar to the hydrothermal altered rocks around the deposit, and similar to the metamorphic basement, but different from barren sedimentary rocks. The variation of Δ199Hg suggests that Hg in sulfides was mainly derived from the underlying metamorphic basement. Mercury isotopes could be a geochemical tracer in understanding metal sources in hydrothermal ore deposits.

  14. Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors.

    PubMed

    Hubálek, Frantisek; Binda, Claudia; Khalil, Ashraf; Li, Min; Mattevi, Andrea; Castagnoli, Neal; Edmondson, Dale E

    2005-04-22

    Several reversible inhibitors selective for human monoamine oxidase B (MAO B) that do not inhibit MAO A have been described in the literature. The following compounds: 8-(3-chlorostyryl)caffeine, 1,4-diphenyl-2-butene, and trans,trans-farnesol are shown to inhibit competitively human, horse, rat, and mouse MAO B with K(i) values in the low micromolar range but are without effect on either bovine or sheep MAO B or human MAO A. In contrast, the reversible competitive inhibitor isatin binds to all known MAO B and MAO A with similar affinities. Sequence alignments and the crystal structures of human MAO B in complex with 1,4-diphenyl-2-butene or with trans,trans-farnesol provide molecular insights into these specificities. These inhibitors span the substrate and entrance cavities with the side chain of Ile-199 rotated out of its normal conformation suggesting that Ile-199 is gating the substrate cavity. Ile-199 is conserved in all known MAO B sequences except bovine MAO B, which has Phe in this position (the sequence of sheep MAO B is unknown). Phe is conserved in the analogous position in MAO A sequences. The human MAO B I199F mutant protein of MAO B binds to isatin (K(i) = 3 microM) but not to the three inhibitors listed above. The crystal structure of this mutant demonstrates that the side chain of Phe-199 interferes with the binding of those compounds. This suggests that the Ile-199 "gate" is a determinant for the specificity of these MAO B inhibitors and provides a molecular basis for the development of MAO B-specific reversible inhibitors without interference with MAO A function in neurotransmitter metabolism.

  15. Prediagnostic Serum Biomarkers as Early Detection Tools for Pancreatic Cancer in a Large Prospective Cohort Study

    PubMed Central

    Nolen, Brian M.; Brand, Randall E.; Prosser, Denise; Velikokhatnaya, Liudmila; Allen, Peter J.; Zeh, Herbert J.; Grizzle, William E.; Lomakin, Aleksey; Lokshin, Anna E.

    2014-01-01

    Background The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools. Methods Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Results The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone. Conclusions Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection. PMID:24747429

  16. A 3′-Untranslated Region (3′UTR) Induces Organ Adhesion by Regulating miR-199a* Functions

    PubMed Central

    Lee, Daniel Y.; Shatseva, Tatiana; Jeyapalan, Zina; Du, William W.; Deng, Zhaoqun; Yang, Burton B.

    2009-01-01

    Mature microRNAs (miRNAs) are single-stranded RNAs of 18–24 nucleotides that repress post-transcriptional gene expression. However, it is unknown whether the functions of mature miRNAs can be regulated. Here we report that expression of versican 3′UTR induces organ adhesion in transgenic mice by modulating miR-199a* activities. The study was initiated by the hypothesis that the non-coding 3′UTR plays a role in the regulation of miRNA function. Transgenic mice expressing a construct harboring the 3′UTR of versican exhibits the adhesion of organs. Computational analysis indicated that a large number of microRNAs could bind to this fragment potentially including miR-199a*. Expression of versican and fibronectin, two targets of miR-199a*, are up-regulated in transgenic mice, suggesting that the 3′UTR binds and modulates miR-199a* activities, freeing mRNAs of versican and fibronectin from being repressed by miR-199a*. Confirmation of the binding was performed by PCR using mature miR-199a* as a primer and the targeting was performed by luciferase assays. Enhanced adhesion by expression of the 3′UTR was confirmed by in vitro assays. Our results demonstrated that upon arrival in cytoplasm, miRNA activities can be modulated locally by the 3′UTR. Our assay may be developed as sophisticated approaches for studying the mutual regulation of miRNAs and mRNAs in vitro and in vivo. We anticipate that expression of the 3′UTR may be an approach in the development of gene therapy. PMID:19223980

  17. Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor.

    PubMed

    Alanbay, Ibrahim; Akturk, Erhan; Coksuer, Hakan; Ercan, Mutlu; Karaşahin, Emre; Dede, Murat; Yenen, Mufit Cemal; Ozan, Hakan; Baser, Iskender

    2012-06-01

    The aim of this study was to assess the prognostic values of risk of malignancy index (RMI IV), ultrasound score, menopausal status, and serum CA125 and CA19-9 level in patients with borderline ovarian tumor (BOT). Fifty women having borderline ovarian tumor (BOT) and 5O individuals with benign adnexal mass were enrolled in this retrospective study. The sensitivity, specificity, positive predictive values, negative predictive values and diagnostic accuracy of preoperative serum levels of the CA125 and CA19-9, ultrasound findings and menopausal status, and RMI IV were calculated for prediction of discrimination between BOTs and benign adnexal masses and the results were compared. The RMI IV was the best method for discrimination between BOTs and benign adnexal masses and was more accurate than the other parameters. When Receiver Operator Characteristic area under the curves for menopausal status was analyzed, serum CA 125 and CA19-9 level, ultrasound score, RMI IV(CA125), and RMI IV(CA19-9) were, 0.580, 0.625, 0.548, 0.694, 0.734 and 0.711, respectively. The best RMI IV cut-off was found to be 200 for discrimination of benign and BOT lesions. In the RMI formulation, replacing CA125 with CA19-9 didn't affect RMI IV sensitivity and specificity for discrimination. Compared to ultrasound, menopausal status, CA-125, CA19-9, the RMI IV was found to be the best predictive method for differentiation of BOTs from benign adnexal masses. RMI IV cut-off value of 200 is suitable for differentiation of benign and BOT's.

  18. 26 CFR 1.199-9 - Application of section 199 to pass-thru entities for taxable years beginning on or before May 17...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... regardless of the amount of the partner's share of W-2 wages (as defined in § 1.199-2(e)) of the partnership... at the entity level— (A) The partner is allocated its share of QPAI and W-2 wages (as defined in § 1...)(A)(iii), respectively) are combined with the partner's QPAI and W-2 wages from other sources; (B...

  19. TPS and CA 19-9 measurements in the follow-up of patients with pancreatic cancer and chronic pancreatitis.

    PubMed

    Slesak, B; Harlozinska-Szmyrka, A; Knast, W; Sedlaczek, P; Einarsson, R; van Dalen, A

    2004-01-01

    The aim of this study was to assess the value of TPS and CA 19-9 in a long-term follow-up analysis of 11 patients with chronic pancreatitis (CP) and 15 patients with pancreatic cancer (PC). In all monitored patients with chronic pancreatitis the initial TPS level was below 200 U/L, whereas CA 19-9 was elevated in two of them. In one patient a dramatic increase in the TPS concentration (820 U/L) was measured at the last follow-up visit (after 8.6 months), which led to the detection of PC. In all patients with PC the preoperative TPS level exceeded 200 U/L, whereas CA 19-9 was elevated in only nine patients. After the Kausch-Whipple operation 11 patients showed no evidence of disease and in eight of these patients both TPS and CA 19-9 were within the reference range; however, in three patients liver metastases were detected after 8-24 months from the last tumor marker measurement. In four of the 15 patients both markers were elevated at the end of the follow-up period and distant metastases were clinically confirmed. Our results indicate that in patients with CP and PC undergoing long-term follow-up, TPS reflects the clinical status of patients more accurately than CA 19-9.

  20. [Diagnostic values of type III Procollagen N-terminal peptide and combination assay of type III procollagen N-terminal peptide with CEA and CA 19-9 in gastric cancer].

    PubMed

    Akazawa, S; Harada, A; Futatsuki, K

    1984-07-01

    It is known that interstitial collagens are initially synthesized as precursors (procollagen), which possess extra peptide segments at both ends of the molecules. The authors attempted to detect the aminoterminal peptide of type III procollagen (type III-N-peptide) and also to measure the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) together in sera of patients with gastric cancer. The results showed that: (1) mean serum levels and positive ratios of the type III-N-peptide increased as the clinical stage of the patients with gastric cancer advanced; (2) serum levels of the type III-N-peptide were not correlated either with those of CEA or CA 19-9; (3) positive ratios of type III-N-peptide, CEA and CA 19-9 were 51.7%, 44.8% and 48.3%, respectively: (4) positive ratio in combination of the type III-N-peptide with CEA was 69.3% and that in combination of the type III-N-peptide with CEA and CA 19-9 was 72.4%. These results suggest that type III-N-peptide is available for diagnosis of gastric cancer and, that the combination assay of type III-N-peptide with CEA and CA 19-9 is more effective than a single assay for diagnosis.

  1. [Blood and urine lead levels in children with attention deficit hyperactivity disorder].

    PubMed

    Sánchez-Villegas, M del Carmen S; Cortés-Vargas, Astrid; Hidalgo-Luna, Ricardo Gerardo; Alam-Escamilla, David Abraham; Vargas-García, Víctor Manuel; Loría-Castellanos, Jorge

    2014-01-01

    Attention deficit hyperactivity disorder is the most common neuropsychiatric disorder in children; symptoms can persist into adult life by 60 %. Our objective was to quantify the levels of lead in blood and urine in pediatric patients with attention deficit hyperactivity disorder. We did an observational study which included a captive population of children diagnosed with attention deficit hyperactivity disorder in the mental health service of Hospital General, from Centro Médico Nacional La Raza. Lead levels were determined in blood and urine by atomic absorption technique. We included 39 patients, 932 % male, with a mean age of 9.2 ± 2.16 years. The deficit and hyperactivity disorder combined type was the most frequent (69.2 %); 49 % of patients were found with toxic lead levels in blood (above 10 mg/dL); 17.9 % with stage III and 5.12 % with stage IV, according to the Mexican Official Standard (NOM-199-SSA-2000). Significant association was found between blood lead levels and the clinical expression of attention deficit hyperactivity disorder. Levels of lead exposure during early childhood have been shown to be inversely proportional to neurological development in the first seven years of life. Data results are insufficient to relate them with causality.

  2. 49 CFR 199.225 - Alcohol tests required.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Prevention Program § 199.225 Alcohol tests required. Each operator shall conduct the following types of... to unannounced follow-up alcohol testing as directed by a substance abuse professional in accordance...

  3. 49 CFR 199.225 - Alcohol tests required.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Prevention Program § 199.225 Alcohol tests required. Each operator shall conduct the following types of... to unannounced follow-up alcohol testing as directed by a substance abuse professional in accordance...

  4. 49 CFR 199.225 - Alcohol tests required.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Prevention Program § 199.225 Alcohol tests required. Each operator shall conduct the following types of... to unannounced follow-up alcohol testing as directed by a substance abuse professional in accordance...

  5. 49 CFR 199.225 - Alcohol tests required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Prevention Program § 199.225 Alcohol tests required. Each operator shall conduct the following types of... to unannounced follow-up alcohol testing as directed by a substance abuse professional in accordance...

  6. 49 CFR 199.225 - Alcohol tests required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Prevention Program § 199.225 Alcohol tests required. Each operator shall conduct the following types of... to unannounced follow-up alcohol testing as directed by a substance abuse professional in accordance...

  7. Potential diagnostic performance of contrast-enhanced ultrasound and tumor markers in differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and cholangiocarcinoma.

    PubMed

    Huang, Xiao-Wen; Huang, Yang; Chen, Li-da; Wang, Zhu; Yang, Zheng; Liu, Jin-Ya; Xie, Xiao-Yan; Lu, Ming-De; Shen, Shun-Li; Wang, Wei

    2018-04-01

    To evaluate the diagnostic performance of the combination of tumor markers [alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9)] and imaging features in differentiating combined hepatocellular-cholangiocarcinoma (CHC) from hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Forty consecutive patients with pathologically proven CHC were retrospectively evaluated with contrast-enhanced ultrasound (CEUS). Additionally, 40 HCC and 40 CC patients who were randomly selected from the same period served as a control group. Images were classified as HCC-like or CC-like pattern according to CEUS guidelines recommended by World and European Federation for Ultrasound in Medicine and Biology (WFUMB-EFSUMB). The diagnostic criteria of CHC were defined as follows: (1) both AFP and CA19-9 are simultaneously elevated (AFP > 20 ng/ml and CA19-9 > 100 units/ml); or (2) elevated AFP with a CC-like pattern on CEUS and without elevated CA19-9 level; or (3) elevated CA19-9 with an HCC-like pattern on CEUS and without elevated AFP level. The diagnostic tests were performed with calculation of the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). For the 40 CHC patients, the rates of elevated AFP and CA19-9 serology were 55.0 and 30.0%, respectively. Twenty-three (57.5%) patients exhibited an HCC-like pattern, and 15 (37.5%) showed a CC-like pattern. After applying the above diagnostic criteria of CHC in the 120 patients, the sensitivity, specificity, PPV, NPV, accuracy, and AUC were 32.5, 93.8, 72.2, 73.5, 73.3, and 0.631%, respectively. When the actual prevalence rate (0.4-14.3%) was taken into account, the PPV and NPV were modified from 2.1 to 46.7% and 89.3 to 99.7%, respectively. The combination of enhancement patterns on CEUS and serum tumor markers (AFP and CA19-9) may be a potentially specific diagnostic method to differentiate CHC from HCC and CC.

  8. 32 CFR 199.24 - TRICARE Reserve Select.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.24 TRICARE Reserve... rules and procedures as may be appropriate to the area involved. (4) Terminology. Certain terminology is...

  9. 32 CFR 199.24 - TRICARE Reserve Select.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.24 TRICARE Reserve... rules and procedures as may be appropriate to the area involved. (4) Terminology. Certain terminology is...

  10. 32 CFR 199.24 - TRICARE Reserve Select.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.24 TRICARE Reserve... rules and procedures as may be appropriate to the area involved. (4) Terminology. Certain terminology is...

  11. 32 CFR 199.24 - TRICARE Reserve Select.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.24 TRICARE Reserve... rules and procedures as may be appropriate to the area involved. (4) Terminology. Certain terminology is...

  12. 49 CFR 199.5 - DOT procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING General § 199.5... to the requirements of this part and DOT Procedures. Terms and concepts used in this part have the...

  13. 32 CFR 199.24 - TRICARE Reserve Select.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.24 TRICARE Reserve... rules and procedures as may be appropriate to the area involved. (4) Terminology. Certain terminology is...

  14. 40 CFR 464.22 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....399 TSS 1.52 0.598 pH (1) (1) 1 Within the range of 7.0 to 10.0 at all times. Maximum for any 1 day....39 0.0088 Zinc (T) 1.14 0.43 0.0108 Oil and grease 30 10 0.199 TSS 38 15 0.399 pH (3) (3) (3) 1 kg....506 Lead (T) 0.952 0.47 Zinc (T) 1.37 0.518 Oil and grease 36.2 12.1 TSS 45.8 18.1 pH (1) (1) 1 Within...

  15. CA 19-9 (Cancer Antigen 19-9)

    MedlinePlus

    ... Cytomegalovirus (CMV) Tests D-dimer Dengue Fever Testing Des-gamma-carboxy prothrombin (DCP) DHEAS Diabetes-related Autoantibodies ... article.cfm?id=296. Accessed June 28, 2016. De Paula JMP, Toranzo EM, Borge LG, Hidalgo SF. ...

  16. Comparison of different hadron production models for the study of π±, K±, protons and antiprotons production in proton-carbon interactions at 90 GeV/c

    NASA Astrophysics Data System (ADS)

    Ajaz, M.; Ali, Y.; Ullah, S.; Ali, Q.; Tabassam, U.

    2018-05-01

    In this research paper, comprehensive results on the double differential yield of π± and K± mesons, protons and antiprotons as a function of laboratory momentum in several polar angle ranges from 0-420 mrad for pions, 0-360 mrad for kaons, proton and antiproton are reported. EPOS 1.99, EPOS-LHC and QGSJETII-04 models are used to perform simulations. The predictions of these models at 90 GeV/c are plotted for comparison, which shows that QGSJETII-04 model gives overall higher yield for π+ mesons in the polar angle interval of 0-40 mrad but for the π‑ the yield is higher only up to 20 mrad. For π+ mesons after 40 mrad, EPOS-LHC predicts higher yield as compared to EPOS 1.99 and QGSJETII-04 while EPOS-LHC and EPOS 1.99 give similar behavior in these two intervals. However, for π‑ mesons EPOS-LHC and EPOS 1.99 give similar behavior in these two intervals. For of K± mesons, QGSJETII-04 model gives higher predictions in all cases from 0-300 mrad, while EPOS 1.99 and EPOS-LHC show similar distributions. In case of protons, all models give similar distribution but this is not true for antiproton. All models are in good agreement for p > 20 GeV/c. EPOS 1.99 produce lower yield compared to the other two models from 60-360 mrad polar angle interval.

  17. CA 19-9 as a Marker of Survival and a Predictor of Metastization in Cholangiocarcinoma

    PubMed Central

    Coelho, Rosa; Silva, Marco; Rodrigues-Pinto, Eduardo; Cardoso, Hélder; Lopes, Susana; Pereira, Pedro; Vilas-Boas, Filipe; Santos-Antunes, João; Costa-Maia, José; Macedo, Guilherme

    2017-01-01

    Background Cholangiocarcinoma is the second most frequent primitive liver malignancy and is responsible for 3% of the malignant gastrointestinal neoplasms. The aims of this study were to determine the association of serum levels of CA 19-9 at diagnosis with other clinical data and serum liver function tests and to identify possible factors that influence the survival rates during follow-up. Methods Retrospective observational study of 89 patients with a diagnosis of cholangiocarcinoma followed at the Department of Gastroenterology during 5 years. Statistical analyses were performed using SPSS version 20.0. Results Patients were followed up for a median time of 127 days (IQR: 48–564), and the median age at diagnosis was 71.0 years (IQR: 62.0–77.5). The median survival rate was 14.0 months (IQR: 4.3–23.7), and the mortality rate was 79%. Patients with CA 19-9 levels ≥103 U/L had lower albumin levels and higher levels of alanine aminotransferase and γ-glutamyltransferase. CA 19-9 levels ≥103 U/L were associated with a higher probability of metastization (p = 0.001) and lower rates of treatment with curative intent (p = 0.024). In a multivariate analysis, CA 19-9 levels <103 U/L and surgery were independent predictors of survival. Conclusion Predictive factors for overall survival were identified, namely presence of metastasis, surgery, and chemotherapy. CA 19-9 levels ≥103 U/L were predictive factors for survival and metastization. PMID:28848795

  18. NGAL, MIC-1 and CA19-9 in Pancreatic Juice: Pathobiological Implications in Diagnosing Benign and Malignant Disease of the Pancreas

    PubMed Central

    KAUR, SUKHWINDER; BAINE, MICHAEL J.; GUHA, SUSHOVAN; OCHI, NOBUO; CHAKRABORTY, SUBHANKAR; MALLYA, KAVITA; THOMAS, COLLEEN; CROOK, JULIA; WALLACE, MICHAEL B.; WOODWARD, TIMOTHY A.; JAIN, MANEESH; SINGH, SHAILENDER; SASSON, AARON R.; SKINNER, VERNA; RAIMONDO, MASSIMO; BATRA, SURINDER K.

    2012-01-01

    Objective Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase–associated lipocalin (NGAL), macrophage inhibitory cytokine-1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases. Methods 105 chronic pancreatitis (CP), pancreatic cancer (PC), and non-pancreatic non-healthy (NPNH, patients with symptoms mimicking pancreatic disease but found to be free of pancreatic pathology) patients underwent endoscopic pancreatic juice collection following secretin-stimulation. NGAL and MIC-1 levels were measured by enzyme-linked immunosorbent assay while CA19-9 was measured by radioimmunoassay. Results NGAL, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of CP and PC patients as compared to NPNH controls (p<0.034). NGAL appeared most promising in differentiating diseased versus non-diseased pancreata (AUCs=0.88–0.91) while MIC-1 was found to be higher in PC than CP patients (p=0.043). Interestingly, MIC-1 levels in diabetic PC patients were higher than in non-diabetic PC (p=0.030) and diabetic CP patients (p=0.087). CA19-9 showed the least ability to distinguish patient groups (AUCs=0.61–0.76). Conclusions Pancreatic juice NGAL shows potential utility in establishing pancreatic etiology in the context of non-specific symptoms while MIC-1 may aid in differentiating PC from CP. PMID:23146921

  19. Occupational and environmental lead and PCB exposure at a scrap metal dealer

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

    Malkin, R.

    Blood lead levels (BPb) and serum polychlorinated biphenyl levels (PCB) were obtained from 17 employees at two adjacent scrap metal dealers. One facility was located outdoors, directly on top of soil known to be contaminated with lead and PCBs, and the other was located indoors with a concrete floor. BPbs ranged from 4.0 to 39.8 {mu}g/dl (mean 19.9 {mu}g/dl, geometric mean 17.5 {mu}g/dl) and PCB levels ranged from <1 to 65.3 ppb (mean 7.5 ppb). There was no significant difference in either BPb or serum PCB between the two sites. BPb was significantly correlated with the number of cigarettes smokedmore » at work, and both BPb and serum PCB were significantly related to eating lunch outside the lunchroom, suggesting hand-to-mouth contact as a source of exposure. The lack of difference in BPb between employees of the two scrap metal dealers suggests an ongoing source of lead exposure at the sites, other than the soil. 10 refs., 2 tabs.« less

  20. 40 CFR 267.199 - What inspection requirements must I meet?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... UNDER A STANDARDIZED PERMIT Tank Systems § 267.199 What inspection requirements must I meet? You must... within six months after initial installation and annually thereafter. (2) Inspect and/or test all sources...

  1. 40 CFR 267.199 - What inspection requirements must I meet?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... UNDER A STANDARDIZED PERMIT Tank Systems § 267.199 What inspection requirements must I meet? You must... within six months after initial installation and annually thereafter. (2) Inspect and/or test all sources...

  2. 40 CFR 267.199 - What inspection requirements must I meet?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... UNDER A STANDARDIZED PERMIT Tank Systems § 267.199 What inspection requirements must I meet? You must... within six months after initial installation and annually thereafter. (2) Inspect and/or test all sources...

  3. Hormesis and the salk polio vaccine.

    PubMed

    Calabrese, Edward J

    2012-01-01

    The production of the Salk vaccine polio virus by monkey kidney cells was generated using the synthetic tissue culture medium, Mixture 199. In this paper's retrospective assessment of this process, it was discovered that Mixture 199 was modified by the addition of ethanol to optimize animal cell survival based on experimentation that revealed a hormetic-like biphasic response relationship. This hormesis-based optimization procedure was then applied to all uses of Mixture 199 and modifications of it, including its application to the Salk polio vaccine during preliminary testing and in its subsequent major societal treatment programs.

  4. Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.

    PubMed

    Feng, Mei; Zhu, Jing; Liang, Liqun; Zeng, Ni; Wu, Yanqiu; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

    2017-04-01

    Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

  5. Clinical value of preoperative serum CA 19-9 and CA 125 levels in predicting the resectability of hilar cholangiocarcinoma.

    PubMed

    Hu, Hai-Jie; Mao, Hui; Tan, Yong-Qiong; Shrestha, Anuj; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

    2016-01-01

    To examine the predictive value of tumor markers for evaluating tumor resectability in patients with hilar cholangiocarcinoma and to explore the prognostic effect of various preoperative factors on resectability in patients with potentially resectable tumors. Patients with potentially resectable tumors judged by radiologic examination were included. The receiver operating characteristic (ROC) analysis was conducted to evaluate serum carbohydrate antigenic determinant 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125) and carcino embryonie antigen levels on tumor resectability. Univariate and multivariate logistic regression models were also conducted to analysis the correlation of preoperative factors with resectability. In patients with normal bilirubin levels, ROC curve analysis calculated the ideal CA 19-9 cut-off value of 203.96 U/ml in prediction of resectability, with a sensitivity of 83.7 %, specificity of 80 %, positive predictive value of 91.1 % and negative predictive value of 66.7 %. Meanwhile, the optimal cut-off value for CA 125 to predict resectability was 25.905 U/ml (sensitivity, 78.6 %; specificity, 67.5 %). In a multivariate logistic regression model, tumor size ≤3 cm (OR 4.149, 95 % CI 1.326-12.981, P = 0.015), preoperative CA 19-9 level ≤200 U/ml (OR 20.324, 95 % CI 6.509-63.467, P < 0.001), preoperative CA 125 levels ≤26 U/ml (OR 8.209, 95 % CI 2.624-25.677, P < 0.001) were independent determinants of resectability in patients diagnosed as hilar cholangiocarcinoma. Preoperative CA 19-9 and CA 125 levels predict resectability in patients with radiological resectable hilar cholangiocarcinoma. Increased preoperative CA 19-9 levels and CA 125 levels are associated with poor resectability rate.

  6. A preoperative serum signature of CEA+/CA125+/CA19-9 ≥ 1000 U/mL indicates poor outcome to pancreatectomy for pancreatic cancer.

    PubMed

    Liu, Liang; Xu, Huaxiang; Wang, Wenquan; Wu, Chuntao; Chen, Yong; Yang, Jingxuan; Cen, Putao; Xu, Jin; Liu, Chen; Long, Jiang; Guha, Sushovan; Fu, Deliang; Ni, Quanxing; Jatoi, Aminah; Chari, Suresh; McCleary-Wheeler, Angela L; Fernandez-Zapico, Martin E; Li, Min; Yu, Xianjun

    2015-05-01

    Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high-volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19-9 independently indicated surgical response in pancreatic cancer. Patients with CA19-9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19-9 levels decreased postoperatively. CEA and CA125 in the presence of CA19-9 ≥1000 U/mL could independently predict the non-decrease of CA19-9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p < 0.001) for the training cohort and 7.0 months vs. 18.2 months (p < 0.001) for the validation cohort and also suggested a higher prevalence of early distant metastasis after surgery. Resected patients with this proposed signature showed no survival advantage over patients in the locally advanced group who did not receive pancreatectomy. Therefore, a preoperative serum signature of CEA(+)/CA125(+)/CA19-9 ≥1000 U/mL is associated with poor surgical outcome and can be used to select appropriate patients with pancreatic cancer for pancreatectomy. © 2014 UICC.

  7. Imperforate hymen with elevated serum CA 125 and CA 19-9 levels.

    PubMed

    Sak, Muhammet Erdal; Evsen, Mehmet Siddik; Soydinc, Hatice Ender; Sak, Sibel; Yalinkaya, Ahmet

    2013-01-01

    To report the clinical characteristics of 14 patients with imperforate hymen and their levels of tumor markers (CA 19-9 and CA 125). Fourteen patients with imperforate hymen who followed-up between September 2006 and September 2010 in the Department of Obstetrics and Gynecology, Dicle University School of Medicine, Diyarbakir, Turkey, were evaluated retrospectively. The clinical features and the management of the patients are discussed. The mean age of the patients was 13.8 years. All patients had primary amenorrhea and pelvic pain. The most common clinical symptoms were cryptomenorrhea in 14 patients, pelvic pain in 11, palpable abdominal mass in 6, voiding difficulties in 7, and defecation problems in 2. In 6 patients with palpable pelvic mass, the mean + standard deviation values of tumor markers were as follows: CA 125, 84.0 +/- 23.7 and CA 19-9, 162 +/- 189. One week after surgery we measured CA 125 and CA 19-9 levels once again. The postoperative mean CA 125 level was 13.8 +/- 3.6, and the mean postoperative CA 19-9 level was 17.5 +/- 3.5. Preoperative levels of CA 125 and CA 19-9 were significantly higher than those of the postoperative period (p < 0.001 for both comparisons). Six patients were treated by T-shaped incision and 8 patients by a central surgical incision through the hymenal membrane. Diagnosis of imperforate hymen is very important before undergoing surgery in a different clinic. Many patients have seen several doctors before receiving a clear diagnosis and have had tumor markers evaluated because the presence of pelvic mass in patients suggests the possibility of a gynecologic malignancy. Imperforate hymen is one of the benign conditions that increase serum CA 125 and CA 19-9 levels and which is not listed in the classical medical textbooks. These markers are not needed for the diagnosis.

  8. 40. CAVEMAN BRIDGE, ROGUE RIVER, OREGON STATE HIGHWAY 199. GRANTS ...

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

    40. CAVEMAN BRIDGE, ROGUE RIVER, OREGON STATE HIGHWAY 199. GRANTS PASS, JOSEPHINE COUNTY, OREGON. LOOKING S. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  9. 39. CAVEMAN BRIDGE, ROGUE RIVER, OREGON STATE HIGHWAY 199. GRANTS ...

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

    39. CAVEMAN BRIDGE, ROGUE RIVER, OREGON STATE HIGHWAY 199. GRANTS PASS, JOSEPHINE COUNTY, OREGON. LOOKING SW. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  10. Higher mass-independent isotope fractionation of methylmercury in the pelagic food web of Lake Baikal (Russia).

    PubMed

    Perrot, Vincent; Pastukhov, Mikhail V; Epov, Vladimir N; Husted, Søren; Donard, Olivier F X; Amouroux, David

    2012-06-05

    Mercury undergoes several transformations that influence its stable isotope composition during a number of environmental and biological processes. Measurements of Hg isotopic mass-dependent (MDF) and mass-independent fractionation (MIF) in food webs may therefore help to identify major sources and processes leading to significant bioaccumulation of methylmercury (MeHg). In this work, δ(13)C, δ(15)N, concentration of Hg species (MeHg, inorganic Hg), and stable isotopic composition of Hg were determined at different trophic levels of the remote and pristine Lake Baikal ecosystem. Muscle of seals and different fish as well as amphipods, zooplankton, and phytoplankton were specifically investigated. MDF during trophic transfer of MeHg leading to enrichment of heavier isotopes in the predators was clearly established by δ(202)Hg measurements in the pelagic prey-predator system (carnivorous sculpins and top-predator seals). Despite the low concentrations of Hg in the ecosystem, the pelagic food web reveals very high MIF Δ(199)Hg (3.15-6.65‰) in comparison to coastal fish (0.26-1.65‰) and most previous studies in aquatic organisms. Trophic transfer does not influence MIF signature since similar Δ(199)Hg was observed in sculpins (4.59 ± 0.55‰) and seal muscles (4.62 ± 0.60‰). The MIF is suggested to be mainly controlled by specific physical and biogeochemical characteristics of the water column. The higher level of MIF in pelagic fish of Lake Baikal is mainly due to the bioaccumulation of residual MeHg that is efficiently turned over and photodemethylated in deep oligotrophic and stationary (i.e., long residence time) freshwater columns.

  11. Structural and biochemical analyses of a Clostridium perfringens sortase D transpeptidase

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

    Suryadinata, Randy, E-mail: randy.suryadinata@csiro.au; Seabrook, Shane A.; Adams, Timothy E.

    The structure of C. perfringens sortase D was determined at 1.99 Å resolution. Comparative biochemical and structural analyses revealed that this transpeptidase may represent a new subclass of the sortase D family. The assembly and anchorage of various pathogenic proteins on the surface of Gram-positive bacteria is mediated by the sortase family of enzymes. These cysteine transpeptidases catalyze a unique sorting signal motif located at the C-terminus of their target substrate and promote the covalent attachment of these proteins onto an amino nucleophile located on another protein or on the bacterial cell wall. Each of the six distinct classes ofmore » sortases displays a unique biological role, with sequential activation of multiple sortases often observed in many Gram-positive bacteria to decorate their peptidoglycans. Less is known about the members of the class D family of sortases (SrtD), but they have a suggested role in spore formation in an oxygen-limiting environment. Here, the crystal structure of the SrtD enzyme from Clostridium perfringens was determined at 1.99 Å resolution. Comparative analysis of the C. perfringens SrtD structure reveals the typical eight-stranded β-barrel fold observed in all other known sortases, along with the conserved catalytic triad consisting of cysteine, histidine and arginine residues. Biochemical approaches further reveal the specifics of the SrtD catalytic activity in vitro, with a significant preference for the LPQTGS sorting motif. Additionally, the catalytic activity of SrtD is most efficient at 316 K and can be further improved in the presence of magnesium cations. Since C. perfringens spores are heat-resistant and lead to foodborne illnesses, characterization of the spore-promoting sortase SrtD may lead to the development of new antimicrobial agents.« less

  12. Functional screening for miRNAs targeting Smad4 identified miR-199a as a negative regulator of TGF-β signalling pathway

    PubMed Central

    Zhang, Yan; Fan, Kai-Ji; Sun, Qiang; Chen, Ai-Zhong; Shen, Wen-Long; Zhao, Zhi-Hu; Zheng, Xiao-Fei; Yang, Xiao

    2012-01-01

    The transforming growth factor-β (TGF-β) signalling pathway participates in various biological processes. Dysregulation of Smad4, a central cellular transducer of TGF-β signalling, is implicated in a wide range of human diseases and developmental disorders. However, the mechanisms underlying Smad4 dysregulation are not fully understood. Using a functional screening approach based on luciferase reporter assays, we identified 39 microRNAs (miRNAs) as potential regulators of Smad4 from an expression library of 388 human miRNAs. The screening was supported by bioinformatic analysis, as 24 of 39 identified miRNAs were also predicted to target Smad4. MiR-199a, one of the identified miRNAs, was inversely correlated with Smad4 expression in various human cancer cell lines and gastric cancer tissues, and repressed Smad4 expression and blocked canonical TGF-β transcriptional responses in cell lines. These effects were dependent on the presence of a conserved, but not perfect seed paired, miR-199a-binding site in the Smad4 3′-untranslated region (UTR). Overexpression of miR-199a significantly inhibited the ability of TGF-β to induce gastric cancer cell growth arrest and apoptosis in vitro, and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis. In conclusion, our functional screening uncovers multiple miRNAs that regulate the cellular responsiveness to TGF-β signalling and reveals important roles of miR-199a in gastric cancer by directly targeting Smad4. PMID:22821565

  13. Hg Stable Isotope Time Trend in Ringed Seals Registers Decreasing Sea Ice Cover in the Alaskan Arctic.

    PubMed

    Masbou, Jérémy; Point, David; Sonke, Jeroen E; Frappart, Frédéric; Perrot, Vincent; Amouroux, David; Richard, Pierre; Becker, Paul R

    2015-08-04

    Decadal time trends of mercury (Hg) concentrations in Arctic biota suggest that anthropogenic Hg is not the single dominant factor modulating Hg exposure to Arctic wildlife. Here, we present Hg speciation (monomethyl-Hg) and stable isotopic composition (C, N, Hg) of 53 Alaskan ringed seal liver samples covering a period of 14 years (1988-2002). In vivo metabolic effects and foraging ecology explain most of the observed 1.6 ‰ variation in liver δ(202)Hg, but not Δ(199)Hg. Ringed seal habitat use and migration were the most likely factors explaining Δ(199)Hg variations. Average Δ(199)Hg in ringed seal liver samples from Barrow increased significantly from +0.38 ± 0.08‰ (±SE, n = 5) in 1988 to +0.59 ± 0.07‰ (±SE, n = 7) in 2002 (4.1 ± 1.2% per year, p < 0.001). Δ(199)Hg in marine biological tissues is thought to reflect marine Hg photochemistry before biouptake and bioaccumulation. A spatiotemporal analysis of sea ice cover that accounts for the habitat of ringed seals suggests that the observed increase in Δ(199)Hg may have been caused by the progressive summer sea ice disappearance between 1988 and 2002. While changes in seal liver Δ(199)Hg values suggests a mild sea ice control on marine MMHg breakdown, the effect is not large enough to induce measurable HgT changes in biota. This suggests that Hg trends in biota in the context of a warming Arctic are likely controlled by other processes.

  14. 36. MYRTLE CREEK BRIDGE, OREGON STATE HIGHWAY 199, AT END ...

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

    36. MYRTLE CREEK BRIDGE, OREGON STATE HIGHWAY 199, AT END OF STOUT GROVE ROAD. JOSEPHINE COUNTY, OREGON LOOKING WNW. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  15. 71. MYRTLE CREED BRIDGE, OREGON STATE HIGHWAY 199, AT END ...

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

    71. MYRTLE CREED BRIDGE, OREGON STATE HIGHWAY 199, AT END OF STOUT GROVE ROAD. JOSEPHINE COUNTY, OREGON. LOOKING WNW. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  16. Small RNA and transcriptome sequencing reveal the role of miR-199a-3p in inflammatory processes in cystic fibrosis airways.

    PubMed

    Bardin, Pauline; Marchal-Duval, Emmeline; Sonneville, Florence; Blouquit-Laye, Sabine; Rousselet, Nathalie; Le Rouzic, Philippe; Corvol, Harriet; Tabary, Olivier

    2018-05-07

    Cystic fibrosis (CF) is the most common lethal genetic disease, caused by CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations. CF is characterized by an ionic imbalance and thickened mucus, which impair mucociliary clearance, promote bacterial colonization, and the establishment of infection/inflammation cycles. However, the origin of this inflammation remains unclear, although microRNA (miRNA) are suspected to be involved. MiRNA are small non-coding RNA that bind to the 3'-untranslated regions (UTR) of target gene mRNA, thereby repressing their translation and/or inducing their degradation. The goal of this study was to investigate the role of microRNA associated with pulmonary inflammation in CF patients. Through the analysis of all miRNA (miRNome) in human primary air-liquid interface cultures, we demonstrated that miR-199a-3p is the only miRNA downregulated in CF patients compared to controls. Moreover, through RNA sequencing (transcriptome) analysis, we showed that 50% of all deregulated mRNA are linked directly or indirectly to the NF-κB pathway. To identify a specific target, we used bioinformatics analysis to predict whether miR-199a-3p targets the 3'-UTR of IKBKB which encodes IKKβ, a major protein in the NF-κB pathway. Subsequently, we used bronchial explants from CF patients to show that miR-199a-3p expression is downregulated compared to controls and inversely correlated with increases in expression of IKKβ and IL-8. Through functional studies, we showed that miR-199a-3p modulates the expression of IKBKB through a direct interaction at its 3'-UTR in bronchial epithelial cells from CF patients. In miR-199a-3p overexpression experiments, we demonstrated that for CF cells miR-199a-3p reduced IKKβ protein expression, NF-κB activity, and IL-8 secretion. Taken together, our findings show that miR-199a-3p plays a negative regulatory role in the NF-κB signalling pathway and that its low expression in CF patients contributes to chronic pulmonary inflammation. This article is protected by copyright. All rights reserved.

  17. Serum neuron-specific enolase, biogenic amino-acids and neurobehavioral function in lead-exposed workers from lead-acid battery manufacturing process.

    PubMed

    Ravibabu, K; Barman, T; Rajmohan, H R

    2015-01-01

    The interaction between serum neuron-specific enolase (NSE), biogenic amino-acids and neurobehavioral function with blood lead levels in workers exposed to lead form lead-acid battery manufacturing process was not studied. To evaluate serum NSE and biogenic amino-acids (dopamine and serotonin) levels, and neurobehavioral performance among workers exposed to lead from lead-acid storage battery plant, and its relation with blood lead levels (BLLs). In a cross-sectional study, we performed biochemical and neurobehavioral function tests on 146 workers exposed to lead from lead-acid battery manufacturing process. BLLs were assessed by an atomic absorption spectrophotometer. Serum NSE, dopamine and serotonin were measured by ELISA. Neurobehavioral functions were assessed by CDC-recommended tests---simple reaction time (SRT), symbol digit substitution test (SDST), and serial digit learning test (SDLT). There was a significant correlation (r 0.199, p<0.05) between SDST and BLL. SDLT and SRT had also a significant positive correlation (r 0.238, p<0.01). NSE had a negative correlation (r -0.194, p<0.05) with serotonin level. Multiple linear regression analysis revealed that both SRT and SDST had positive significant associations with BLL. SRT also had a positive significant association with age. Serum NSE cannot be used as a marker for BLL. The only domain of neurobehavioral function tests that is affected by increased BLL in workers of lead-acid battery manufacturing process is that of the "attention and perception" (SDST).

  18. Ability of the new AT1 receptor blocker azilsartan to block angiotensin II-induced AT1 receptor activation after wash-out.

    PubMed

    Miura, Shin-ichiro; Matsuo, Yoshino; Nakayama, Asuka; Tomita, Sayo; Suematsu, Yasunori; Saku, Keijiro

    2014-03-01

    The recently approved angiotensin II (Ang II) type 1 (AT1) receptor blocker (ARB) azilsartan strongly reduces blood pressure (BP) in patients with hypertension. We previously reported that azilsartan showed unique binding behavior to the AT1 receptor because of its 5-oxo-1,2,4-oxadiazole moiety. However, the ability of azilsartan to block Ang II-dependent AT1 receptor activation is not yet clear. Azilsartan and a derivative of azilsartan (azilsartan-7H) that lacks a carboxyl group at the benzimidazole ring were used. Ang II-induced inositol phosphate (IP) production and extracellular signal-regulated kinase (ERK) activation were analyzed in a cell-based wash-out assay. Azilsartan, but not azilsartan-7H, completely blocked Ang II-induced IP production and ERK activation. Our previous report demonstrated that azilsartan mainly interacts with Tyr(113), Lys(199), and Gln(257) in the AT1 receptor. The interactions between azilsartan and Tyr(113) and Gln(257), but not Lys(199), were critical for blocking Ang II-induced IP production and ERK activation after wash-out. Although our findings regarding the molecule-specific effects of azilsartan are based on basic research, they may lead to an exciting insight into the mechanism of azilsartan.

  19. Hormesis and the Salk Polio Vaccine

    PubMed Central

    Calabrese, Edward J.

    2011-01-01

    The production of the Salk vaccine polio virus by monkey kidney cells was generated using the synthetic tissue culture medium, Mixture 199. In this paper’s retrospective assessment of this process, it was discovered that Mixture 199 was modified by the addition of ethanol to optimize animal cell survival based on experimentation that revealed a hormetic-like biphasic response relationship. This hormesis-based optimization procedure was then applied to all uses of Mixture 199 and modifications of it, including its application to the Salk polio vaccine during preliminary testing and in its subsequent major societal treatment programs. PMID:22423232

  20. Ca 125 and Ca 19-9: two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk.

    PubMed

    Hanisch, F G; Uhlenbruck, G; Dienst, C; Stottrop, M; Hippauf, E

    1985-06-03

    The cancer-associated antigens Ca 125 and Ca 19-9 were demonstrated by radioimmunoassay to form structural units of a mucus glycoprotein in human milk taken from healthy women four days after parturition. The glycoprotein precipitated with the casein fraction at pH 4.6 and was completely absent in the whey as judged from Ca 19-9 assay. It could be effectively enriched by phenol-saline extraction from soluble milk proteins and further purified by gel filtration on Sephacryl S300 and Sephacryl S400. The active component with a bouyant density of 1.41 g/ml in isopycnic density gradient centrifugation (CsCl) shared common physico-chemical and chemical characteristics of mucus glycoproteins. Carbohydrates representing about 68% by weight were conjugated to protein by alkali-labile linkages, exclusively and were essentially free of D-mannose. Activities of Ca 125 and Ca 19-9 were both destroyed by treatment with periodate, mild alkali or neuraminidase suggesting the antigens are sialylated saccharides bound to protein by alkali-labile linkages. The fraction of monosialylated saccharide alditols isolated after reductive beta-elimination from the mucus glycoprotein was shown to inhibit monoclonal antibodies anti-(Ca 125) and anti-(Ca 19-9) in radioimmunoassay.

  1. Expression profile of endothelin receptors (ETA and ETB) and microRNAs-155 and -199 in the corpus cavernosum of rats submitted to chronic alcoholism and diabetes mellitus.

    PubMed

    Gonçalves, F Z; Lizarte Neto, F S; Novais, P C; Gattas, D; Lourenço, L G; de Carvalho, C A M; Tirapelli, D P C; Molina, C A F; Tirapelli, L F; Tucci, S

    2018-03-01

    Recent evidence shows that chronic ethanol consumption increases endothelin (ET)-1 induced sustained contraction of trabecular smooth muscle cells of the corpora cavernosa in corpus cavernosum of rats by a mechanism that involves increased expression of ETA and ETB receptors. Our goal was to evaluate the effects of alcohol and diabetes and their relationship to miRNA-155, miRNA-199 and endothelin receptors in the corpus cavernosum and blood of rats submitted to the experimental model of diabetes mellitus and chronic alcoholism. Forty-eight male Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D), and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study the protein expression of endothelin receptors by immunohistochemistry and expression of miRNAs-155 and -199 in serum and the cavernous tissue. Immunostaining for endothelin receptors was markedly higher in the A, D, and AD groups than in the C group. Moreover, a significant hypoexpression of the miRNA-199 in the corpus cavernosum tissue from the AD group was observed, compared to the C group. When analyzing the microRNA profile in blood, a significant hypoexpression of miRNA-155 in the AD group was observed compared to the C group. The miRNA-199 analysis demonstrated significant hypoexpression in D and AD groups compared to the C group. Our findings in corpus cavernosum showed downregulated miRNA-155 and miRNA-199 levels associated with upregulated protein expression and unaltered mRNA expression of ET receptors suggesting decreased ET receptor turnover, which can contribute to erectile dysfunction in diabetic rats exposed to high alcohol levels.

  2. Biotechnological Production of Caffeic Acid by Bacterial Cytochrome P450 CYP199A2

    PubMed Central

    Arai, Yuka; Kino, Kuniki

    2012-01-01

    Caffeic acid is a biologically active molecule that has various beneficial properties, including antioxidant, anticancer, and anti-inflammatory activities. In this study, we explored the catalytic potential of a bacterial cytochrome P450, CYP199A2, for the biotechnological production of caffeic acid. When the CYP199A2 enzyme was reacted with p-coumaric acid, it stoichiometrically produced caffeic acid. The crystal structure of CYP199A2 shows that Phe at position 185 is situated directly above, and only 6.35 Å from, the heme iron. This F185 residue was replaced with hydrophobic or hydroxylated amino acids using site-directed mutagenesis to create mutants with novel and improved catalytic properties. In whole-cell assays with the known substrate of CYP199A2, 2-naphthoic acid, only the wild-type enzyme hydroxylated 2-naphthoic acid at the C-7 and C-8 positions, whereas all of the active F185 mutants exhibited a preference for C-5 hydroxylation. Interestingly, several F185 mutants (F185V, F185L, F185I, F185G, and F185A mutants) also acquired the ability to hydroxylate cinnamic acid, which was not hydroxylated by the wild-type enzyme. These results demonstrate that F185 is an important residue that controls the regioselectivity and the substrate specificity of CYP199A2. Furthermore, Escherichia coli cells expressing the F185L mutant exhibited 5.5 times higher hydroxylation activity for p-coumaric acid than those expressing the wild-type enzyme. By using the F185L whole-cell catalyst, the production of caffeic acid reached 15 mM (2.8 g/liter), which is the highest level so far attained in biotechnological production of this compound. PMID:22729547

  3. Neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1, and carbohydrate antigen 19-9 in pancreatic juice: pathobiologic implications in diagnosing benign and malignant disease of the pancreas.

    PubMed

    Kaur, Sukhwinder; Baine, Michael J; Guha, Sushovan; Ochi, Nobuo; Chakraborty, Subhankar; Mallya, Kavita; Thomas, Colleen; Crook, Julia; Wallace, Michael B; Woodward, Timothy A; Jain, Maneesh; Singh, Shailender; Sasson, Aaron R; Skinner, Verna; Raimondo, Massimo; Batra, Surinder K

    2013-04-01

    Pancreatic diseases pose significant diagnostic challenge as signs and symptoms often overlap. We investigated the potential of pancreatic juice neutrophil gelatinase-associated lipocalin, macrophage inhibitory cytokine 1 (MIC-1), and carbohydrate antigen 19-9 (CA19-9) to aid in the diagnosis of patients with symptoms suggestive of pancreatic diseases. A total of 105 chronic pancreatitis (CP), pancreatic cancer (PC), and nonpancreatic nonhealthy (patients with symptoms mimicking pancreatic disease but found to be free of any pancreatic disease) patients underwent endoscopic pancreatic juice collection after secretin stimulation. Neutrophil gelatinase-associated lipocalin and MIC-1 levels were measured by enzyme-linked immunosorbent assay, whereas CA19-9 was measured by radioimmunoassay. Neutrophil gelatinase-associated lipocalin, MIC-1, and CA19-9 were significantly elevated in the pancreatic juice of patients with CP and patients with PC as compared with nonpancreatic nonhealthy controls (P ≤ 0.034). Neutrophil gelatinase-associated lipocalin seemed most promising in differentiating diseased versus nondiseased pancreata (areas under the curve, 0.88-0.91), whereas MIC-1 was found to be higher in patients with PC than in patients with CP (P = 0.043). Interestingly, MIC-1 levels in diabetic patients with PC were higher than in nondiabetic patients with PC (P = 0.030) and diabetic patients with CP (P = 0.087). Carbohydrate antigen 19-9 showed the least ability to distinguish patient groups (areas under the curve, 0.61-0.76). Pancreatic juice neutrophil gelatinase-associated lipocalin shows potential utility in establishing pancreatic etiology in the context of nonspecific symptoms, whereas MIC-1 may aid in differentiating PC from CP.

  4. 32 CFR 199.25 - TRICARE Retired Reserve.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.25 TRICARE Retired Reserve. (a) Establishment. TRICARE Retired Reserve is established for the purpose of offering the medical... requirements of this section, if permitted by law, based on extraordinary circumstances. (g) Terminology. The...

  5. 32 CFR 199.25 - TRICARE Retired Reserve.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.25 TRICARE Retired Reserve. (a) Establishment. TRICARE Retired Reserve is established for the purpose of offering the medical... requirements of this section, if permitted by law, based on extraordinary circumstances. (g) Terminology. The...

  6. 32 CFR 199.25 - TRICARE Retired Reserve.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.25 TRICARE Retired Reserve. (a) Establishment. TRICARE Retired Reserve is established for the purpose of offering the medical... requirements of this section, if permitted by law, based on extraordinary circumstances. (g) Terminology. The...

  7. 32 CFR 199.25 - TRICARE Retired Reserve.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.25 TRICARE Retired Reserve. (a) Establishment. TRICARE Retired Reserve is established for the purpose of offering the medical... requirements of this section, if permitted by law, based on extraordinary circumstances. (g) Terminology. The...

  8. 38. LANDSCAPE HIGHWAY VIEW, OREGON STATE HIGHWAY 199. JOSPHINE COUNTY, ...

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

    38. LANDSCAPE HIGHWAY VIEW, OREGON STATE HIGHWAY 199. JOSPHINE COUNTY, OREGON. REEVES CREEK (WHERE ROAD WIDENS) 4 MILES NE OF CAVE JUNCTION. LOOKING S. - Redwood National & State Parks Roads, California coast from Crescent City to Trinidad, Crescent City, Del Norte County, CA

  9. A trapped mercury 199 ion frequency standard

    NASA Technical Reports Server (NTRS)

    Cutler, L. S.; Giffard, R. P.; Mcguire, M. D.

    1982-01-01

    Mercury 199 ions confined in an RF quadrupole trap and optically pumped by mercury 202 ion resonance light are investigated as the basis for a high performance frequency standard with commercial possibilities. Results achieved and estimates of the potential performance of such a standard are given.

  10. 32 CFR 199.23 - Special Supplemental Food Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... health care during critical times of growth and development, in order to prevent the occurrence of health..., integrated health care network. (26) Supplemental foods. Foods containing nutrients determined by nutritional... (CONTINUED) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.23...

  11. 32 CFR 199.23 - Special Supplemental Food Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... health care during critical times of growth and development, in order to prevent the occurrence of health..., integrated health care network. (26) Supplemental foods. Foods containing nutrients determined by nutritional... (CONTINUED) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.23...

  12. 32 CFR 199.23 - Special Supplemental Food Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... health care during critical times of growth and development, in order to prevent the occurrence of health..., integrated health care network. (26) Supplemental foods. Foods containing nutrients determined by nutritional... (CONTINUED) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.23...

  13. 32 CFR 199.23 - Special Supplemental Food Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... health care during critical times of growth and development, in order to prevent the occurrence of health..., integrated health care network. (26) Supplemental foods. Foods containing nutrients determined by nutritional... (CONTINUED) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.23...

  14. 49 CFR 199.227 - Retention of records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Prevention Program § 199.227 Retention of records. (a) General requirement. Each operator shall maintain records of its alcohol misuse prevention program as provided in this section. The records shall be... pertaining to a determination by a substance abuse professional concerning a covered employee's need for...

  15. 49 CFR 199.227 - Retention of records.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Prevention Program § 199.227 Retention of records. (a) General requirement. Each operator shall maintain records of its alcohol misuse prevention program as provided in this section. The records shall be... pertaining to a determination by a substance abuse professional concerning a covered employee's need for...

  16. 49 CFR 199.227 - Retention of records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Prevention Program § 199.227 Retention of records. (a) General requirement. Each operator shall maintain records of its alcohol misuse prevention program as provided in this section. The records shall be... pertaining to a determination by a substance abuse professional concerning a covered employee's need for...

  17. 49 CFR 199.227 - Retention of records.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Prevention Program § 199.227 Retention of records. (a) General requirement. Each operator shall maintain records of its alcohol misuse prevention program as provided in this section. The records shall be... pertaining to a determination by a substance abuse professional concerning a covered employee's need for...

  18. 49 CFR 199.227 - Retention of records.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Prevention Program § 199.227 Retention of records. (a) General requirement. Each operator shall maintain records of its alcohol misuse prevention program as provided in this section. The records shall be... pertaining to a determination by a substance abuse professional concerning a covered employee's need for...

  19. Role of glutamate-199 in the aging of cholinesterase. (Reannouncement with new availability information)

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

    Saxena, A.; Doctor, B.P.; Maxwell, D.M.

    1993-11-30

    Aging of organophosphate-conjugated acetylcholinesterase results from the loss of an alkoxy group with concomitant stabilization of the conjugate to spontaneous or nucleophile-induced deacylation. We have examined the kinetics of aging in a pinacolylmethylphosphonofluoridate (soman)-inhibited mutant enzyme in which the glutamate (E199) located at the amino-terminal to the active-site sense (S200) was converted to glutamine (Q). For wild type enzyme, the soman-acetylcholinesterase conjugate aged immediately, giving rise to a form of enzyme resistant to reactivation by oximes. In contrast, the E199Q mutant enzyme was largely resistant to aging and could be reactivated by oximes. Since the pH dependence for aging wasmore » not altered appreciably, the primary influence of the loss of charge appears to be on the intrinsic rate of aging. The negative charge on E199 likely imparts an inductive effect on the conjugated organophosphate to facilitate removal of the alkoxy group. Cholinesterases, Aging, Organophosphate.« less

  20. Isotopic study of mercury sources and transfer between a freshwater lake and adjacent forest food web.

    PubMed

    Kwon, Sae Yun; Blum, Joel D; Nadelhoffer, Knute J; Timothy Dvonch, J; Tsui, Martin Tsz-Ki

    2015-11-01

    Studies of monomethylmercury (MMHg) sources and biogeochemical pathways have been extensive in aquatic ecosystems, but limited in forest ecosystems. Increasing evidence suggests that there is significant mercury (Hg) exchange between aquatic and forest ecosystems. We use Hg stable isotope ratios (δ(202)Hg and Δ(199)Hg) to investigate the relative importance of MMHg sources and assess Hg transfer pathways between Douglas Lake and adjacent forests located at the University of Michigan Biological Station, USA. We characterize Hg isotopic compositions of basal resources and use linear regression of % MMHg versus δ(202)Hg and Δ(199)Hg to estimate Hg isotope values for inorganic mercury (IHg) and MMHg in the aquatic and adjacent forest food webs. In the aquatic ecosystem, we found that lake sediment represents a mixture of IHg pools deposited via watershed runoff and precipitation. The δ(202)Hg and Δ(199)Hg values estimated for IHg are consistent with other studies that measured forest floor in temperate forests. The Δ(199)Hg value estimated for MMHg in the aquatic food web indicates that MMHg is subjected to ~20% photochemical degradation prior to bioaccumulation. In the forest ecosystem, we found a significant negative relationship between total Hg and δ(202)Hg and Δ(199)Hg of soil collected at multiple distances from the lakeshore and lake sediment. This suggests that IHg input from watershed runoff provides an important Hg transfer pathway between the forest and aquatic ecosystems. We measured Δ(199)Hg values for high trophic level insects and compared these insects at multiple distances perpendicular to the lake shoreline. The Δ(199)Hg values correspond to the % canopy cover suggesting that forest MMHg is subjected to varying extents of photochemical degradation and the extent may be controlled by sunlight. Our study demonstrates that the use of Hg isotopes adds important new insight into the relative importance of MMHg sources and complex Hg transfer pathways across ecosystem boundaries. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Comparison of platelet-lymphocyte ratio and CA 19-9 in differentiating benign from malignant head masses in patients with chronic pancreatitis.

    PubMed

    Kakkat, Shanavas; Rajan, Ramesh; Sindhu, R S; Natesh, Bonny; Raviram, S

    2017-07-01

    Pancreatic head ductal adenocarcinoma (PDAC) and inflammatory head masses (IHM) related to chronic pancreatitis are often difficult to differentiate. PDAC produces significant inflammatory response with resultant lymphopenia and thrombocytosis. The prognostic role of platelet-lymphocyte ratio (PLR) as a tumor marker has been defined. We aimed to find the role of PLR as a diagnostic marker for PDAC in differentiating benign head mass comparing with carbohydrate antigen 19-9 (CA 19-9). A prospective study of patients with biopsy-proven PDAC and benign IHM with underlying chronic pancreatitis from 1st November 2014 to 30th June 2016 was performed. Total blood count including platelet count and CA 19-9 were recorded and statistically analyzed. There was no significant difference in total leukocyte counts (7789±2027 vs. 7568±1289 cells/mm 3 ) between PDAC (n = 34) and IHM (n = 27). However, the mean lymphocyte (2235±837 vs. 2701±631 cells/mm 3 ) and platelet counts in mm 3 (3.36±0.789) × 10 5 vs. (2.45±0.598) × 10 5 showed difference. The median PLR was 161.9 (IQR = 117.5-205.6) in PDAC and 91 (IQR = 77.2-106.6) in IHM. The median CA 19-9 (U/mL) in PDAC and IHM was 69.3 (IQR = 22.7-427.7) and 13.9 (IQR = 7.2-23.6), respectively. On plotting the receiver operator characteristic curve (ROC curve), area under the curve was maximum for PLR (88.7%) compared to CA 19-9 (77.8%) in diagnosing PDAC (p<0.0001). Using coordinates of ROC, PLR cutoff value was 113.5 (sensitivity-79.4%, specificity-92.6%, positive predictive value (PPV)-91.5%, negative predictive value (NPV)-99.7%) while CA 19-9 cutoff value was 25.3 U/mL (sensitivity-73.5%, specificity-77.8%, PPV-78.5%, NPV-74.6%). PLR may be useful to differentiate PDAC from benign IHM in patients with chronic pancreatitis.

  2. ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development.

    PubMed

    Cang, Shundong; Iragavarapu, Chaitanya; Savooji, John; Song, Yongping; Liu, Delong

    2015-11-20

    With the advent of new agents targeting CD20, Bruton's tyrosine kinase, and phosphoinositol-3 kinase for chronic lymphoid leukemia (CLL), more treatment options exist than ever before. B-cell lymphoma-2 (BCL-2) plays a major role in cellular apoptosis and is a druggable target. Small molecule inhibitors of BCL-2 are in active clinical studies. ABT-199 (venetoclax, RG7601, GDC-0199) has been granted breakthrough designation by FDA for relapsed or refractory CLL with 17p deletion. In this review, we summarized the latest clinical development of ABT-199/venetoclax and other novel agents targeting the BCL-2 proteins.

  3. Nanocrystalline NiNd0.01Fe1.99O4 as a gas sensor

    NASA Astrophysics Data System (ADS)

    Shinde, Tukaram J.; Gadkari, Ashok B.; Jadhav, Sarjerao R.; Kumar, Surender; Dalawai, Sanjeev P.; Vasambekar, Pramod N.

    2015-06-01

    Nanocrystalline NiNd0.01Fe1.99O4 has been synthesized by oxalate co-precipitation method and was characterized by X-ray diffraction technique. X-ray diffraction analysis confirms the formation of single phase cubic spinel structure. Crystallite size of the ferrite lies in the nano-particle range. The gas sensing properties of nanocrystalline ferrite were studied for gases like Cl2, LPG and C2H5OH. It was observed that NiNd0.01Fe1.99O4 is more sensitive towards chlorine followed by LPG at an operating temperature 277 °C compared to ethanol.

  4. 32 CFR 199.26 - TRICARE Young Adult.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.26 TRICARE Young Adult. (a) Establishment. The TRICARE Young Adult (TYA) program offers the medical benefits provided... sponsors who do not otherwise have eligibility for medical coverage under a TRICARE Program at age 21 (23...

  5. 32 CFR 199.26 - TRICARE Young Adult.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) MISCELLANEOUS CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.26 TRICARE Young Adult. (a) Establishment. The TRICARE Young Adult (TYA) program offers the medical benefits provided... sponsors who do not otherwise have eligibility for medical coverage under a TRICARE Program at age 21 (23...

  6. 49 CFR 199.113 - Employee assistance program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.113 Employee assistance program. (a) Each operator shall provide an employee... must be drug tested based on reasonable cause. The operator may establish the EAP as a part of its...

  7. 49 CFR 199.113 - Employee assistance program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.113 Employee assistance program. (a) Each operator shall provide an employee... must be drug tested based on reasonable cause. The operator may establish the EAP as a part of its...

  8. 49 CFR 199.113 - Employee assistance program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.113 Employee assistance program. (a) Each operator shall provide an employee... must be drug tested based on reasonable cause. The operator may establish the EAP as a part of its...

  9. 49 CFR 199.113 - Employee assistance program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.113 Employee assistance program. (a) Each operator shall provide an employee... must be drug tested based on reasonable cause. The operator may establish the EAP as a part of its...

  10. 49 CFR 199.113 - Employee assistance program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Drug Testing § 199.113 Employee assistance program. (a) Each operator shall provide an employee... must be drug tested based on reasonable cause. The operator may establish the EAP as a part of its...

  11. TPS, CA 19-9, VEGF-A, and CEA as diagnostic and prognostic factors in patients with mass lesions in the pancreatic head.

    PubMed

    Sandblom, Gabriel; Granroth, Sofie; Rasmussen, Ib Christian

    2008-01-01

    Although numerous tumour markers are available for periampullary tumours, including pancreatic cancer, their specificity and sensitivity have been questioned. To assess the diagnostic and prognostic values of tissue polypeptide specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor (VEGF-A), and carcinoembryonic antigen (CEA) we took serum samples in 56 patients with mass lesions in the pancreatic head. Among these patients, further investigations revealed pancreatic cancer in 20 patients, other malignant diseases in 12 and benign conditions in 24. Median CEA in all patients was 3.4 microg/L (range 0.5-585.0), median CA 19-9 was105 kU/L (range 0.6-1 300 00), median TPS 123.5 U/L (range 15.0-3350) and median VEGF-A 132.5 ng/L (range 60.0-4317). Area under the curve was 0.747, standard error (standard error [SE] =0.075) for CEA, 0.716 (SE=0.078) for CA 19-9 and 0.822 (SE=0.086) for TPS in ROC plots based on the ability of the tumours to distinguish between benign and malignant conditions. None of the markers significantly predicted survival in the subgroup of patients with pancreatic cancer. Our study shows that the markers may be used as fairly reliable diagnostic tools, but cannot be used to predict survival.

  12. Poly-L-lysine/hydroxyapatite/carbon nanotube hybrid nanocomposite applied for piezoelectric immunoassay of carbohydrate antigen 19-9.

    PubMed

    Ding, Yanjun; Liu, Jia; Jin, Xiaoyong; Lu, Haixia; Shen, Guoli; Yu, Ruqin

    2008-02-01

    Hybrid composites are of special scientific interest for biochemical applications wherein the abilities to modulate the morphology and property of the hybrid material are important. In this paper, the formation of poly-L-lysine/hydroxyapatite/carbon nanotube (PLL/HA/CNT) hybrid nanoparticles is described and a general design strategy for an immunosensing platform has been proposed on the basis of PLL/HA/CNT nanocomposite adsorption of antibodies. Quartz crystal microbalance (QCM) used as a model transducer and the detection performances of the resulting immunosensor were investigated by use of the immuno-system of carbohydrate antigen 19-9 (CA19-9), an important indicator in the diagnosis of clinical cancers. The hybrid nanocomposite was characterized by the transmission electron microscope (TEM), scanning electron microscope (SEM) and Fourier transform-infrared (FT-IR) spectrum measurements. The frequency response characteristics for the processes of immobilization and immunoreaction of anchored anti-CA19-9 antibodies were studied in detail. It was found that the developed sensing interface has some advantages such as the activation-free immobilization and the high antigen-binding activities of antibodies. The as-prepared immunosensor can allow for the determination of CA19-9 in the concentration range of around 12.5-270.0 U ml(-1). Such an interface design with the hybrid nanocomposite should be tailored as a new alternative used for biosensor design.

  13. ICP22 and the UL13 Protein Kinase Are both Required for Herpes Simplex Virus-Induced Modification of the Large Subunit of RNA Polymerase II

    PubMed Central

    Long, Melissa C.; Leong, Vivian; Schaffer, Priscilla A.; Spencer, Charlotte A.; Rice, Stephen A.

    1999-01-01

    Herpes simplex virus type 1 (HSV-1) infection alters the phosphorylation of the large subunit of RNA polymerase II (RNAP II), resulting in the depletion of the hypophosphorylated and hyperphosphorylated forms of this polypeptide (known as IIa and IIo, respectively) and induction of a novel, alternatively phosphorylated form (designated IIi). We previously showed that the HSV-1 immediate-early protein ICP22 is involved in this phenomenon, since induction of IIi and depletion of IIa are deficient in cells infected with 22/n199, an HSV-1 ICP22 nonsense mutant (S. A. Rice, M. C. Long, V. Lam, P. A. Schaffer, and C. A. Spencer, J. Virol. 69:5550–5559, 1995). However, depletion of IIo still occurs in 22/n199-infected cells. This suggests either that another viral gene product affects the RNAP II large subunit or that the truncated ICP22 polypeptide encoded by 22/n199 retains residual activity which leads to IIo depletion. To distinguish between these possibilities, we engineered an HSV-1 ICP22 null mutant, d22-lacZ, and compared it to 22/n199. The two mutants are indistinguishable in their effects on the RNAP II large subunit, suggesting that an additional viral gene product is involved in altering RNAP II. Two candidates are UL13, a protein kinase which has been implicated in ICP22 phosphorylation, and the virion host shutoff (Vhs) factor, the expression of which is positively regulated by ICP22 and UL13. To test whether UL13 is involved, a UL13-deficient viral mutant, d13-lacZ, was engineered. This mutant was defective in IIi induction and IIa depletion, displaying a phenotype very similar to that of d22-lacZ. In contrast, a Vhs mutant had effects that were indistinguishable from wild-type HSV-1. Therefore, UL13 but not the Vhs function plays a role in modifying the RNAP II large subunit. To study the potential role of UL13 in viral transcription, we carried out nuclear run-on transcription analyses in infected human embryonic lung cells. Infections with either UL13 or ICP22 mutants led to significantly reduced amounts of viral genome transcription at late times after infection. Together, our results suggest that ICP22 and UL13 are involved in a common pathway that alters RNAP II phosphorylation and that in some cell lines this change promotes viral late transcription. PMID:10364308

  14. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    PubMed

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses cholinesterases to increase cholinergic signaling, resulting in decreased expression of proinflammatory cytokines. ARC treatment confers protection for SH-SY5Y cells through positive regulation of miRNA expression, thereby reducing the inflammatory response. In turn, these effects accelerate injury repair in the scratch-induced injury model. These results might provide insights into the pharmacological role of ARC in anti-inflammation and neuroprotection in neural cells.

  15. 199. Photocopy of drawing (1976 structural drawing by the Space ...

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

    199. Photocopy of drawing (1976 structural drawing by the Space and Missile Test Center, VAFB, USAF) STRUCTURAL DETAILS FOR THE MST STAND-TALKERS SHELTER, SHEET S24 - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 East, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  16. 32 CFR 199.12 - Third party recoveries.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of § 199.10 of this part. However, the proper exercise of the right to appeal benefit or provider... to the injury or disease for which care and treatment are being given and concerning any action... additional information concerning the circumstances of the injury or disease and/or the identify of any...

  17. 77 FR 10666 - Pipeline Safety: Post Accident Drug and Alcohol Testing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... operators of Liquefied Natural Gas (LNG) facilities to conduct post- accident drug and alcohol tests of... reviewed, along with other applicable sections of Part 199: Under Sec. 199.105, post-accident drug tests of... administering the test. Covered employees must remain available for post-accident testing, but emergency...

  18. 46 CFR 199.280 - Survival craft embarkation and launching arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft embarkation and launching arrangements... Cargo Vessels § 199.280 Survival craft embarkation and launching arrangements. (a) Each lifeboat must be.... (d) All survival craft required for abandonment by the total number of persons on board must be...

  19. 46 CFR 199.245 - Survival craft embarkation and launching arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft embarkation and launching arrangements... Passenger Vessels § 199.245 Survival craft embarkation and launching arrangements. (a) Each davit-launched liferaft must be arranged to be rapidly boarded by its full complement of persons. (b) All survival craft...

  20. 30 CFR 19.9 - Performance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MINING PRODUCTS ELECTRIC CAP LAMPS § 19.9 Performance. In addition to the general design and the safety... respect to performance, as follows: (a) Time of burning and candlepower. Permissible electric cap lamps.... The life of a bulb is the number of hours its main filament will burn in the cap lamp or its...

  1. 26 CFR 1.199-0 - Table of contents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... receipts. (1) In general. (2) Reasonable method of allocation. (3) De minimis rules. (i) DPGR. (ii) Non... of completion method. (3) Examples. § 1.199-2Wage limitation. (a) Rules of application. (1) In... reported on return filed with the Social Security Administration. (i) In general. (ii) Corrected return...

  2. 32 CFR 199.22 - TRICARE Retiree Dental Program (TRDP).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false TRICARE Retiree Dental Program (TRDP). 199.22... TRICARE Retiree Dental Program (TRDP). (a) Purpose. The TRDP is a premium based indemnity dental insurance... and capabilities of the Uniformed Services overseas dental treatment facilities and a particular...

  3. 32 CFR 199.22 - TRICARE Retiree Dental Program (TRDP).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false TRICARE Retiree Dental Program (TRDP). 199.22... TRICARE Retiree Dental Program (TRDP). (a) Purpose. The TRDP is a premium based indemnity dental insurance... and capabilities of the Uniformed Services overseas dental treatment facilities and a particular...

  4. 32 CFR 199.22 - TRICARE Retiree Dental Program (TRDP).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false TRICARE Retiree Dental Program (TRDP). 199.22... TRICARE Retiree Dental Program (TRDP). (a) Purpose. The TRDP is a premium based indemnity dental insurance... and capabilities of the Uniformed Services overseas dental treatment facilities and a particular...

  5. 32 CFR 199.22 - TRICARE Retiree Dental Program (TRDP).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false TRICARE Retiree Dental Program (TRDP). 199.22... TRICARE Retiree Dental Program (TRDP). (a) Purpose. The TRDP is a premium based indemnity dental insurance... and capabilities of the Uniformed Services overseas dental treatment facilities and a particular...

  6. 32 CFR 199.22 - TRICARE Retiree Dental Program (TRDP).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false TRICARE Retiree Dental Program (TRDP). 199.22... TRICARE Retiree Dental Program (TRDP). (a) Purpose. The TRDP is a premium based indemnity dental insurance... and capabilities of the Uniformed Services overseas dental treatment facilities and a particular...

  7. 32 CFR Appendix A to Part 199 - Acronyms

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 199—Acronyms AFR—Air Force Regulation AR—Army Regulation ASD (HA)—Assistant Secretary of Defense... Renal Disease CT—Computerized Tomography DASD (A)—Deputy Assistant Secretary of Defense (Administration....—Licensed Practical Nurse L.V.N.—Licensed Vocational Nurse MBD—Minimal Brain Dysfunction MCO—Marine Corps...

  8. 32 CFR Appendix A to Part 199 - Acronyms

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 199—Acronyms AFR—Air Force Regulation AR—Army Regulation ASD (HA)—Assistant Secretary of Defense... Renal Disease CT—Computerized Tomography DASD (A)—Deputy Assistant Secretary of Defense (Administration....—Licensed Practical Nurse L.V.N.—Licensed Vocational Nurse MBD—Minimal Brain Dysfunction MCO—Marine Corps...

  9. 32 CFR Appendix A to Part 199 - Acronyms

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 199—Acronyms AFR—Air Force Regulation AR—Army Regulation ASD (HA)—Assistant Secretary of Defense... Renal Disease CT—Computerized Tomography DASD (A)—Deputy Assistant Secretary of Defense (Administration....—Licensed Practical Nurse L.V.N.—Licensed Vocational Nurse MBD—Minimal Brain Dysfunction MCO—Marine Corps...

  10. A199, southwest front and southeast side, also showing magazine A210 ...

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

    A-199, southwest front and southeast side, also showing magazine A-210 in left distance, and water tanks 188-A and 188-B in right distance. View to north northwest. - Mare Island Naval Shipyard, Ordnance Warehouse, Plummer Road, south of Corbett Road, Vallejo, Solano County, CA

  11. 46 CFR 199.203 - Marshalling of liferafts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Additional Requirements for Passenger Vessels § 199.203 Marshalling of liferafts. (a) Each passenger vessel must have a lifeboat or rescue boat for each six liferafts when— (1) Each lifeboat and rescue boat is loaded with its full complement of persons; and (2) The...

  12. 46 CFR 199.176 - Markings on lifesaving appliances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.176 Markings on lifesaving appliances. (a) Lifeboats and rescue boats. Each lifeboat and rescue boat must be plainly marked as follows: (1) Each side of each lifeboat and rescue boat bow must be marked in block...

  13. 46 CFR 199.145 - Marine evacuation system launching arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Marine evacuation system launching arrangements. 199.145....145 Marine evacuation system launching arrangements. (a) Arrangements. Each marine evacuation system... from the marine evacuation system platform by a person either in the liferaft or on the platform; (4...

  14. 46 CFR 199.145 - Marine evacuation system launching arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Marine evacuation system launching arrangements. 199.145....145 Marine evacuation system launching arrangements. (a) Arrangements. Each marine evacuation system... from the marine evacuation system platform by a person either in the liferaft or on the platform; (4...

  15. 46 CFR 199.145 - Marine evacuation system launching arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Marine evacuation system launching arrangements. 199.145....145 Marine evacuation system launching arrangements. (a) Arrangements. Each marine evacuation system... from the marine evacuation system platform by a person either in the liferaft or on the platform; (4...

  16. 46 CFR 199.145 - Marine evacuation system launching arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Marine evacuation system launching arrangements. 199.145....145 Marine evacuation system launching arrangements. (a) Arrangements. Each marine evacuation system... from the marine evacuation system platform by a person either in the liferaft or on the platform; (4...

  17. 46 CFR 199.145 - Marine evacuation system launching arrangements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Marine evacuation system launching arrangements. 199.145....145 Marine evacuation system launching arrangements. (a) Arrangements. Each marine evacuation system... from the marine evacuation system platform by a person either in the liferaft or on the platform; (4...

  18. 19 CFR 19.9 - General order, abandoned, and seized merchandise.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false General order, abandoned, and seized merchandise... Provisions § 19.9 General order, abandoned, and seized merchandise. (a) Acceptance of merchandise. The... storing. General order, abandoned, and seized goods and articles shall be recorded and stored in the...

  19. 19 CFR 19.9 - General order, abandoned, and seized merchandise.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false General order, abandoned, and seized merchandise... Provisions § 19.9 General order, abandoned, and seized merchandise. (a) Acceptance of merchandise. The... storing. General order, abandoned, and seized goods and articles shall be recorded and stored in the...

  20. Facts & Figures on 199 Colleges & Universities for American Indian Students.

    ERIC Educational Resources Information Center

    Winds of Change, 1999

    1999-01-01

    Provides statistical data on 199 colleges that have an American Indian community to provide student support and that graduate a good percentage of their Indian undergraduates. Includes enrollment; affiliations; costs; data on all students, faculty, and entering freshmen; data on Indian students and graduates; and financial, academic, and support…

  1. 40 CFR 264.199 - Special requirements for incompatible wastes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Tank Systems § 264.199 Special requirements for incompatible wastes. (a) Incompatible...(b) is complied with. (b) Hazardous waste must not be placed in a tank system that has not been...

  2. 46 CFR 199.10 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... located. Other regulations may also apply. 3 Not including vessels solely navigating the Great Lakes of... (4) Vessels solely navigating the Great Lakes of North America and the River Saint Lawrence as far... number and type of survival craft specified in table 199.630 of this part and cargo vessels in oceans and...

  3. 46 CFR 199.10 - Applicability.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... located. Other regulations may also apply. 3 Not including vessels solely navigating the Great Lakes of... (4) Vessels solely navigating the Great Lakes of North America and the River Saint Lawrence as far... number and type of survival craft specified in table 199.630 of this part and cargo vessels in oceans and...

  4. 46 CFR 199.10 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... located. Other regulations may also apply. 3 Not including vessels solely navigating the Great Lakes of... (4) Vessels solely navigating the Great Lakes of North America and the River Saint Lawrence as far... number and type of survival craft specified in table 199.630 of this part and cargo vessels in oceans and...

  5. 32 CFR 199.5 - TRICARE Extended Care Health Option (ECHO).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... average non-medical person without direct supervision of a health care provider after the primary... maintain, minimize or prevent deterioration of function of an ECHO-eligible dependent. (b) Eligibility. (1.... Respite care for the purpose of covering primary caregiver (as defined in § 199.2) absences due to...

  6. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  7. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  8. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  9. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  10. 46 CFR 199.160 - Rescue boat embarkation, launching and recovery arrangements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Rescue boat embarkation, launching and recovery... Vessels § 199.160 Rescue boat embarkation, launching and recovery arrangements. (a) Each rescue boat must... be used to meet this requirement. (b) Each rescue boat embarkation and launching arrangement must...

  11. An abdominal active can defibrillator may facilitate a successful generator change when a lead failure is present.

    PubMed

    Solomon, A J; Moubarak, J B; Drood, J M; Tracy, C M; Karasik, P E

    1999-10-01

    Defibrillator generator changes are frequently performed on patients with an implantable cardioverter defibrillator in an abdominal pocket. These patients usually have epicardial patches or older endocardial lead systems. At the time of a defibrillator generator change defibrillation may be unsuccessful as a result of lead failure. We tested the hypothesis that an active can defibrillator implanted in the abdominal pocket could replace a non-functioning endocardial lead or epicardial patch. An abdominal defibrillator generator change was performed in 10 patients, (mean age = 67 +/- 13 years, nine men). Initially, a defibrillation threshold (DFT) was obtained using a passive defibrillator and the chronic endocardial or epicardial lead system. DFTs were then performed using an active can emulator and one chronic lead to simulate endocardial or epicardial lead failure. We tested 30 lead configurations (nine endocardial and 21 epicardial). Although a DFT of 7.3 +/- 4.2 joules was obtained with the intact chronic lead system, the active can emulator and one endocardial or epicardial lead still yielded an acceptable DFT of 19.9 +/- 6.1 joules. In addition, a successful implant (DFT < or = 24 joules) could have been accomplished in 28 of 30 (93%) lead configurations. An active can defibrillator in an abdominal pocket may allow for a successful generator change in patients with defibrillator lead malfunction. This would be simpler than abandoning the abdominal implant and moving to a new pectoral device and lead or tunnelling a new endocardial electrode. However, loss of defibrillation capability with a particular complex lead may be a warning of impending loss of other functions (eg. sensing and/or pacing).

  12. Hemothorax with a high carbohydrate antigen 19-9 level caused by a bronchogenic cyst.

    PubMed

    Tsuzuku, Akifumi; Asano, Fumihiro; Murakami, Anri; Masuda, Atsunori; Sobajima, Takuya; Matsuno, Yoshihiko; Matsumoto, Shinsuke; Mori, Yoshio; Takiya, Hiroshi; Iwata, Hitoshi

    2014-01-01

    A 58-year-old man presented with right-sided chest pain. Radiography and computed tomography showed a pleural effusion in the right chest and a mass in the right hilum. Thoracentesis showed a hemothorax. The carbohydrate antigen (CA) 19-9 level in the pleural effusion was very high, requiring differentiation from malignancy. Positron emission tomography showed no significant fluorodeoxy glucose (FDG) accumulation. Magnetic resonance imaging revealed a cystic lesion. The tumor was resected for both a diagnosis and treatment. A pathological examination demonstrated a bronchogenic cyst. An immunohistochemical study suggested that the cyst was the source of the hemothorax and the high CA19-9 level.

  13. 46 CFR 199.620 - Alternatives for all vessels in a specified service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... Vessels operating in oceans; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may... alternative requirement section or paragraph Oceans Coastwise Great Lakes Lakes, bays and sounds Rivers 199.70... lights bearing Coast Guard approval number 161.012/2/1 are not permitted on vessels certificated to...

  14. 46 CFR 199.620 - Alternatives for all vessels in a specified service.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    .... Vessels operating in oceans; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may... alternative requirement section or paragraph Oceans Coastwise Great Lakes Lakes, bays and sounds Rivers 199.70... lights bearing Coast Guard approval number 161.012/2/1 are not permitted on vessels certificated to...

  15. 46 CFR 199.620 - Alternatives for all vessels in a specified service.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... Vessels operating in oceans; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may... alternative requirement section or paragraph Oceans Coastwise Great Lakes Lakes, bays and sounds Rivers 199.70... lights bearing Coast Guard approval number 161.012/2/1 are not permitted on vessels certificated to...

  16. 46 CFR 199.620 - Alternatives for all vessels in a specified service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    .... Vessels operating in oceans; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may... alternative requirement section or paragraph Oceans Coastwise Great Lakes Lakes, bays and sounds Rivers 199.70... lights bearing Coast Guard approval number 161.012/2/1 are not permitted on vessels certificated to...

  17. 46 CFR 199.620 - Alternatives for all vessels in a specified service.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    .... Vessels operating in oceans; coastwise; Great Lakes; lakes, bays, and sounds; and rivers service may... alternative requirement section or paragraph Oceans Coastwise Great Lakes Lakes, bays and sounds Rivers 199.70... lights bearing Coast Guard approval number 161.012/2/1 are not permitted on vessels certificated to...

  18. 32 CFR 199.16 - Supplemental Health Care Program for active duty members.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Supplemental Health Care Program for active duty... (CHAMPUS) § 199.16 Supplemental Health Care Program for active duty members. (a) Purpose and applicability... the supplemental health care program for active duty members of the uniformed services, the provision...

  19. 32 CFR 199.16 - Supplemental Health Care Program for active duty members.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Supplemental Health Care Program for active duty... (CHAMPUS) § 199.16 Supplemental Health Care Program for active duty members. (a) Purpose and applicability... the supplemental health care program for active duty members of the uniformed services, the provision...

  20. 32 CFR 199.16 - Supplemental Health Care Program for active duty members.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Supplemental Health Care Program for active duty... (CHAMPUS) § 199.16 Supplemental Health Care Program for active duty members. (a) Purpose and applicability... the supplemental health care program for active duty members of the uniformed services, the provision...

  1. 32 CFR 199.16 - Supplemental Health Care Program for active duty members.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Supplemental Health Care Program for active duty... (CHAMPUS) § 199.16 Supplemental Health Care Program for active duty members. (a) Purpose and applicability... the supplemental health care program for active duty members of the uniformed services, the provision...

  2. 32 CFR 199.16 - Supplemental Health Care Program for active duty members.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Supplemental Health Care Program for active duty... (CHAMPUS) § 199.16 Supplemental Health Care Program for active duty members. (a) Purpose and applicability... the supplemental health care program for active duty members of the uniformed services, the provision...

  3. 32 CFR 199.26 - TRICARE Young Adult.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for medical coverage under a TRICARE program at age 21 (23 if enrolled in a full-time course of study at an institution of higher learning approved by the Secretary of Defense) and are under age 26. (1... age requirements of § 199.3 of this part, provided that TRICARE Prime is available in the geographic...

  4. 199. Photocopy of photograph, U.S. Army, ca. 1955 (original print ...

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

    199. Photocopy of photograph, U.S. Army, ca. 1955 (original print located at Rocky Mountain Arsenal, Commerce City, Colorado). WORKERS AT GB BOMB PRODUCTION LINE IN BUILDING 1606. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  5. 46 CFR 199.157 - Free-fall lifeboat launching and recovery arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Free-fall lifeboat launching and recovery arrangements... § 199.157 Free-fall lifeboat launching and recovery arrangements. (a) The launching appliance for a free-fall lifeboat must be designed and installed so that the launching appliance and the lifeboat it serves...

  6. 46 CFR 199.157 - Free-fall lifeboat launching and recovery arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Free-fall lifeboat launching and recovery arrangements... § 199.157 Free-fall lifeboat launching and recovery arrangements. (a) The launching appliance for a free-fall lifeboat must be designed and installed so that the launching appliance and the lifeboat it serves...

  7. 46 CFR 199.157 - Free-fall lifeboat launching and recovery arrangements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Free-fall lifeboat launching and recovery arrangements... § 199.157 Free-fall lifeboat launching and recovery arrangements. (a) The launching appliance for a free-fall lifeboat must be designed and installed so that the launching appliance and the lifeboat it serves...

  8. 46 CFR 199.157 - Free-fall lifeboat launching and recovery arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Free-fall lifeboat launching and recovery arrangements... § 199.157 Free-fall lifeboat launching and recovery arrangements. (a) The launching appliance for a free-fall lifeboat must be designed and installed so that the launching appliance and the lifeboat it serves...

  9. 46 CFR 199.157 - Free-fall lifeboat launching and recovery arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Free-fall lifeboat launching and recovery arrangements... § 199.157 Free-fall lifeboat launching and recovery arrangements. (a) The launching appliance for a free-fall lifeboat must be designed and installed so that the launching appliance and the lifeboat it serves...

  10. 46 CFR 199.212 - Lifejackets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... lifejackets for at least 5 percent of the total number of persons on board. These lifejackets must be stowed in conspicuous places on deck or at muster stations. (b) Where lifejackets for persons other than the... stations, any additional lifejackets required by § 199.70(b)(2)(v) for these persons must be stowed in the...

  11. 46 CFR 199.212 - Lifejackets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... lifejackets for at least 5 percent of the total number of persons on board. These lifejackets must be stowed in conspicuous places on deck or at muster stations. (b) Where lifejackets for persons other than the... stations, any additional lifejackets required by § 199.70(b)(2)(v) for these persons must be stowed in the...

  12. 46 CFR 199.212 - Lifejackets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... lifejackets for at least 5 percent of the total number of persons on board. These lifejackets must be stowed in conspicuous places on deck or at muster stations. (b) Where lifejackets for persons other than the... stations, any additional lifejackets required by § 199.70(b)(2)(v) for these persons must be stowed in the...

  13. 46 CFR 199.212 - Lifejackets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... lifejackets for at least 5 percent of the total number of persons on board. These lifejackets must be stowed in conspicuous places on deck or at muster stations. (b) Where lifejackets for persons other than the... stations, any additional lifejackets required by § 199.70(b)(2)(v) for these persons must be stowed in the...

  14. 46 CFR 199.212 - Lifejackets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... lifejackets for at least 5 percent of the total number of persons on board. These lifejackets must be stowed in conspicuous places on deck or at muster stations. (b) Where lifejackets for persons other than the... stations, any additional lifejackets required by § 199.70(b)(2)(v) for these persons must be stowed in the...

  15. 46 CFR 199.220 - Survival craft and rescue boat embarkation arrangements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Survival craft and rescue boat embarkation arrangements... Passenger Vessels § 199.220 Survival craft and rescue boat embarkation arrangements. (a) Survival craft... rescue boat must be able to be boarded and launched directly from the stowed position with the number of...

  16. 46 CFR 199.220 - Survival craft and rescue boat embarkation arrangements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Survival craft and rescue boat embarkation arrangements... Passenger Vessels § 199.220 Survival craft and rescue boat embarkation arrangements. (a) Survival craft... rescue boat must be able to be boarded and launched directly from the stowed position with the number of...

  17. 46 CFR 199.220 - Survival craft and rescue boat embarkation arrangements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Survival craft and rescue boat embarkation arrangements... Passenger Vessels § 199.220 Survival craft and rescue boat embarkation arrangements. (a) Survival craft... rescue boat must be able to be boarded and launched directly from the stowed position with the number of...

  18. 46 CFR 199.220 - Survival craft and rescue boat embarkation arrangements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Survival craft and rescue boat embarkation arrangements... Passenger Vessels § 199.220 Survival craft and rescue boat embarkation arrangements. (a) Survival craft... rescue boat must be able to be boarded and launched directly from the stowed position with the number of...

  19. 46 CFR 199.220 - Survival craft and rescue boat embarkation arrangements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Survival craft and rescue boat embarkation arrangements... Passenger Vessels § 199.220 Survival craft and rescue boat embarkation arrangements. (a) Survival craft... rescue boat must be able to be boarded and launched directly from the stowed position with the number of...

  20. Gold Nanoparticles Doped with (199) Au Atoms and Their Use for Targeted Cancer Imaging by SPECT.

    PubMed

    Zhao, Yongfeng; Pang, Bo; Luehmann, Hannah; Detering, Lisa; Yang, Xuan; Sultan, Deborah; Harpstrite, Scott; Sharma, Vijay; Cutler, Cathy S; Xia, Younan; Liu, Yongjian

    2016-04-20

    Gold nanoparticles have been labeled with various radionuclides and extensively explored for single photon emission computed tomography (SPECT) in the context of cancer diagnosis. The stability of most radiolabels, however, still needs to be improved for accurate detection of cancer biomarkers and thereby monitoring of tumor progression and metastasis. Here, the first synthesis of Au nanoparticles doped with (199)Au atoms for targeted SPECT tumor imaging in a mouse triple negative breast cancer (TNBC) model is reported. By directly incorporating (199)Au atoms into the crystal lattice of each Au nanoparticle, the stability of the radiolabel can be ensured. The synthetic procedure also allows for a precise control over both the radiochemistry and particle size. When conjugated with D-Ala1-peptide T-amide, the Au nanoparticles doped with (199)Au atoms can serve as a C-C chemokine receptor 5 (CCR5)-targeted nanoprobe for the sensitive and specific detection of both TNBC and its metastasis in a mouse tumor model. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Normal and cancer mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR Axis

    PubMed Central

    Celià-Terrassa, Toni; Liu, Daniel; Choudhury, Abrar; Hang, Xiang; Wei, Yong; Zamalloa, Jose; Alfaro-Aco, Raymundo; Chakrabarti, Rumela; Jiang, Yi-Zhou; Koh, Bong Ihn; Smith, Heath; DeCoste, Christina; Li, Jun-Jing; Shao, Zhi-Ming; Kang, Yibin

    2017-01-01

    Tumor-initiating cells (TICs), or cancer stem cells (CSC), possess stem cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells (MaSCs) and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses. Elevated miR-199a expression in stem cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by epithelial and immune cells in the mammary gland. Importantly, the miR-199a-LCOR-IFN axis is activated in poorly differentiated ER− breast tumors, functionally promotes tumor initiation and metastasis, and is associated with poor clinical outcome. Our study therefore reveals a common mechanism shared by normal and malignant stem cells to protect them from suppressive immune cytokine signaling. PMID:28530657

  2. Revisiting HgCl 2: A solution- and solid-state 199Hg NMR and ZORA-DFT computational study

    NASA Astrophysics Data System (ADS)

    Taylor, R. E.; Carver, Colin T.; Larsen, Ross E.; Dmitrenko, Olga; Bai, Shi; Dybowski, C.

    2009-07-01

    The 199Hg chemical-shift tensor of solid HgCl 2 was determined from spectra of polycrystalline materials, using static and magic-angle spinning (MAS) techniques at multiple spinning frequencies and field strengths. The chemical-shift tensor of solid HgCl 2 is axially symmetric ( η = 0) within experimental error. The 199Hg chemical-shift anisotropy (CSA) of HgCl 2 in a frozen solution in dimethylsulfoxide (DMSO) is significantly smaller than that of the solid, implying that the local electronic structure in the solid is different from that of the material in solution. The experimental chemical-shift results (solution and solid state) are compared with those predicted by density functional theory (DFT) calculations using the zeroth-order regular approximation (ZORA) to account for relativistic effects. 199Hg spin-lattice relaxation of HgCl 2 dissolved in DMSO is dominated by a CSA mechanism, but a second contribution to relaxation arises from ligand exchange. Relaxation in the solid state is independent of temperature, suggesting relaxation by paramagnetic impurities or defects.

  3. The ENB 199: an exploration of its effects on A & E nurses' practice.

    PubMed

    Wood, I

    1998-10-01

    In the UK, educational opportunities for Accident and Emergency (A & E) nurses are varied (Smith 1994) but the course most recognized as offering specialized A & E education is the English National Board (ENB) 199 course (A & E Nursing). This article describes a research study in which semi-structured interviews were used to gain a phenomenological perspective on the effects of undertaking the ENB 199 on the clinical practice of A & E nurses. The article discusses the methodology used and gives details of the interview framework adopted. Ethical issues are considered along with data collection and analysis. Findings of the study indicate that nurses who have successfully completed the ENB 199 express feelings of enhanced self-confidence in their ability to deliver high standards of care. The notion of increased confidence was also reflected in what the nurses described as their ability to question and challenge the practice of both nursing and medical colleagues. The paper also highlights findings which relate to specific clinical issues and the benefit of having time away from clinical practice in which to discuss issues important to practising A & E nurses.

  4. CCL5 promotes vascular endothelial growth factor expression and induces angiogenesis by down-regulating miR-199a in human chondrosarcoma cells.

    PubMed

    Liu, Guan-Ting; Huang, Yuan-Li; Tzeng, Huey-En; Tsai, Chun-Hao; Wang, Shih-Wei; Tang, Chih-Hsin

    2015-02-28

    Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis. Angiogenesis is a critical step in tumor growth and metastasis. Chemokine CCL5 (previously called RANTES) has been shown to facilitate tumor progression and metastasis. However, the relationship of CCL5 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma is mostly unknown. In this study, CCL5 increased VEGF expression and also promoted chondrosarcoma medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. MicroRNA analysis was performed in CCL5-treated chondrosarcoma cells versus control cells to investigate the mechanism of CCL5-mediated promotion of chondrosarcoma angiogenesis. Among the miRNAs regulated by CCL5, miR-199a was the most downregulated miRNA after CCL5 treatment. In addition, co-transfection with miR-199a mimic reversed the CCL5-mediated VEGF expression and angiogenesis in vitro and in vivo. Moreover, overexpression of CCL5 increased tumor-associated angiogenesis and tumor growth by downregulating miR-199a in the xenograft tumor angiogenesis model. Taken together, these results demonstrated that CCL5 promotes VEGF-dependent angiogenesis in human chondrosarcoma cells by downregulating miR-199a. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms.

    PubMed

    Xu, Bin; Ding, Wei-Xing; Jin, Da-Yong; Wang, Dan-Song; Lou, Wen-Hui

    2013-03-07

    To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P < 0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.

  6. Development of a novel polystyrene/metal-organic framework-199 electrospun nanofiber adsorbent for thin film microextraction of aldehydes in human urine.

    PubMed

    Liu, Feilong; Xu, Hui

    2017-01-01

    In this work, electrospun polystyrene/metal-organic frameworks-199 (PS/MOF-199) nanofiber film was synthesized and investigated as a novel adsorbent for thin film microextraction (TFME) of aldehydes in human urine. Some properties of the prepared PS/MOF-199 nanofiber film, including morphology, structure, wettability, solvent stability and extraction performance were studied systematically. Porous fibrous structure, large surface area, good stability, strong hydrophobicity and excellent extraction efficiency were obtained for the film. Based on the PS/MOF-199 film, a thin film microextraction-high performance liquid chromatography (TFME-HPLC) method was developed, and the experimental parameters that affected the extraction and desorption were optimized. Under the optimal conditions, the limits of detection (LODs) were in the range of 4.2-17.3nmolL -1 for the analysis of six aldehydes. Good linearity was achieved with correlation coefficients (R 2 ) being lager than 0.9943. Satisfactory recovery (82-112%) and acceptable reproducibility (relative standard deviation: 2.1-13.3%) were also obtained for the method. The developed TFME-HPLC method has been successfully applied to the analysis of aldehyde metabolites in the urine samples of lung cancer patients and healthy people. The method possesses the advantages of simplicity, rapidity, cost-effective, sensitivity and non-invasion, it provides an alternative tool for the determination of aldehydes in complex sample matrices. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Mercury Isotope Study of Sources and Exposure Pathways of Methylmercury in Estuarine Food Webs in the Northeastern U.S.

    PubMed Central

    2015-01-01

    We measured mercury (Hg) isotope ratios in sediments and various estuarine organisms (green crab, blue mussel, killifish, eider) to investigate methylmercury (MMHg) sources and exposure pathways in five Northeast coast (U.S.) estuaries. The mass independent Hg isotopic compositions (MIF; Δ199Hg) of the sediments were linearly correlated with the sediment 1/Hg concentrations (Δ199Hg: r2 = 0.77, p < 0.05), but the mass dependent isotope compositions (MDF; δ202Hg) were not (r2 = 0.26, p = 0.16), reflecting inputs of anthropogenic Hg sources with varying δ202Hg. The estuarine organisms all display positive Δ199Hg values (0.21 to 0.98 ‰) indicating that MMHg is photodegraded to varying degrees (5–12%) prior to entry into the food web. The δ202Hg and Δ199Hg values of most organisms can be explained by a mixture of MMHg and inorganic Hg from sediments. At one contaminated site mussels have anomalously high δ202Hg, indicating exposure to a second pool of MMHg, compared to sediment, crabs and fish. Eiders have similar Δ199Hg as killifish but much higher δ202Hg, suggesting that there is an internal fractionation of δ202Hg in birds. Our study shows that Hg isotopes can be used to identify multiple anthropogenic inorganic Hg and MMHg sources and determine the degree of photodegradation of MMHg in estuarine food webs. PMID:25116221

  8. The Cu-MOF-199/single-walled carbon nanotubes modified electrode for simultaneous determination of hydroquinone and catechol with extended linear ranges and lower detection limits.

    PubMed

    Zhou, Jian; Li, Xi; Yang, Linlin; Yan, Songlin; Wang, Mengmeng; Cheng, Dan; Chen, Qi; Dong, Yulin; Liu, Peng; Cai, Weiquan; Zhang, Chaocan

    2015-10-29

    A novel electrochemical sensor based on Cu-MOF-199 [Cu-MOF-199 = Cu3(BTC)2 (BTC = 1,3,5-benzenetricarboxylicacid)] and SWCNTs (single-walled carbon nanotubes) was fabricated for the simultaneous determination of hydroquinone (HQ) and catechol (CT). The modification procedure was carried out through casting SWCNTs on the bare glassy carbon electrode (GCE) and followed by the electrodeposition of Cu-MOF-199 on the SWCNTs modified electrode. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) were performed to characterize the electrochemical performance and surface characteristics of the as-prepared sensor. The composite electrode exhibited an excellent electrocatalytic activity with increased electrochemical signals towards the oxidation of HQ and CT, owing to the synergistic effect of SWCNTs and Cu-MOF-199. Under the optimized condition, the linear response range were from 0.1 to 1453 μmol L(-1) (RHQ = 0.9999) for HQ and 0.1-1150 μmol L(-1) (RCT = 0.9990) for CT. The detection limits for HQ and CT were as low as 0.08 and 0.1 μmol L(-1), respectively. Moreover, the modified electrode presented the good reproducibility and the excellent anti-interference performance. The analytical performance of the developed sensor for the simultaneous detection of HQ and CT had been evaluated in practical samples with satisfying results. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Nuclear medicine in breast cancer diagnostics: Primary tumor and lymphatic metastasis

    NASA Astrophysics Data System (ADS)

    Sinilkin, I.; Medvedeva, A.; Chernov, V.; Slonimskaya, E.; Zelchan, R.; Bragina, O.

    2017-09-01

    The purpose of the study: to assess the possibility of using nuclear medicine techniques at the stages of diagnosis and treatment of breast cancer. Materials and Methods: The study included 290 patients with breast cancer and 70 patients with benign breast tumors. The study was used as a radiopharmaceutical 99mTc-MIBI, 199Tl for imaging tumors and colloid 99mTc-Aloteh for visualization sentinel lymph nodes (SLN), colloid was injected peritumoral in four points to 80 MBq one day prior to the planned operation. Results: The sensitivity of SPECT using both 99mTc-MIBI and 199Tl for breast cancer detection was shown to be rather high, being 98.5% and 98%, respectively. It should be noted that the sensitivity of SPECT in detection of small tumors (less than 1 cm in diameter) and multicentric tumors was not high irrespective of the radioisotope used (60% and 65% with 99mTc-MIBI and 65% and 59% with 199Tl, respectively). The difference in the sensitivity was found between 99mTc-MIBI and 199T for the detection of regional lymph node metastasis (91% vs 70%). SLN were detected in 31 patients. The most commonly SLN were defined in the axillary region of 96.7%. In 22 (70.9%) patients there was no metastasis SLN. The sensitivity of the method was 91.2%, specificity of 100%. Conclusion: The specificity of SPECT with 199Tl was higher than that with 99mTc-MIBI. The data obtained show that SPECT with 199Tl can be recommended for its use as an additional breast cancer detection method in cases when other imaging techniques and histological findings are not accurate enough. The clinical study of 99mTc-Aloteh, a new radiopharmaceutical agent, has shown that the studied colloid has high uptake level in SLN and can be successfully used for visualization of SLN in patients with breast cancer.

  10. Chronic Arsenic Exposure and Angiogenesis in Human Bronchial Epithelial Cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway

    PubMed Central

    He, Jun; Wang, Min; Jiang, Yue; Chen, Qiudan; Xu, Shaohua; Xu, Qing; Jiang, Bing-Hua

    2014-01-01

    Background: Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood. Objectives: We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth. Methods: We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis. Results: We found that miR-199a-5p expression levels were more than 100-fold lower in arsenic-transformed cells than parental cells. Re-expression of miR-199a-5p impaired arsenic-induced angiogenesis and tumor growth through its direct targets HIF-1α and COX-2. We further showed that arsenic induced COX-2 expression through HIF-1 regulation at the transcriptional level. In addition, we demonstrated that reactive oxygen species are an upstream event of miR-199a-5p/ HIF-1α/COX-2 pathway in arsenic-induced carcinogenesis. Conclusion: The findings establish critical roles of miR-199a-5p and its downstream targets HIF-1/COX-2 in arsenic-induced tumor growth and angiogenesis. Citation: He J, Wang M, Jiang Y, Chen Q, Xu S, Xu Q, Jiang BH, Liu LZ. 2014. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a-5p/HIF-1α/COX-2 Pathway. Environ Health Perspect 122:255–261; http://dx.doi.org/10.1289/ehp.1307545 PMID:24413338

  11. Unexpected distribution of CA19.9 and other type 1 chain Lewis antigens in normal and cancer tissues of colon and pancreas: Importance of the detection method and role of glycosyltransferase regulation.

    PubMed

    Aronica, Adele; Avagliano, Laura; Caretti, Anna; Tosi, Delfina; Bulfamante, Gaetano Pietro; Trinchera, Marco

    2017-01-01

    CA19.9 antigen has been assumed as an abundant product of cancer cells, due to the reactivity found by immunohistochemical staining of cancer tissues with anti-CA19.9 antibody. Expression and biosynthesis of type 1 chain Lewis antigens in the colon and the pancreas were studied by immunodetection in tissue sections and lysates, quantification of glycosyltransferase transcripts, bisulfite sequencing, and chromatin immunoprecipitation assays. CA19.9 was poorly detectable in normal colon mucosa and almost undetectable in colon cancer, while it was easily detected in the pancreatic ducts, together with Lewis b antigen, under both normal and cancer conditions. B3GALT5 transcripts were down-regulated in colon cancer, while they remained expressed in pancreatic cancer. Even ST3GAL3 transcript appeared well expressed in the pancreas but poorly in the colon, irrespective of normal or cancer conditions. CpG islands flanking B3GALT5 native promoter presented an extremely low degree of methylation in pancreatic cancer with respect to colon cancer. In a DNA region about 1kb away from the B3GALT5 retroviral promoter, a stretch of CG dinucleotides presented a methylation pattern potentially associated with transcription. Such a DNA region and the transcription factor binding site provided overlapping results by chromatin immunoprecipitation assays, corroborating the hypothesis. CA19.9 appears as a physiological product whose synthesis strongly depends on the tissue specific and epigenetically-regulated expression of B3GALT5 and ST3GAL3. CA19.9 and other Lewis antigens acquire tumor marker properties in the pancreas due to mechanisms giving rise to reabsorption into vessels and elevation in circulating levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Genetic variants of APOC3 promoter and HLA-B genes in an HIV infected cohort in northern South Africa: a pilot study.

    PubMed

    Masebe, Tracy; Bessong, Pascal Obong; Ndip, Roland Ndip; Meyer, Debra

    2014-06-26

    Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of -482 (p = 1; χ2 = 0.00001) or -455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the -455C genotype, but not in males for the -455T genotype. Viral load decreases were significant with the -455C and -482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders.

  13. Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer.

    PubMed

    Xing, Lingxi; Shi, Qiusheng; Zheng, Kailiang; Shen, Ming; Ma, Jing; Li, Fan; Liu, Yang; Lin, Lizhou; Tu, Wenzhi; Duan, Yourong; Du, Lianfang

    2016-01-01

    Pancreatic cancer, one of the most lethal human malignancies with dismal prognosis, is refractory to existing radio-chemotherapeutic treatment modalities. There is a critical unmet need to develop effective approaches, especially for targeted pancreatic cancer drug delivery. Targeted and drug-loaded nanoparticles (NPs) combined with ultrasound-mediated microbubble destruction (UMMD) have been shown to significantly increase the cellular uptake in vitro and drug retention in vivo, suggesting a promising strategy for cancer therapy. In this study, we synthesized pancreatic cancer-targeting organic NPs that were modified with anti CA19-9 antibody and encapsulated paclitaxol (PTX). The three-block copolymer methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) constituted the skeleton of the NPs. We speculated that the PTX-NPs-anti CA19-9 would circulate long-term in vivo, "actively target" pancreatic cancer cells, and sustainably release the loaded PTX while UMMD would "passively target" the irradiated tumor and effectively increase the permeability of cell membrane and capillary gaps. Our results demonstrated that the combination of PTX-NPs-anti CA19-9 with UMMD achieved a low IC50, significant cell cycle arrest, and cell apoptosis in vitro. In mouse pancreatic tumor xenografts, the combined application of PTX-NP-anti CA19-9 NPs with UMMD attained the highest tumor inhibition rate, promoted the pharmacokinetic profile by increasing AUC, t1/2, and mean residence time (MRT), and decreased clearance. Consequently, the survival of the tumor-bearing nude mice was prolonged without obvious toxicity. The dynamic change in cellular uptake, targeted real-time imaging, and the concentration of PTX in the plasma and tumor were all closely associated with the treatment efficacy both in vitro and in vivo. Our study suggests that PTX-NP-anti CA19-9 NPs combined with UMMD is a promising strategy for the treatment of pancreatic cancer.

  14. Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19-9 and CA 72-4 levels in gastric and colorectal cancer patients.

    PubMed

    Ning, Shufang; Wei, Wene; Li, Jilin; Hou, Bingbing; Zhong, Jianhong; Xie, Yuxuan; Liu, Haizhou; Mo, Xianwei; Chen, Jiansi; Zhang, Litu

    2018-01-01

    Despite extensive progress in treatment for cancer in recent decades, the early diagnosis for gastric cancer (GC) and colorectal cancer (CRC) remains poor. In this study, we explore the diagnostic value of joint detection of thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 72-4 (CA 72-4) in the diagnosis of GC and CRC, and to evaluated the relationship between TK1 expression and clinical pathological characteristics in the patients. Serum TK1, CA 19-9, CA 72-4 and CEA levels were measured in 169 patients with GC, 344 patients with CRC and 75 healthy controls using electro-chemiluminescence. The TK1 concentration was significantly higher in patients with cancer than in healthy controls and patients with clinical stage Ⅲ+Ⅳ had higher TK1 levels than clinical stage Ⅰ+Ⅱ ( P <0.05). The levels of TK1 is significantly associated with tumor stage, lymph node metastasis, distant metastasis, tumor differentiation and age ( P <0.05). When the tumor markers (TK1, CA 19-9 and CA 72-4) were detected respectively, the area under receiver operating characteristics curve (AUC) of TK1 for three cancers was the highest (0.823-0.895). However, the combination of AUC was higher than that for each tumor marker detected respectively (0.934-0.953), and the Hosmer-Lemeshow test showed an adequate model of calibration (P>0.05). Moreover, the AUCs varied significantly between the combination tests and single biomarker tests (Z test, P <0.01). In conclusion, serum TK1 may be an independent tumor marker for GC and CRC patients, and the combination of TK1, CA 19-9 and CA 72-4 and CEA performed even better. This study suggests that combination detection of four tumor markers may prove to be useful for the diagnosis of GC and CRC.

  15. [CEA, CA-19-9 and il-8, sTNFRII and sil-2R in persons at high risk of colorectal cancer].

    PubMed

    Grotowski, Maciej; Wojtuń, Stanisław

    2003-04-01

    The aim of the study was to determine whether elevated concentrations of CEA, CA19-9, IL-8, sTNFRII and sIL-2R occur in persons at high risk of colorectal cancer. A group of 37 persons at high risk of colorectal cancer and 40 healthy subjects (control group) were included into this study. In both groups IL-8, sTNFRII and sIL-2R concentrations were measured by ELISA method (R&D Systems Minneapolis, USA). In the group of persons at high risk of colorectal cancer CEA and CA19-9 concentrations were determined using MEIA kits (Abbott Laboratories, USA). Using the 95th percentiles of the distribution in the control group the upper normal limits of IL-8, sTN-FRII and sIL-2R values were calculated. The cut-off value for CEA was 3 ng/ml and that for CA 19-9 was 37 U/ml. The incidence of elevated concentrations of the studied factors and concentrations of CEA and CA19-9 was compared. The association was assessed of elevated concentrations of the studied factors and CEA and CA19-9 with the results of histological examination of pathological changes in the colon and rectum. In the group of persons at high risk of colorectal cancer only CEA concentration was elevated in 2.7%. The percentages of persons with elevated concentrations of IL-8, sIL-2R and sTNFRII were 29.7, 8.1 and 18.9%, respectively. The percentage of persons with elevated concentrations of IL-8 and sTNFRII was higher in comparison with the percentage of persons with elevated concentrations of CEA and CA19-9 (p < 0.05). Pathological lesions in the colon and rectum were detected in 16 persons (43.2%). High-grade dysplasia was detected in 11 cases. Elevated concentration of IL-8 always accompanied high-grade dysplasia in ulcerative colitis. The concentrations of IL-8 were significantly higher in high-grade dysplasia (23.7 pg/ml, SD +/- 7.53) than in cases of its absence (18.9 pg/ml, SD +/- 3.53) (p < 0.05). The obtained results of preliminary studies with IL-8 in persons at high risk of colorectal cancer require a confirmation in population studies.

  16. Evaluation of the importance of the serum levels of CA-125, CA15-3, CA-19-9, carcinoembryonic antigen and alpha fetoprotein for distinguishing benign and malignant adnexal masses and contribution of different test combinations to diagnostic accuracy.

    PubMed

    Bozkurt, M; Yumru, A E; Aral, I

    2013-01-01

    The aim of this study was to investigate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPPV) of the serum levels of CA-125, CA15-3, CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) in the differentiation of benign and malignant ovarian tumors histopathologically diagnosed in patients and to determine the effects of the different test combinations on diagnostic accuracy. One-hundred sixty-eight patients that had their preoperative CA-125, CA15-3, CA19-9, CEA, AFP levels assessed and that were subsequently surgically treated for adnexal masses, were included in the study. For each tumor markers in these patients with histopathologically-confirmed diagnosis, the sensitivity, specificity, PPV and NPV, and diagnostic accuracy, and odds ratio were calculated. The sensitivity, specificity, PPV, NPV of CA125 with cut-off 35 U/ml, were found to be 78.9%, 86.9%, 63.8%, and 93.3%, respectively. The diagnostic odds ratio of CA-125 with cut-off of 35 U/ml, was found to be 25. With cut-off65 U/ml, the sensitivity, specificity, PPV, NPV values were 65.7%, 95.3%, 80.6%, and 90.5%, respectively. The sensitivity, specificity, PPV, and NPV of CEA were 16%, 93%, 37%, and 83%, respectively. For AFP, the sensitivity, specificity, PPV and NPV were to be 2.6%, 98%, 33.3%, and 77.5%, respectively. For CA 15-3, the sensitivity, specificity, PPV and NPV were found to be 26.3% 96.1%, 66.6%, and 81.6%, respectively. Likelihood ratio tests: positive (LR+) = 6.83 and negative (LR-) = 0.76, with an odds ratio: 8.9. The risk of malignancy for adnexal masses with higher CA15-3 increased by approximately nine times. For CA19-9, the sensitivity, specificity, PPV and NPV value were found to be 18.4%, 93%, 43.7%, and 79.6%, respectively. CA19-9 was not statistically significant in the differentiation of benign and malignant of adnexal masses. Even the combinations of CA125 + CEA + CA19-9 and CA125 + CEA + CA19-9 +AFP and CA125 + CA15-3 made a small contribution (one, two, and four cases, respectively), but was not statistically significant. The levels of CA-125 and CA15-3 were found to be significant in order to distinguish benign and malign; CA 19-9, CEA, and AFP were not found to be significant. The different test combinations did not have contribution for diagnostic accuracy.

  17. End-stage renal disease after occupational lead exposure: 20 years of follow-up.

    PubMed

    Evans, Marie; Discacciati, Andrea; Quershi, Abdul Rashid; Åkesson, Agneta; Elinder, Carl-Gustaf

    2017-06-01

    Whether low-level exposure to lead may give rise to chronic kidney disease or end-stage renal disease (ESRD) is debated. In this study, we aimed to specifically investigate if low-level occupational exposure to lead was associated with increased incidence of ESRD. The incidence of starting renal replacement therapy as a result of ESRD was examined in a cohort of10 303 lead-workers who had controlled blood lead concentrations due to a compulsory occupational health surveillance programme in Sweden during the time period 1977-1990. The ESRD incidence (obtained through register-linkage) among the lead-exposed workers was compared with the age, sex and calendar period-adjusted expected incidence based on data from the Swedish renal registry. Dose-response association was evaluated in external (general population) and internal (within the occupational cohort) comparisons by highest achieved blood lead level. There were 30 (0.29%) individuals in the cohort who developed ESRD during the median follow-up period of 26.3 years. The standardised incidence ratio (SIR) for ESRD incidence was 0.79 (95% CI 0.54 to 1.13). Among those who achieved the highest blood lead (>41.4 µg/dL), the SIR was 1.01 (0.44 to 1.99). There was no evidence of a dose-response relationship between the maximum achieved blood lead or the cumulative blood lead exposure and ESRD in external or internal comparisons. This study of workers with documented occupational lead exposures followed for 20 years shows no statistically significant association between lead exposure (following the current occupational recommendations for Sweden) and ESRD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. 75 FR 44198 - Proposed Significant New Use Rule for Multi-walled Carbon Nanotubes; Reopening of Comment Period

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-28

    ... Proposed Significant New Use Rule for Multi-walled Carbon Nanotubes; Reopening of Comment Period AGENCY... (SNUR) for the chemical substance identified generically as multi-walled carbon nanotubes (P-08-199). In... identified generically as multi-walled carbon nanotubes as identified in Premanufacture Notice (PMN) P-08-199...

  19. 26 CFR 1.199-4 - Costs allocable to domestic production gross receipts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., natural gas, and potable water (as defined in § 1.199-3(l)) (collectively, utilities) that will generate... dollar-value pool contains QPP, qualified films, or utilities that produces DPGR and goods that do not, the taxpayer must allocate CGS attributable to that grouping or pool between DPGR and non-DPGR using a...

  20. 26 CFR 1.199-7 - Expanded affiliated groups.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Expanded affiliated groups. 1.199-7 Section 1... 2017 and 2018, B has $5 of depreciation with respect to the $50 of its additional basis that exceeds A... corporation. For each taxable year 2017 and 2018, B takes into account $5 of depreciation rather than the $0...

  1. 26 CFR 1.199-7 - Expanded affiliated groups.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Expanded affiliated groups. 1.199-7 Section 1... 2017 and 2018, B has $5 of depreciation with respect to the $50 of its additional basis that exceeds A... corporation. For each taxable year 2017 and 2018, B takes into account $5 of depreciation rather than the $0...

  2. 26 CFR 1.199-7 - Expanded affiliated groups.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Expanded affiliated groups. 1.199-7 Section 1... 2017 and 2018, B has $5 of depreciation with respect to the $50 of its additional basis that exceeds A... corporation. For each taxable year 2017 and 2018, B takes into account $5 of depreciation rather than the $0...

  3. 26 CFR 1.199-7 - Expanded affiliated groups.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Expanded affiliated groups. 1.199-7 Section 1... 2017 and 2018, B has $5 of depreciation with respect to the $50 of its additional basis that exceeds A... corporation. For each taxable year 2017 and 2018, B takes into account $5 of depreciation rather than the $0...

  4. Evaluation of Physicians and Physician Extenders: Manpower Resources

    DTIC Science & Technology

    1981-07-01

    J I..f--#.-- - -’-’, Table 9 Number of Residents on Duty Sept. 1, 1977, 1978, and 19/9 Residents orn Duty Specialty Sept 1, 19// Sept. l, 1978 $Lpt l...general 128 166 199 Aerospace rndicine 37 16 25 Occupational nedicine 29 55 70 Public health 20 26 23 Psychiatry 3,921 4,056 3,901 Child psychiatry

  5. 32 CFR 199.20 - Continued Health Care Benefit Program (CHCBP).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) § 199.20 Continued Health Care Benefit Program (CHCBP). (a) Purpose. The CHCBP is a premium based... institution of higher learning; or (2) Is incapable of self-support because of a mental or physical incapacity... retired or retainer pay of a member or former member or an annuity based on the retainer pay of the member...

  6. Nanocrystalline NiNd{sub 0.01}Fe{sub 1.99}O{sub 4} as a gas sensor

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

    Shinde, Tukaram J., E-mail: pshindetj@yahoo.co.in; Gadkari, Ashok B.; Jadhav, Sarjerao R.

    2015-06-24

    Nanocrystalline NiNd{sub 0.01}Fe{sub 1.99}O{sub 4} has been synthesized by oxalate co-precipitation method and was characterized by X-ray diffraction technique. X-ray diffraction analysis confirms the formation of single phase cubic spinel structure. Crystallite size of the ferrite lies in the nano-particle range. The gas sensing properties of nanocrystalline ferrite were studied for gases like Cl{sub 2}, LPG and C{sub 2}H{sub 5}OH. It was observed that NiNd{sub 0.01}Fe{sub 1.99}O{sub 4} is more sensitive towards chlorine followed by LPG at an operating temperature 277 °C compared to ethanol.

  7. The strong Bell inequalities: A proposed experimental test

    NASA Technical Reports Server (NTRS)

    Fry, Edward S.

    1994-01-01

    All previous experimental tests of Bell inequalities have required additional assumptions. The strong Bell inequalities (i.e. those requiring no additional assumptions) have never been tested. An experiment has been designed that can, for the first time, provide a definitive test of the strong Bell inequalities. Not only will the detector efficiency loophole be closed; but the locality condition will also be rigorously enforced. The experiment involves producing two Hg-199 atoms by a resonant Raman dissociation of a mercury dimer ((199)Hg2) that is in an electronic and nuclear spin singlet state. Bell inequalities can be tested by measuring angular momentum correlations between the spin one-half nuclei of the two Hg-199 atoms. The method used to make these latter measurements will be described.

  8. Pharmacological and protein profiling suggest venetoclax (ABT-199) as optimal partner with ibrutinib in chronic lymphocytic leukemia

    PubMed Central

    Cervantes-Gomez, Fabiola; Lamothe, Betty; Woyach, Jennifer A.; Wierda, William G.; Keating, Michael J.; Balakrishnan, Kumudha; Gandhi, Varsha

    2015-01-01

    Purpose Bruton’s tyrosine kinase (BTK) is a critical enzyme in the B-cell receptor pathway and is inhibited by ibrutinib due to covalent binding to the kinase domain. Though ibrutinib results in impressive clinical activity in chronic lymphocytic leukemia (CLL), most patients achieve only partial remission due to residual disease. We performed a pharmacologic profiling of residual circulating CLL cells from patients receiving ibrutinib to identify optimal agents that could induce cell death of these lymphocytes. Experimental design Ex vivo serial samples of CLL cells from patients on ibrutinib were obtained prior and after (weeks 2, 4, and 12) the start of treatment. These cells were incubated with PI3K inhibitors (idelalisib or IPI-145), bendamustine, additional ibrutinib, or BCL-2 antagonists (ABT-737 or ABT-199) and cell death was measured. In vitro investigations complemented ex vivo studies. Immunoblots for BTK signaling pathway and antiapoptotic proteins were performed. Results The BCL-2 antagonists, especially ABT-199, induced high cell death during ex vivo incubations. In concert with the ex vivo data, in vitro combinations also resulted highly cytotoxicity. Serial samples of CLL cells obtained before and 2, 4, 12, or 36 weeks after the start of ibrutinib showed inhibition of BTK activity and sensitivity to ABTs. Among the three BCL-2 family anti-apoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2. Conclusions Our biological and molecular results suggest that ibrutinib and ABT-199 combination should be tested clinically against CLL. PMID:25829398

  9. Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

    PubMed

    Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

    2016-01-01

    There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

  10. Interaction between ROCK II and nucleophosmin/B23 in the regulation of centrosome duplication.

    PubMed

    Ma, Zhiyong; Kanai, Masayuki; Kawamura, Kenji; Kaibuchi, Kozo; Ye, Keqiang; Fukasawa, Kenji

    2006-12-01

    Nucleophosmin (NPM)/B23 has been implicated in the regulation of centrosome duplication. NPM/B23 localizes between two centrioles in the unduplicated centrosome. Upon phosphorylation on Thr(199) by cyclin-dependent kinase 2 (CDK2)/cyclin E, the majority of centrosomal NPM/B23 dissociates from centrosomes, but some NPM/B23 phosphorylated on Thr(199) remains at centrosomes. It has been shown that Thr(199) phosphorylation of NPM/B23 is critical for the physical separation of the paired centrioles, an initial event of the centrosome duplication process. Here, we identified ROCK II kinase, an effector of Rho small GTPase, as a protein that localizes to centrosomes and physically interacts with NPM/B23. Expression of the constitutively active form of ROCK II promotes centrosome duplication, while down-regulation of ROCK II expression results in the suppression of centrosome duplication, especially delaying the initiation of centrosome duplication during the cell cycle. Moreover, ROCK II regulates centrosome duplication in its kinase and centrosome localization activity-dependent manner. We further found that ROCK II kinase activity is significantly enhanced by binding to NPM/B23 and that NPM/B23 acquires a higher binding affinity to ROCK II upon phosphorylation on Thr(199). Moreover, physical interaction between ROCK II and NPM/B23 in vivo occurs in association with CDK2/cyclin E activation and the emergence of Thr(199)-phosphorylated NPM/B23. All these findings point to ROCK II as the effector of the CDK2/cyclin E-NPM/B23 pathway in the regulation of centrosome duplication.

  11. Pharmacological and Protein Profiling Suggests Venetoclax (ABT-199) as Optimal Partner with Ibrutinib in Chronic Lymphocytic Leukemia.

    PubMed

    Cervantes-Gomez, Fabiola; Lamothe, Betty; Woyach, Jennifer A; Wierda, William G; Keating, Michael J; Balakrishnan, Kumudha; Gandhi, Varsha

    2015-08-15

    Bruton's tyrosine kinase (BTK) is a critical enzyme in the B-cell receptor pathway and is inhibited by ibrutinib due to covalent binding to the kinase domain. Though ibrutinib results in impressive clinical activity in chronic lymphocytic leukemia (CLL), most patients achieve only partial remission due to residual disease. We performed a pharmacologic profiling of residual circulating CLL cells from patients receiving ibrutinib to identify optimal agents that could induce cell death of these lymphocytes. Ex vivo serial samples of CLL cells from patients on ibrutinib were obtained prior and after (weeks 2, 4, and 12) the start of treatment. These cells were incubated with PI3K inhibitors (idelalisib or IPI-145), bendamustine, additional ibrutinib, or BCL-2 antagonists (ABT-737 or ABT-199), and cell death was measured. In vitro investigations complemented ex vivo studies. Immunoblots for BTK signaling pathway and antiapoptotic proteins were performed. The BCL-2 antagonists, especially ABT-199, induced high cell death during ex vivo incubations. In concert with the ex vivo data, in vitro combinations also resulted in high cytotoxicity. Serial samples of CLL cells obtained before and 2, 4, 12, or 36 weeks after the start of ibrutinib showed inhibition of BTK activity and sensitivity to ABTs. Among the three BCL-2 family antiapoptotic proteins that are overexpressed in CLL, levels of MCL-1 and BCL-XL were decreased after ibrutinib while ABT-199 selectively antagonizes BCL-2. Our biologic and molecular results suggest that ibrutinib and ABT-199 combination should be tested clinically against CLL. ©2015 American Association for Cancer Research.

  12. 46 CFR 199.630 - Alternatives for passenger vessels in a specified service.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... applies if the vessel operates in shallow water not more than 3 miles from shore where the vessel cannot sink deep enough to submerge the topmost deck. 5 Alternative applies if the vessel operates on... requirements for survival craft in § 199.201(b) if the vessel operates— (1) On a route that is in shallow water...

  13. 75 FR 59173 - TRICARE: Elimination of Copayments for Authorized Preventive Services for Certain TRICARE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ...'' section that are not truly preventive but are more evaluative in nature in the ``Special Benefit Information'' Section of 32 CFR 199.4(e) and add a definition of ``evaluative'' services in 32 CFR 199.2. VII...) is revised to add a definition for evaluative services. The purpose of this is to make a distinction...

  14. Overview to the north from near ordnance warehouse A199, showing ...

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

    Overview to the north from near ordnance warehouse A-199, showing water tank 188-A, 188-B behind, magazine A-211 at center, and magazine A-212 at far right. The city of Vallejo is in the distance. - Mare Island Naval Shipyard, Fresh Water Tanks, East of Mesa Road & north of Kieper Road, Vallejo, Solano County, CA

  15. 20 CFR 1002.199 - What priority must the employer follow if two or more returning employees are entitled to...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What priority must the employer follow if two... ACT OF 1994 Reemployment Rights and Benefits Reemployment Position § 1002.199 What priority must the... service has the first priority on reemployment in that position. The remaining employee (or employees) is...

  16. 26 CFR 1.199-1 - Income attributable to domestic production activities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... under section 199 is not taken into account in computing any net operating loss or the amount of any net... from the sale of gasoline refined by X within the United States and the sale of refined gasoline that X... gasoline refined by X within the United States (that qualify as DPGR if all the other requirements of § 1...

  17. 26 CFR 1.199-1 - Income attributable to domestic production activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... under section 199 is not taken into account in computing any net operating loss or the amount of any net... from the sale of gasoline refined by X within the United States and the sale of refined gasoline that X... gasoline refined by X within the United States (that qualify as DPGR if all the other requirements of § 1...

  18. 26 CFR 1.199-1 - Income attributable to domestic production activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... under section 199 is not taken into account in computing any net operating loss or the amount of any net... from the sale of gasoline refined by X within the United States and the sale of refined gasoline that X... gasoline refined by X within the United States (that qualify as DPGR if all the other requirements of § 1...

  19. 26 CFR 1.199-1 - Income attributable to domestic production activities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... under section 199 is not taken into account in computing any net operating loss or the amount of any net... from the sale of gasoline refined by X within the United States and the sale of refined gasoline that X... gasoline refined by X within the United States (that qualify as DPGR if all the other requirements of § 1...

  20. Relationship between serum calcium and CA 19-9 levels in colorectal cancer

    PubMed Central

    Fuszek, Peter; Lakatos, Peter; Tabak, Adam; Papp, Janos; Nagy, Zsolt; Takacs, Istvan; Horvath, Henrik Csaba; Lakatos, Peter Laszlo; Speer, Gabor

    2004-01-01

    AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n = 32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25 (OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer. PMID:15222030

  1. [Analysis of the dilution deviation in CA19-9 measurement].

    PubMed

    Hanada, Hiroyuki; Takeoka, Keiko; Nomura, Tomoko; Moriyama, Takanori; Kanakura, Yuzuru

    2005-04-01

    CA19-9 widely used as a tumor marker of the pancreas and a bile duct. There are a number of reports which describes the measured value discrepancies between RIA and non-RIA kits. RIA results also have shown lack of the linearity over 70 U/ml when the samples are diluted. The pH condition at assay reaction for RIA had been suggested as the major reason, it has been denied by the results from the same pH condition at assay reaction used by COBAS CORE CA19-9 EIA II. On the other hand, the lack of RIA antibody titer is indicated for the discordant results by changing the sample volume to reagent volume ratio in the reaction. Our further investigation also indicates that the specific Lewis blood type, i.e. Le (a-b+), shows the linearity issues by RIA. The discrepancies are not caused by the reaction pH, but the amount of the antibody used in the RIA kit is closely associated. Considering the CA19-9 antibody nature used in RIA kit, which covers broad molecular range, users need to pay more attention to setting up each laboratory's measuring range.

  2. Linear Optimization of Frequency Spectrum Assignments Across System

    DTIC Science & Technology

    2016-03-01

    DNT_0_0 1200 1 r19 DNT_0_0 1200 1 r45 DNT_0_0 1400 1 r20 RAD_LOW 3050 1 r46 DNT_0_0 1600 1 r21 TX_LOW_1_2 1201 1 r47 DNT_0_0 1603 1 r21 RX_LOW_2_1...0  1400  1401  1  1  200  199  CM7  R46  1  1  0  0  0  1600  1601  1  1  200  199  DT3  R47  1  1  0  0  0  1603   1604  1  1  200  199  DT3  R48  1

  3. A Distinct Magnetic Isotope Effect Measured in Atmospheric Mercury in Epiphytes

    NASA Astrophysics Data System (ADS)

    Ghosh, S.; Odom, A. L.

    2007-12-01

    Due to the importance of Mercury as an environmental contaminant, mercury cycling in the atmosphere has been extensively studied. However, there still remain uncertainties in the relative amounts of natural and anthropogenic emissions, atmospheric deposition rates as well as the spatial variation of atmospheric mercury. Part of a study to determine the isotopic composition of mercury deposited from the atmosphere has involved the use of epiphytes as monitors. The greatest advantage of such natural monitors is that a widespread, high-density network is possible at low cost. One of the disadvantages at present is that these monitors likely contain different mercury species (for example both gaseous, elemental mercury trapped by adsorption and Hg (II) by wet deposition). The project began with the understanding that biochemical reactions involving metallothioneins within the epiphytes might have produced an isotopic effect. One such regional network was composed of samples of Tillandsia usenoides (common name: Spanish moss) collected along the eastern Coastal Plain of the U.S. from northern Florida to North Carolina. The isotopic composition of a sample is expressed as permil deviations from a standard. The deviations are defined as δAHg = \\left(\\frac{Rsample}{Rstd}-1 \\right)1000 ‰ , where A represents the atomic mass number. R=\\frac{AHg}{202Hg} were measured for the isotopes 198Hg, 199Hg, 200Hg, 201Hg, 202Hg and 204Hg relative to the mercury standard SRM NIST 3133, by a standard-sample bracketing technique. For all samples, the delta values of the even-N plotted against atomic mass numbers define a linear curve. For the odd-N isotopes, δ199Hg and δ201Hg deviate from this mass-dependent fractionation (MDF) relationship and indicate a mass-independent fractionation (MIF) effect and a negative anomaly, i.e. a depletion in 199Hg and 201Hg relative to the even-N isotopes. These deviations are expressed as Δ199Hg = δ199Hgtotal - δ199HgMDF. A Δ201Hg/Δ199Hg ratio of 1.11 is predicted by isotope fractionation due to the Magnetic Isotope Effect (MIE), because 1.11 is the ratio of the magnetic moments of the two odd-N isotopes. A plot of Δ199Hg versus Δ201Hg values obtained reveals a striking pattern. All samples plot well within analytical uncertainly along a straight line passing through zero and having a slope of 1.11. Based on thermodynamic principles, some have argued that nuclear spin effects are quite insignificant in producing isotopic fractionation. However the MIE is a kinetic one in which those isotopes with non-zero magnetic moments effect the rates of recombination of free radical pairs by nuclear-electron hyperfine interaction and can become enriched or depleted in either reactants or products. In the samples studied here, the nuclear spin is far more important than either nuclear mass or nuclear volume in effecting isotopic fractionation of Mercury.

  4. Carnitine-acylcarnitine translocase deficiency with c.199-10 T>G and novel c.1A>G mutation

    PubMed Central

    Yan, Hui-ming; Hu, Hao; Ahmed, Aisha; Feng, Bing-bing; Liu, Jing; Jia, Zheng-jun; Wang, Hua

    2017-01-01

    Abstract Rationale: Carnitine-acylcarnitine translocate deficiency (CACTD) is a rare and life-threatening, autosomal recessive disorder of fatty acid β-oxidation characterized by hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy, liver dysfunction, and muscle weakness; culminating in early death. To date, CACTD cases screened from the Chinese mainland population, especially patient with compound heterozygote with c.199-10T>G and a novel c.1A>G mutation in the SLC25A20 gene has never been described. Patient concerns: Herein, we report 2 neonatal cases of CACTD identified from the mainland China. These 2 patients were presented with severe metabolic crisis and their clinical conditions deteriorate rapidly and both died of cardiorespiratory collapse in the first week of life. We present the clinical and biochemical features of 2 probands and a brief literature review of previously reported CACTD cases with the c.199-10T>G mutation. Diagnoses: The acylcarnitine profiles by tandem-mass-spectrometry and the mutation analysis of SLC25A20 gene confirmed the diagnosis of CACTD in both patients. Mutation analysis demonstrated that patient No. 1 was homozygous for c.199-10T>G mutation, while patient No. 2 was a compound heterozygote for 2 mutations, a maternally-inherited c.199-10T>G and a paternally-inherited, novel c.1A>G mutation. Interventions: Both patients were treated with an aggressive treatment regimen include high glucose and arginine infusion, respiratory, and circulatory support. Outcomes: The first proband died 3 days after delivery due to sudden cardiac arrest. The second patient's clinical condition, at one time, was improved by high glucose infusion, intravenous arginine, and circulatory support. However, the patient failed to wean from mechanical ventilation. Unfortunately, her parents refused further treatment due to fear of financial burdens. The patient died of congestive heart failure in the 6th day of life. Lessons: We report the first 2 cases of CACTD identified from the mainland China. Apart from a founder mutation c.199-10T>G, we identified a novel c.1A>G mutation. Patients with CACTD with a genotype of c.199-10T>G mutation usually presents with a severe clinical phenotype. Early recognition and appropriate treatment is crucial in this highly lethal disorder. This case series highlights the importance of screening for metabolic diseases including CACTD in cases of sudden infant death and unexplained abrupt clinical deterioration in the early neonatal period. PMID:29137068

  5. In Vivo Mass-independent Fractionation of Mercury Isotopes in Fish

    NASA Astrophysics Data System (ADS)

    Das, R.; Odom, L. A.

    2008-12-01

    Recent experimental work and analyses of natural samples have revealed both mass-dependent and mass- independent isotope fractionation effects in mercury. These findings portend new avenues toward understanding the global mercury cycle. It has been shown experimentally that photo reduction of Hg+2 and methylmercury in water with concomitant release of the reduced, gaseous species Hg° results in the residual methylmercury possessing a mass-independent isotope effect. This effect is a relative enrichment of isotopes 199Hg and 201Hg over the even mass number isotopes when compared to the mercury standard NIST SRM3133. Large mass independent fractionation (MIF) effects (Δ199Hg values of a few ‰) have been found in mercury in fish and interpreted as isotope effects inherited from the water. To evaluate the possibility that MIF might be produced within the fish, we have analyzed 38 samples that include zooplankton and twelve different species of fish from a single lake collected over a 2-month time period for mercury isotopic compositions. Trophic levels of the same fish specimens had previously been determined from stomach contents and nitrogen isotopes. Zooplankton in the lake contain mercury with Δ199Hg and Δ201Hg values of +0.43 (±0.07) and +0.44 (±0.07) respectively. Among the fish species there is a striking correspondence between trophic level and Δ199Hg and Δ201Hg values for primary, secondary, and tertiary consumers. The Δ199Hg values ranges over ~1‰ from ~+0.4 in zooplankton, juvenile bluegill and several other small fishes to Δ199Hg = + 1.36 for the Florida gar that is the top predator fish in the lake. These observations indicate that the MIF effect, rather than being an artifact of the water column is produced in vivo. Partial separation of 199Hg and 201Hg from isotopes of even neutron number can be achieved by the magnetic isotope effect in reactions involving sufficiently long-lived intermediate free radicals, where nuclear - electron hyperfine coupling influence radical recombination and thus reaction kinetics. There is experimental evidence that this can occur during the inhibiting activity of methylmercury on creatine kinase. Here the enzyme provides the free radicals. Previously, reports of chemical mass- independent fractionation of isotopes in nature have involved gas phase reactions and largely explained by photolysis. It now seems that isotopic MIF can occur during metabolic processes as well.

  6. miR-199a and miR-497 Are Associated with Better Overall Survival due to Increased Chemosensitivity in Diffuse Large B-Cell Lymphoma Patients

    PubMed Central

    Troppan, Katharina; Wenzl, Kerstin; Pichler, Martin; Pursche, Beata; Schwarzenbacher, Daniela; Feichtinger, Julia; Thallinger, Gerhard G.; Beham-Schmid, Christine; Neumeister, Peter; Deutsch, Alexander

    2015-01-01

    Micro-RNAs (miRNAs) are short non-coding single-stranded RNA molecules regulating gene expression at the post-transcriptional level. miRNAs are involved in cell development, differentiation, apoptosis, and proliferation. miRNAs can either function as tumor suppressor genes or oncogenes in various important pathways. The expression of specific miRNAs has been identified to correlate with tumor prognosis. For miRNA expression analysis real-time PCR on 81 samples was performed, including 63 diffuse large B-cell lymphoma (DLBCL, 15 of germinal center B-cell like subtype, 17 non germinal center B-cell, 23 transformed, and eight unclassified) and 18 controls, including nine peripheral B-cells, 5 germinal-center B-cells, four lymphadenitis samples, and 4 lymphoma cell lines (RI-1, SUDHL4, Karpas, U2932). Expression levels of a panel of 11 miRNAs that have been previously involved in other types of cancer (miR-15b_2, miR-16_1*, miR-16_2, miR-16_2*, miR-27a, miR-27a*, miR-98-1, miR-103a, miR-185, miR-199a, and miR-497) were measured and correlated with clinical data. Furthermore, cell lines, lacking miR-199a and miR-497 expression, were electroporated with the two respective miRNAs and treated with standard immunochemotherapy routinely used in patients with DLBCL, followed by functional analyses including cell count and apoptosis assays. Seven miRNAs (miR-16_1*, miR-16_2*, miR-27a, miR-103, miR-185, miR-199, and miR-497) were statistically significantly up-regulated in DLBCL compared to normal germinal cells. However, high expression of miR-497 or miR-199a was associated with better overall survival (p = 0.042 and p = 0.007). Overexpression of miR-199a and miR-497 led to a statistically significant decrease in viable cells in a dose-dependent fashion after exposure to rituximab and various chemotherapeutics relevant in multi-agent lymphoma therapy. Our data indicate that elevated miR-199a and miR-497 levels are associated with improved survival in aggressive lymphoma patients most likely by modifying drug sensitivity to immunochemotherapy. This functional impairment may serve as a potential novel therapeutic target in future treatment of patients with DLBCL. PMID:26251897

  7. Long noncoding RNA H19 upregulates vascular endothelial growth factor A to enhance mesenchymal stem cells survival and angiogenic capacity by inhibiting miR-199a-5p.

    PubMed

    Hou, Jingying; Wang, Lingyun; Wu, Quanhua; Zheng, Guanghui; Long, Huibao; Wu, Hao; Zhou, Changqing; Guo, Tianzhu; Zhong, Tingting; Wang, Lei; Chen, Xuxiang; Wang, Tong

    2018-04-19

    Currently, the overall therapeutic efficiency of mesenchymal stem cells (MSCs) transplantation for the treatment of cardiovascular disease is not satisfactory. The low viability and angiogenic capacity of the implanted cells in the local infarct tissues restrict their further application. Evidence shows that long noncoding RNA H19 (lncRNA-H19) mediates cell survival and angiogenesis. Additionally, it is also involved in MSCs biological activities. This study aimed to explore the functional role of lncRNA-H19 in MSCs survival and angiogenic capacity as well as the underlying mechanism. MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells at the third passage were divided into the following groups: MSCs+H19, MSCs+H19 NC, MSCs+si-H19, MSCs+si-H19 NC and MSCs. The MSCs+H19 and MSCs+H19 NC groups were transfected with lncRNA-H19 and lncRNA-H19 scramble RNA respectively. The MSCs+si-H19 and MSCs+si-H19 NC groups were transfected with lncRNA-H19 siRNA and lncRNA-H19 siRNA scramble respectively. MSCs were used as the blank control. All groups were exposed to normoxia (20% O 2 ) and hypoxia (1% O 2 )/serum deprivation (H/SD) conditions for 24 h. Cell proliferation, apoptosis and vascular densities were assessed. Bioinformatics and dual luciferase reporter assay were performed. Relevant biomarkers were detected in different experimental groups. Overexpression of lncRNA-H19 improved survival and angiogenic capacity of MSCs under both normoxia and H/SD conditions, whereas its knockdown impaired cell viability and their angiogenic potential. MicroRNA-199a-5p (miR-199a-5p) targeted and downregulated vascular endothelial growth factor A (VEGFA). MiR-199a-5p was a target of lncRNA-H19. LncRNA-H19 transfection led to a decreased level of miR-199a-5p, accompanied with an elevated expression of VEGFA. However, both miR-199a-5p and VEGFA presented inverse alterations in the condition of lncRNA-H19 knockdown. LncRNA-H19 enhanced MSCs survival and their angiogenic potential in vitro. It could directly upregulate VEGFA expression by inhibiting miR-199a-5p as a competing endogenous RNA. This mechanism contributes to a better understanding of MSCs biological activities and provides new insights for cell therapy based on MSCs transplantation.

  8. Carnitine-acylcarnitine translocase deficiency with c.199-10 T>G and novel c.1A>G mutation: Two case reports and brief literature review.

    PubMed

    Yan, Hui-Ming; Hu, Hao; Ahmed, Aisha; Feng, Bing-Bing; Liu, Jing; Jia, Zheng-Jun; Wang, Hua

    2017-11-01

    Carnitine-acylcarnitine translocate deficiency (CACTD) is a rare and life-threatening, autosomal recessive disorder of fatty acid β-oxidation characterized by hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy, liver dysfunction, and muscle weakness; culminating in early death. To date, CACTD cases screened from the Chinese mainland population, especially patient with compound heterozygote with c.199-10T>G and a novel c.1A>G mutation in the SLC25A20 gene has never been described. Herein, we report 2 neonatal cases of CACTD identified from the mainland China. These 2 patients were presented with severe metabolic crisis and their clinical conditions deteriorate rapidly and both died of cardiorespiratory collapse in the first week of life. We present the clinical and biochemical features of 2 probands and a brief literature review of previously reported CACTD cases with the c.199-10T>G mutation. The acylcarnitine profiles by tandem-mass-spectrometry and the mutation analysis of SLC25A20 gene confirmed the diagnosis of CACTD in both patients. Mutation analysis demonstrated that patient No. 1 was homozygous for c.199-10T>G mutation, while patient No. 2 was a compound heterozygote for 2 mutations, a maternally-inherited c.199-10T>G and a paternally-inherited, novel c.1A>G mutation. Both patients were treated with an aggressive treatment regimen include high glucose and arginine infusion, respiratory, and circulatory support. The first proband died 3 days after delivery due to sudden cardiac arrest. The second patient's clinical condition, at one time, was improved by high glucose infusion, intravenous arginine, and circulatory support. However, the patient failed to wean from mechanical ventilation. Unfortunately, her parents refused further treatment due to fear of financial burdens. The patient died of congestive heart failure in the 6th day of life. We report the first 2 cases of CACTD identified from the mainland China. Apart from a founder mutation c.199-10T>G, we identified a novel c.1A>G mutation. Patients with CACTD with a genotype of c.199-10T>G mutation usually presents with a severe clinical phenotype. Early recognition and appropriate treatment is crucial in this highly lethal disorder. This case series highlights the importance of screening for metabolic diseases including CACTD in cases of sudden infant death and unexplained abrupt clinical deterioration in the early neonatal period.

  9. 29 CFR 1910.125 - Additional requirements for dipping and coating operations that use flammable liquids or liquids...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... that use flammable liquids or liquids with flashpoints greater than 199.4 °F (93 °C). 1910.125... flammable liquids or liquids with flashpoints greater than 199.4 °F (93 °C). If you use flammable liquids... provide: (i) Manual fire extinguishers that are suitable for flammable and combustible liquid fires and...

  10. 29 CFR 1910.125 - Additional requirements for dipping and coating operations that use flammable liquids or liquids...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... that use flammable liquids or liquids with flashpoints greater than 199.4 °F (93 °C). 1910.125... flammable liquids or liquids with flashpoints greater than 199.4 °F (93 °C). If you use flammable liquids... provide: (i) Manual fire extinguishers that are suitable for flammable and combustible liquid fires and...

  11. 75 FR 16837 - In the Matter of Certain Integrated Circuits, Chipsets, and Products Containing Same Including...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-02

    .... 1337, on behalf of Freescale Semiconductor, Inc. of Austin, Texas. A letter supplementing the complaint...,715,014; and 7,199,306. The complaint further alleges that an industry in the United States exists as...,715,014; and claims 1, 6, 11, and 13-16 of U.S. Patent No. 7,199,306, and whether an industry in the...

  12. JPRS Report, China, Handbook of Military Knowledge for Commanders

    DTIC Science & Technology

    1988-03-07

    Chemical and Biological Weapons Chapter I Nuclear Weapons (178) A. Summary Statement on Nuclear Weapons (178) 1. Basic Principles of Nuclear...199) 1. Basic Principles of Protection Against Nuclear, Chemical and Biological Weapons* (199) 2. Maior Actions For Protection Against Nuclear...people’s bodies through the digestive tract. Skin contact. Biological warfare agents may enter the body directly through the skin , mucous membranes or

  13. Adult human pancreas-derived cells expressing stage-specific embryonic antigen 4 differentiate into Sox9-expressing and Ngn3-expressing pancreatic ducts in vivo.

    PubMed

    Lee, Song; Lee, Chan Mi; Kim, Song Cheol

    2016-11-11

    Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. Here, we examined the characteristics and lineage-specific differentiation capacity of SSEA-4 + cells. Human adult partial pancreas tissues were obtained from different donors and cultured in vitro. SSEA-4 + and CA19-9 + cells were isolated from adult human pancreas exocrine cells using magnetic-activated cell sorting, and gene expression was validated by quantitative polymerase chain reaction. To confirm in-vivo differentiation, SSEA-4 + and CA19-9 + cells were transplanted into the dorsal subcutaneous region of mice. Finally, morphological features of differentiated areas were confirmed by immunostaining and morphometric analysis. SSEA-4-expressing cells were detected in isolated pancreas exocrine cells from adult humans. These SSEA-4 + cells exhibited coexpression of CA19-9, a marker of pancreatic duct cells, but not amylase expression, as shown by immunostaining and flow cytometry. SSEA-4 + cells exhibited higher relative expression of Oct4, Nanog, Klf4, Sox2, and c-Myc mRNAs than CA19-9 + cells. Pancreatic intralobular ducts (PIDs) were generated from SSEA-4 + or CA19-9 + cells in vivo at 5 weeks after transplantation. However, newly formed PIDs from CA19-9 + cells were less abundant and showed an incomplete PID morphology. In contrast, newly formed PIDs from SSEA-4 + cells were abundant in the transplanted area and showed a crowded morphology, typical of PIDs. Sox9 and Ngn3, key transcription factors associated with pancreatic development and regeneration, were expressed in PIDs from SSEA-4 + cells. SSEA-4-expressing cells in the adult human pancreas may have the potential for regeneration of the pancreas and may be used as a source of stem/progenitor cells for pancreatic cell lineage-specific differentiation.

  14. Detection of K-ras gene mutations in feces by magnetic nanoprobe in patients with pancreatic cancer: A preliminary study.

    PubMed

    Wang, Xiaoguang; Wang, Jingshuai; Chen, Fei; Zhong, Zhengxiang; Qi, Lifeng

    2018-01-01

    The present study aimed to investigate the feasibility and effectiveness of detecting K-ras mutation by using magnetic nanoparticles in fecal samples of patients with pancreatic cancer at different stages. The novel methodology of K-ras mutation detection was compared to the existing methodology of cancer antigen (CA)19-9 examination. Patients with pancreatic cancer (n=88), pancreatic benign diseases who displayed chronic pancreatitis (n=35), pancreatic mucinous cyst neoplasms (n=10) and pancreatic serous cyst (n=9) admitted to the Department of Surgery, Jiaxing Second Hospital were enrolled in the present study. Fecal samples were collected from all patients, DNA was extracted and magnetic nanoprobe was then used to detect K-ras mutation. The results obtained using the novel magnetic nanoprobe detection technique showed a K-ras mutation rate of 81.8% (72/88) in the patients with pancreatic cancer and 18.5% (10/54) in patients with pancreatic benign diseases. In patients with pancreatic cancer, the K-ras mutation rate was comparable in stages I + IIA and IIB + III + IV (78.9 vs. 84.0%; P>0.05). The sensitivity and specificity of K-ras mutation for detection of pancreatic cancer was 81.8 and 81.5%, respectively. Sixty-eight pancreatic cancer patients had >37 U/ml CA99 with a sensitivity and specificity for pancreatic cancer detection of 77.3 and 77.8%, which was not significantly lower than detection by the fecal K-ras mutations (P>0.05). Combinational detection of fecal K-ras mutations and serum CA19-9 significantly increased the sensitivity regarding pancreatic cancer detection to 97.7% (P<0.05), while the specificity was not enhanced (80.9%; P>0.05) compared with fecal K-ras mutations or CA19-9 alone. The findings showed that the magnetic nanoprobe is able to detect fecal K-ras mutations in different stages of pancreatic cancer, with comparable sensitivity and specificity to CA19-9 examination for differentiating pancreatic cancer. Furthermore, combined detection of CA19-9 and K-ras mutations has enhanced sensitivity compared with CA19-9 alone.

  15. Genetic Variants of APOC3 Promoter and HLA-B Genes in an HIV Infected Cohort in Northern South Africa: A Pilot Study

    PubMed Central

    Masebe, Tracy; Bessong, Pascal Obong; Ndip, Roland Ndip; Meyer, Debra

    2014-01-01

    Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of −482 (p = 1; χ2 = 0.00001) or −455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the −455C genotype, but not in males for the −455T genotype. Viral load decreases were significant with the −455C and −482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders. PMID:24972136

  16. Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis).

    PubMed

    Bagaria, Bhawna; Sood, Sadhna; Sharma, Rameshwaram; Lalwani, Soniya

    2013-09-01

    To determine the clinical serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic (ROC) curves were plotted. Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined: in esophageal cancer, sensitivity=28%, negative predictive value (NPV)=61.72%, and AUC=0.742 
(SE=0.05), with a significance level of P<0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 (SE=0.05), with a significance level of P<0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 
(SE=0.04), with a significance level of P<0.0001. The sensitivity of CA19-9 was also evaluated: in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 (SE =0.05), with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 (SE =0.05), with a significance level of P<0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.580 (SE =0.05), with a significance level of P=0.1670. The following were the sensitivities of CEA/CA19-9 combined: in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 (95% CI: 0.0159-0.322); gastric cancer, sensitivity=58%, NPV=70.42%, SE=0.072 (95% CI: -0.0866-0.198); and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 (95% CI: 0.137-0.415). CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

  17. Changing Relationship Growth Belief: Intrapersonal and Interpersonal Consequences of Compassionate Goals

    PubMed Central

    Canevello, Amy; Crocker, Jennifer

    2010-01-01

    The belief that difficulties can lead to growth in relationships, or growth belief, has consequences for relationships (e.g., Knee, 1998). But what predicts change in this belief? We hypothesized that compassionate goals to support others (Crocker & Canevello, 2008) predict increased growth belief through increased need satisfaction. In Study 1, 199 college freshmen reported their friendship growth belief and goals. In Study 2, 65 roommate pairs reported their roommate growth belief, goals, and need satisfaction. Across studies, compassionate goals predicted increased growth belief. In Study 2, goals predicted increased perceived mutual need satisfaction, which predicted increased growth belief. Additionally, partners’ compassionate goals predicted actors’ increased growth belief. Results suggest that growth beliefs are shaped by goals – own and others’. PMID:21949478

  18. New 2',6'-dimethyl-L-tyrosine (Dmt) opioid peptidomimetics based on the Aba-Gly scaffold. Development of unique mu-opioid receptor ligands.

    PubMed

    Ballet, Steven; Salvadori, Severo; Trapella, Claudio; Bryant, Sharon D; Jinsmaa, Yunden; Lazarus, Lawrence H; Negri, Lucia; Giannini, Elisa; Lattanzi, Roberta; Tourwé, Dirk; Balboni, Gianfranco

    2006-06-29

    The Aba-Gly scaffold, incorporated into Dmt-Tic ligands (H-Dmt-Tic-Gly-NH-CH2-Ph, H-Dmt-Tic-Gly-NH-Ph, H-Dmt-Tic-NH-CH2-Bid), exhibited mixed micro/delta or delta opioid receptor activities with micro agonism. Substitution of Tic by Aba-Gly coupled to -NH-CH2-Ph (1), -NH-Ph (2), or -Bid (Bid=1H-benzimidazole-2-yl) (3) shifted affinity (Ki(micro)=0.46, 1.48, and 19.9 nM, respectively), selectivity, and bioactivity to micro-opioid receptors. These compounds represent templates for a new class of lead opioid agonists that are easily synthesized and suitable for therapeutic pain relief.

  19. 1. West portal of Snowshed 29, contextual view to east, ...

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

    1. West portal of Snowshed 29, contextual view to east, 135mm lens. This is perhaps the last section of timber snowshed on this line. Integral with the east end of Tunnel 41, Snowshed 29 provides protection leading to the west portal of the tunnel. The snowshed today consists of (west to east) 199 feet of timber type T4 shed built in 1954, 365 feet of timber type T7 built in 1954, 85 feet of timber type T1 built in 1951, four feet of timber type T7 built in 1925 concurrent with Tunnel 41, and 41 feet of recent prefabricated concrete panel shed. - Central Pacific Transcontinental Railroad, Tunnel No. 41, Milepost 193.3, Donner, Placer County, CA

  20. Evidence for a kinetic heterogeneity in ligand binding to R-state haemoglobin Kempsey [Asp-G1(99) beta----Asn].

    PubMed Central

    Coletta, M; Brittain, T; Brunori, M

    1986-01-01

    Thermodynamic and kinetic properties of O2 and CO binding to haemoglobin (Hb) Kempsey [Asp-G1(99) beta----Asn] were investigated and the activation parameters for the two ligands were determined. At every temperature the O2-binding isotherms display a weak co-operativity, n ranging between 1.1 and 1.2, and dissociation kinetics show a single-exponential behaviour. O2-binding kinetics were studied at 25 degrees C by temperature jump and are characterized at each saturation (from Y = 0.31 to Y = 1.0) by two processes, a fast bimolecular one and a slow monomolecular one (tau -1 = 20 s-1), which contributes to approx. 30% of the whole relaxation amplitude at every Y. CO-binding kinetics to Hb Kempsey were followed at several temperatures by flash photolysis and stopped flow. The process is biphasic, as reported elsewhere [Bunn, Wohl, Bradley, Cooley & Gibson (1974) J. Biol. Chem. 249, 7402-7409], and the relative contributions of the two bimolecular rates to the whole process are only slightly affected by temperature. On taking account for the fraction of dimers at every protein concentration, the slow phase corresponds to approx. 50% of the ligand binding to tetramers. Correlation of these results with previous spectroscopic data leads to the hypothesis that the biphasic time course of CO binding may be attributed to alpha/beta heterogeneity of the R-state of tetrameric Hb Kempsey. PMID:3800943

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